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Sodium phosphorus: persistent but surmountable hurdles in the management of nutrition in chronic kidney disease

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persistent but surmountable hurdles in the management of nutrition in chronic kidney disease

Abstract

Sodium and phosphorus-based food additives are among the most commonly consumed nutrients in the world. This is because both have diverse applications in processed food manufacturing, leading to their widespread utilization by the food industry. Since most foods are naturally low in salt, sodium additives almost completely account for the excessive consumption of sodium throughout the world. Similarly, phosphorus additives represent a major and “hidden” phosphorus load in modern diets. These factors pose a major barrier to successfully lowering sodium or phosphorus intake in patients with chronic kidney disease. As such, any serious effort to reduce sodium or phosphorus consumption will require reductions in the use of these additives by the food industry. The current regulatory environment governing the use of food additives does not favor this goal, however, in large part because these additives have historically been classified as generally safe for public consumption. To overcome these barriers, coordinated efforts will be needed to demonstrate that high intakes of these additives are not safe for public consumption and as such, should be subject to greater regulatory scrutiny.

Keywords: nutrition, diet, sodium, phosphorus, chronic kidney disease

INTRODUCTION

Sodium-based food additives are among the most abundantly consumed nutrients in the world. This is because sodium salts are not only effective anti-spoilage agents, they can also serve as relatively cheap taste enhancers in a variety of foods. As a result, sodium additives are heavily utilized in processed foods, accounting for the vast majority of the excess sodium consumed throughout the world. Though discovered and utilized as a food additive later than sodium, phosphorus-based food additives have taken on a similar wide berth of uses, including as food preservatives and taste enhancers. Like sodium, phosphorus additives have become nearly indispensable in food manufacturing, substantially augmenting the phosphorus content of processed foods. The public health consequences of these trends have been well-publicized, particularly with respect to the link between excess dietary sodium intake and the increasing prevalence and severity of hypertension in both the developed and developing world. These trends have more ominous implications for millions of individuals living with chronic kidney disease (CKD), who have reduced capacity to excrete even normal dietary sodium and phosphorus loads. This review will focus on the impact of sodium- and phosphorus-based food additives on total daily intake of sodium and phosphorus in contemporary diets, the special implications this may have for individuals with chronic kidney disease, and potential strategies for reducing the consumption of sodium and phosphorus-based food additives in CKD patients.

Sodium Additives

Sodium-based food additives were introduced into the human diet somewhere between 5,000 to 10,000 years ago when they were found to retard the spoilage of poultry and meat products. 1 This discovery revolutionized the capacity for early societies to preserve meat for personal consumption and/or trade purposes, markedly increasing the use of sodium in a variety of foodstuffs. The importance of this discovery is evident from historical records which show that access to salt was a cherished commodity in early societies, on par with the finest measures of wealth and social standing, and in some cases, used as a form of currency.1, 2

Historically, the primary reason to add sodium to foods was as a method for food preservation,1 based largely upon sodium’s antimicrobial properties.3 With the advent of refrigeration and other advances in food preservation, the primary motivations evolved beyond just anti-spoilage agents to enhancing the taste and palatability of foods.4 Salt (hereby referring to sodium chloride) has a number of desirable effects on foodstuffs, including improving the intensity of flavor and augmenting the overall perception of product thickness and fullness. 5, 6 Consistent with this, there is remarkable congruity with respect to the excessive levels of sodium consumption across countries with very different culinary traditions,7, 8 suggesting a strong salt preference in human populations.9 Along with its preservative and taste-enhancing effects, salt is also commonly used in the fermentation, emulsification, leavening, and enhancement of foods,10 contributing to very high levels of salt usage by the food manufacturing industry.

Since most food items contain relatively low amounts of sodium naturally, the introduction of sodium additives into human food supplies effectively increased the average daily consumption of sodium from less than 400 mg per day in pre-historic times to an average of 4,000 mg per day in modern times, far above current recommendations for daily intake ().8, 11 It is estimated that only 10% of daily salt intake in Western populations comes from natural sources, whereas 75% comes from salt added to processed foods by manufacturers, and the remaining 15% from salt added during cooking or other discretionary uses. 12 While Asian populations manifest similarly high levels of added sodium intake,8 there is important variability in the sources of added sodium in Eastern vs. Western countries. This was perhaps best demonstrated in the INTERMAP study, a large international cooperative study that estimated the quantity and sources of sodium intake in 4,680 individuals 40 to 59 years of age from Japan, the People’s Republic of China, the United Kingdom and the United States.13 This study showed that the majority of sodium intake in the United Kingdom and the United States came from processed breads, cereals, grains, meats, sauces and canned items with only a very small fraction (5 – 10%) coming from salt added in home cooking or at the table.8 In contrast, the majority of salt intake in Japan came from soy sauce, salted fruits and vegetables, miso soup, and fish, whereas in China, the vast majority of sodium intake (76%) came from salt added during home cooking or at the table. These differences highlight the importance of regional factors in determining the sources of sodium intake in the developed and developing world.

Table 1

United States Department of Agriculture Dietary Reference Intakes for sodium and phosphorus intake by age group

Nutrient Age RDA/AI (grams/day) TUL (grams/day)
Sodium66 0-6 months 0.12* ND
7-12 months 0. 37* ND
1-3 years 1.0* 1.5
4-8 years 1.2* 1.9
9-50 years 1.5* 2.3
50-70 years 1. 3* 2.3
> 70 years 1.2* 2.3
Phosphorus37 0-6 months 0.1* ND
7-12 months 0.28* ND
1-3 years 0. 46 3.0
4-8 years 0.5 3.0
9-13 years 1.25 4.0
14-18 years 1.25 4.0
> 18 years 0. 7 3.0
Health Impact of Sodium Additives in Individuals with Chronic Kidney Disease

Large observational studies have shown that excess salt intake is associated with adverse health outcomes among individuals with normal kidney function, including hypertension, cardiovascular disease events and excess urinary albumin excretion.14-17 Randomized trials have largely corroborated these relationships,18-20 most notably the Dietary Approaches to Stop Hypertension (DASH)-Sodium Collaborative Research Group that showed that diets low in sodium significantly reduced blood pressure in study participants.21 These findings are in line with animal data showing that excess dietary sodium intake increases systemic blood pressure, induces left ventricular hypertrophy and promotes vascular damage.15, 22

The adverse effects of excess dietary sodium intake are magnified in individuals with CKD. Much like individuals with normal kidney function who are classified as “salt sensitive,”23 individuals with CKD have impaired neurohormonal mechanisms for enhancing excess sodium excretion in the urine, resulting in maladaptive increases in systemic blood pressure, renal plasma flow, and ultimately glomerular filtration pressure.24, 25 All of these factors, in turn, strongly contribute to the development of hypertension, vascular injury, and their sequelae including proteinuria and progression of renal failure, in CKD patients.2, 26 Since sodium additives make up the lion’s share of excess sodium consumption in the food supply, reducing the intake of sodium additives is paramount to improving cardiovascular and renal outcomes in CKD patients consuming a typical Westernized diet.

Regulation of Sodium Additive Use

Since only a small fraction of sodium consumed on a daily basis comes from discretionary sodium use (with the notable exception of the People’s Republic of China), sodium additives in processed foods represent the single greatest barrier to lowering sodium intake in CKD patients, particularly those who do not have the financial means to purchase fresh foods. As such, any serious public health efforts to reduce the intake of sodium in CKD patients will have to include a strategy for reducing the use of sodium additives by the food manufacturing industry.

In order to understand the key regulatory barriers to attaining this goal in the US, it is helpful to review some of the legal framework underlying food additive regulation. Much of the framework is based upon the 1958 Food Additives Amendment (FAA) to the Federal Food, Drug, and Cosmetic Act of 1938.27 In brief, this amendment defined any substances intentionally added to food by manufacturers as “food additives,” and required manufacturers to obtain approval from the Food and Drug Administration (FDA) prior to adding these substances to food (it should be noted at this juncture that the legal definition of a “food additive” as established by the FAA differs quite a bit from the more colloquial uses of the term—for this reason, food additives will be put in parentheses when referring to the legal sense of the term here on out). This approval included the requirement that substances meet the relatively steep safety standard of “reasonable certainty of no harm” under the conditions of its intended use. Importantly, however, substances that were used in ways generally recognized as safe (GRAS) or that were used in ways previously sanctioned by the FDA or the Department of Agriculture prior to the enactment of the FAA were excluded from this definition. This is critical in that most uses of salt at that time (and continuing through today) were able to be excluded from the definition of a “food additive” under these provisions, exempting salt and other sodium-based ingredients from undergoing the stringent pre-market reviews of safety required for “food additives” by the FAA.

Recognizing the importance of reviewing the GRAS status of substances over time, the FDA in 1969 designated a Select Committee on GRAS Substances (SCOGS) to review the safety profile of all current GRAS substances (including salt).10 The findings of this report raised substantive concerns about whether salt met the “reasonable certainty of no harm” safety standard, which could put it status as a GRAS substance in peril and thus, subject it to greater regulation. However, the FDA did not modify the status of salt after reviewing the results of the report, saying in essence that it did not have enough evidence to overturn its GRAS status.10 There have been further attempts to reduce salt intake over the past 32 years, including a publication of a “Policy Notice” in 1982 in which the FDA called for a reduction in salt in processed foods through public education, voluntary industry efforts, and expanded disclosure of sodium content on product labels.10 More recently, the FDA has proposed to mandate the listing of sodium content of foods in fast food establishments and restaurants in order to make it easier for consumers to identify lower sodium options.10 In addition, a 2010 Institute of Medicine report detailed a number of strategies to gradually reduce sodium content of processed foods over time.10 To date, however, these efforts have led to only marginal reductions in sodium additive intake in the US. 28

Phosphorus Additives

Dietary phosphorus consists of both “organic” sources of esterified phosphorus, such as meats, dairy products and vegetables, and “inorganic” forms of phosphorus that are commonly added to processed foods and beverages.29-31 Unlike sodium, organic or natural forms of phosphorus are plentiful in the food supply, making up the majority of phosphorus consumed on a daily basis.32 However, phosphorus-based additive use exploded during the 20th century,33 substantially augmenting total phosphorus intake in modern diets.

Phosphorus-based additives serve a number of critical functions for food manufacturing, including pH stabilization, metal cation sequestration, emulsification, leavening, hydration, and bactericidal actions, among others.33 Because of this wide diversity of applications, the use of phosphorus additives in the food manufacturing industry is immense—for example, over 40 million pounds of phosphorus additives were used annually in the US during the 1970’s by the meat industry alone,33 a figure that has likely grown over the past 40 years as demand for convenience and fast foods has increased. The magnitude of the use of phosphorus additives in the meat industry pales in comparison to that of the baking industry, which utilizes the highest quantities of phosphorus additives because of the key role that phosphorus acids play as dough leavening agents.34 In a report commissioned by the U.S. Department of Commerce in 1972, baked goods were estimated to contain nearly 10-fold higher amounts of phosphorus additives than meat products.35 Phosphorus additives, including those complexed with sodium, are also commonly used in milk and dairy products (particularly processed cheeses), seafood, and beverages. Dark colas and sodas in particular are the beverages that contain the highest amounts of phosphorus additives, principally in the form of phosphoric acid.36

Most individuals in the U.S. easily receive—and in fact usually exceed—the recommended daily allowance (RDA) of dietary phosphorus. Although the current RDA for phosphorus is 700 mg per day for adults (),37 the most recent estimates of average daily intake for US adults 20 years of age and older is ~1550 mg for males and ~1120 mg for females, due in large part to the high intake of phosphorus-rich foods in the American diet. 38 The nearly ubiquitous distribution of phosphorus additives in processed foods augments phosphorus intake even further,39 with estimates ranging from 250 to 1,000 mg of extra phosphorus per day.40-42 should be noted, however, that some of the studies from which these estimates were derived have important limitations. For example, in one highly-cited study, healthy volunteers were fed a balanced diet consisting of additive-free food for four weeks, after which they were fed a diet that looked virtually identical with the only difference being that instead of being additive-free, the foods were additive-rich.40 The measured content of phosphorus in the additive-rich diet was approximately 1,000 mg higher per day than in the additive-free diet, suggesting that additive-enhanced foods can nearly double total phosphorus intake per day. However, the meat products used as additive-rich foods in this study were manufactured using quantities of phosphorus additives nearly twice that normally used by the meat industry,33 likely exaggerating the difference in phosphorus content between the diets. Furthermore, the study was specifically designed to accentuate the differences between an additive-free and an additive-rich diet, and thus, may not be representative of more real-world scenarios in which individuals are consuming a mixture of both. Nevertheless, irrespective of the exact quantity, studies have shown that phosphorus additives can substantially increase phosphorus contents of processed foods.29, 32, 43

Importantly, despite their widespread use, phosphorus additives are typically unaccounted in the estimated phosphorus content of processed foods because food manufacturers are not required to list their quantities.31 Thus, not only do phosphorus additives increase daily phosphorus intake, they represent a largely “hidden” dietary phosphorus load in typical American diets. This is noteworthy in that phosphorus additives are absorbed with much greater efficiency in the gut (> 90%) than organic forms of phosphorus in animal or vegetable proteins (~50-60%), with potentially important consequences.31 Indeed, a study showed that foods with higher phosphorus bioavailability significantly increased serum phosphate and fibroblast growth factor 23 (FGF23) concentrations in CKD patients,44 suggesting that the high bioavailability of phosphorus additives may potentiate their adverse impact on phosphorus homeostasis in CKD.

Health Impact of Phosphorus Additive Use in CKD patients

Unlike sodium, data on the health impact of phosphorus additives are sparse in the general population, and nearly non-existent in individuals with kidney disease. Although a number of studies have examined the adverse effects of oral phosphate supplement loading in healthy volunteers,45-47 supplement loading does not take into account the effects of food processing or cooking on the biochemical properties of food additives, making it unclear how well these studies captured the physiological effects of commercial food additives in humans. The few studies that did examine the effects of additives found in commercially-processed foods were primarily done in healthy female volunteers, and in general showed that high phosphorus additive intake promoted bone loss, partly though disruptions in calcium balance.48-54 Whether high phosphorus additive intake has adverse effects on blood pressure or kidney function in healthy individuals has not been studied in detail and should be the focus of future investigation.

To date, no physiological studies have specifically examined the impact of commercially-derived phosphorus additives on bone and mineral metabolism in individuals with CKD. However, one study did examine the impact of lowering phosphorus additive intake on serum phosphate concentrations in hemodialysis patients. In this study, maintenance hemodialysis patients were taught how to read product labeling while grocery shopping in order to avoid purchasing items containing phosphorus additives and how to make better choices in choosing low-phosphorus options when eating at local fast food restaurants.55 After three months of the intervention, mean serum phosphate concentrations declined by 1.0 mg/dl in patients who received the intervention as compared to 0.4 mg/dl in control patients who did not (P for difference 0.02), suggesting a modest benefit of avoidance of phosphorus additives in hemodialysis patients. The extent to which avoidance of phosphorus additives improves phosphorus homeostasis in pre-dialysis CKD patients consuming typical Westernized diets is unclear and should be the focus of future studies.

Regulation of Phosphorus Additive Use

In recognition of the already high intake of natural forms of phosphorus in modern diets, several regulatory agencies—most notably the Joint Food and Agriculture Organization /World Health Organization Expert Committee on Food Additives (JEFCA) and the aforementioned SCOGS from the FDA—commissioned separate studies to assess the safety of phosphorus additives in processed foods. The JEFCA report, released in 1964, evaluated all available studies examining acute and chronic toxicities of high phosphorus intake.56 The main findings of the report were that phosphorus compounds commonly used as food additives at that time appeared to be safe for public consumption as long as they were not ingested in excess amounts. To aid in determining what would constitute excess amounts, the committee recommended upper limits of daily phosphorus additive intake deemed to be safe for healthy populations. Two thresholds were recommended—an “unconditional zone of acceptability” and a “conditional zone of acceptability.” The unconditional zone (30 mg/kg a day or 2,100 mg/day in a 70 kg person) represented the level of phosphorus additive use that was deemed effective for the intended purpose of the additive and could “be safely employed without further expert advice,” for example from a panel of nutrition specialists.57 The conditional zone (30 to 70 mg/kg day) represented levels that could be used safely in the community, but which should have some level of expert supervision that could be readily available for direction or advice.

Like the JEFCA report, the 1975 SCOGS report reviewed many of the same studies from the 1950’s through the early 1970’s, and came to the conclusion that phosphorus-based food additives posed little threat to consumer safety when used in quantities that “are now current or might reasonably be expected in the future.”58 As such, the FDA kept phosphorus additives among the group of GRAS substances, saying in summary, that “None of the GRAS phosphates is intrinsically harmful and their use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D and other nutrients are satisfactory.”58

While it is possible that phosphorus additives are safe for public consumption when used under these conditions, critical limitations in the literature used to derive these recommendations should prompt caution before drawing this conclusion. First, the vast majority of animal studies cited by these reports were conducted in the 1960’s and 1970’s, 20 – 30 years before the biological basis for a direct link between excess phosphorus and cardiovascular disease (ie, vascular calcification) was first reported.59 As a result, while renal and bone toxicities were carefully evaluated in these studies, the impact of excess phosphorus intake on cardiovascular health was examined in much less detail. Moreover, critical hormones involved in phosphorus homeostasis, most notably FGF23, were unknown in that era. FGF23 is a novel phosphaturic hormone that is stimulated by increased dietary phosphorus intake.60 High FGF23 concentrations have been strongly associated with cardiovascular disease, including vascular calcification, endothelial dysfunction and left ventricular hypertrophy.61-64 Since FGF23 was not discovered until the beginning of this century,65 none of these older studies examined the potential adverse effects of phosphorus additives on FGF23 secretion. Finally, very few of these studies were conducted in humans. This is a critical gap in the literature given that phosphorus toxicology research in animals rarely accounts for food processing conditions such as cooking, which may modify the biochemical properties of food additives.33 For all these reasons, the full public health implications of the high use of phosphorus additives in the food manufacturing industry remain largely unknown.

Sodium and Phosphorus-based Food Additives: Assessing the Forks in the Road

As the above discussion makes clear, addressing the high use of the additives in processed foods is critical for meaningfully reducing sodium and phosphorus intake in the general population, and CKD patients in particular, since these foods constitute such a large proportion of what most individuals consume. Although a comprehensive review of all the steps needed to arrive at this objective is beyond the scope of this review, several key points will be emphasized below.

First, any federally-mandated reductions in sodium will likely require either revoking sodium’s GRAS status (i.e., re-classifying it as a “food additive”), or altering sodium’s GRAS status to require more stringent safety standards, including limitations in the quantities that can be added to food. Both maneuvers would likely hinge on being able to convince the FDA (and other powerful political interests) that sodium-based additives violate the “reasonable certainty of no harm” safety standard, and as such, require greater monitoring and regulation. Unfortunately, this is not straight-forward, as there are a number of practical and legal hurdles that would need to be overcome to accomplish this goal (reviewed in-depth in reference 10). Nevertheless, the large and growing body of evidence showing that high sodium intake poses a real and present public health danger would form a strong foundation for sustaining such an effort. The same cannot be said about phosphorus-based food additives. Indeed, as mentioned above, data on the impact of phosphorus additives in humans is limited and/or largely extrapolated from animal studies over forty years old. Therefore, before the safety of phosphorus additives can be reasonably challenged, more studies are needed to determine the full impact of these additives on mineral metabolism and cardiovascular health.

Second, any efforts to reduce sodium additives in processed foods, whether by federal mandate or public education programs, will likely fail without addressing the strong salt preference in human populations. Indeed, the single greatest barrier to the voluntary reduction in the use of sodium additives by the food industry has been the well-founded fear that doing so would drive consumers to higher-sodium-containing products made by competitors.10 Because of this, any sustainable reductions in sodium additive use will likely require slow, step-wise, and across-the-board decreases in sodium content so that consumers gradually become accustomed to lower sodium intake, with no manufacturer gaining a competitive edge over another. Whether similar issues apply to phosphorus additives is less clear. However, given phosphorus additives’ diversity of applications in improving the taste, appearance, and shelf-life of foods, it is very possible that consumer preferences could also curtail efforts to reduce their use if these additives were lowered in too rapid or uncoordinated a manner.

Third, it will be quite important to mind the “law of unintentional consequences” in the process of implementing any of these initiatives. Indeed, it is quite ironic that previous attempts to reduce the content of sodium in food additives may have inadvertently increased the use of phosphorus additives. As postulated by one authority in the field of phosphorus additives, interest in the use of these additives in meat products spiked in the 1980’s in response to several position papers from the US National Academy of Sciences calling for reductions in the use of sodium as food additives.33 This is because phosphorus can replace many of the functions of sodium in food processing, making phosphorus additives natural alternatives to sodium, and potentially accounting for the increase in the use of these additives in the US over the past 30 years.50 As another sobering example, efforts to reduce salt added to ready-to-eat foods in the United Kingdom were linked to an outbreak of listeriosis from 2001 to 2005.10 Given sodium’s strong anti-microbial actions against pathogens such as Clostridium botulinum and Listeria monocytogenes, it will be important to understand the safety implications of reducing sodium or phosphorus in processed foods before additive-lowering programs are widely adopted.

Though formidable, none of these barriers are insurmountable. As any sustainable in-roads in reducing sodium and phosphorus intake in modern diets will require a coordinated action at all levels, it is hoped that by having a better understanding of the scope of the issue, how it uniquely impacts CKD patients, and the major impediments in resolving the situation, the nephrology community can better focus its energy and efforts in successfully working with industry, the government, and, most importantly, patients, to achieve these goals. Given that nutrition plays such a key role in CKD outcomes, these issues should be among the highest priorities in the research and clinical community.

persistent but surmountable hurdles in the management of nutrition in chronic kidney disease

Abstract

Sodium and phosphorus-based food additives are among the most commonly consumed nutrients in the world. This is because both have diverse applications in processed food manufacturing, leading to their widespread utilization by the food industry. Since most foods are naturally low in salt, sodium additives almost completely account for the excessive consumption of sodium throughout the world. Similarly, phosphorus additives represent a major and “hidden” phosphorus load in modern diets. These factors pose a major barrier to successfully lowering sodium or phosphorus intake in patients with chronic kidney disease. As such, any serious effort to reduce sodium or phosphorus consumption will require reductions in the use of these additives by the food industry. The current regulatory environment governing the use of food additives does not favor this goal, however, in large part because these additives have historically been classified as generally safe for public consumption. To overcome these barriers, coordinated efforts will be needed to demonstrate that high intakes of these additives are not safe for public consumption and as such, should be subject to greater regulatory scrutiny.

Keywords: nutrition, diet, sodium, phosphorus, chronic kidney disease

INTRODUCTION

Sodium-based food additives are among the most abundantly consumed nutrients in the world. This is because sodium salts are not only effective anti-spoilage agents, they can also serve as relatively cheap taste enhancers in a variety of foods. As a result, sodium additives are heavily utilized in processed foods, accounting for the vast majority of the excess sodium consumed throughout the world. Though discovered and utilized as a food additive later than sodium, phosphorus-based food additives have taken on a similar wide berth of uses, including as food preservatives and taste enhancers. Like sodium, phosphorus additives have become nearly indispensable in food manufacturing, substantially augmenting the phosphorus content of processed foods. The public health consequences of these trends have been well-publicized, particularly with respect to the link between excess dietary sodium intake and the increasing prevalence and severity of hypertension in both the developed and developing world. These trends have more ominous implications for millions of individuals living with chronic kidney disease (CKD), who have reduced capacity to excrete even normal dietary sodium and phosphorus loads. This review will focus on the impact of sodium- and phosphorus-based food additives on total daily intake of sodium and phosphorus in contemporary diets, the special implications this may have for individuals with chronic kidney disease, and potential strategies for reducing the consumption of sodium and phosphorus-based food additives in CKD patients.

Sodium Additives

Sodium-based food additives were introduced into the human diet somewhere between 5,000 to 10,000 years ago when they were found to retard the spoilage of poultry and meat products.1 This discovery revolutionized the capacity for early societies to preserve meat for personal consumption and/or trade purposes, markedly increasing the use of sodium in a variety of foodstuffs. The importance of this discovery is evident from historical records which show that access to salt was a cherished commodity in early societies, on par with the finest measures of wealth and social standing, and in some cases, used as a form of currency.1, 2

Historically, the primary reason to add sodium to foods was as a method for food preservation,1 based largely upon sodium’s antimicrobial properties.3 With the advent of refrigeration and other advances in food preservation, the primary motivations evolved beyond just anti-spoilage agents to enhancing the taste and palatability of foods.4 Salt (hereby referring to sodium chloride) has a number of desirable effects on foodstuffs, including improving the intensity of flavor and augmenting the overall perception of product thickness and fullness.5, 6 Consistent with this, there is remarkable congruity with respect to the excessive levels of sodium consumption across countries with very different culinary traditions,7, 8 suggesting a strong salt preference in human populations.9 Along with its preservative and taste-enhancing effects, salt is also commonly used in the fermentation, emulsification, leavening, and enhancement of foods,10 contributing to very high levels of salt usage by the food manufacturing industry.

Since most food items contain relatively low amounts of sodium naturally, the introduction of sodium additives into human food supplies effectively increased the average daily consumption of sodium from less than 400 mg per day in pre-historic times to an average of 4,000 mg per day in modern times, far above current recommendations for daily intake ().8, 11 It is estimated that only 10% of daily salt intake in Western populations comes from natural sources, whereas 75% comes from salt added to processed foods by manufacturers, and the remaining 15% from salt added during cooking or other discretionary uses.12 While Asian populations manifest similarly high levels of added sodium intake,8 there is important variability in the sources of added sodium in Eastern vs. Western countries. This was perhaps best demonstrated in the INTERMAP study, a large international cooperative study that estimated the quantity and sources of sodium intake in 4,680 individuals 40 to 59 years of age from Japan, the People’s Republic of China, the United Kingdom and the United States.13 This study showed that the majority of sodium intake in the United Kingdom and the United States came from processed breads, cereals, grains, meats, sauces and canned items with only a very small fraction (5 – 10%) coming from salt added in home cooking or at the table.8 In contrast, the majority of salt intake in Japan came from soy sauce, salted fruits and vegetables, miso soup, and fish, whereas in China, the vast majority of sodium intake (76%) came from salt added during home cooking or at the table. These differences highlight the importance of regional factors in determining the sources of sodium intake in the developed and developing world.

Table 1

United States Department of Agriculture Dietary Reference Intakes for sodium and phosphorus intake by age group

Nutrient Age RDA/AI (grams/day) TUL (grams/day)
Sodium66 0-6 months 0.12* ND
7-12 months 0.37* ND
1-3 years 1.0* 1.5
4-8 years 1.2* 1.9
9-50 years 1.5* 2.3
50-70 years 1.3* 2.3
> 70 years 1.2* 2.3
Phosphorus37 0-6 months 0.1* ND
7-12 months 0.28* ND
1-3 years 0.46 3.0
4-8 years 0.5 3.0
9-13 years 1.25 4.0
14-18 years 1.25 4.0
> 18 years 0.7 3.0
Health Impact of Sodium Additives in Individuals with Chronic Kidney Disease

Large observational studies have shown that excess salt intake is associated with adverse health outcomes among individuals with normal kidney function, including hypertension, cardiovascular disease events and excess urinary albumin excretion.14-17 Randomized trials have largely corroborated these relationships,18-20 most notably the Dietary Approaches to Stop Hypertension (DASH)-Sodium Collaborative Research Group that showed that diets low in sodium significantly reduced blood pressure in study participants.21 These findings are in line with animal data showing that excess dietary sodium intake increases systemic blood pressure, induces left ventricular hypertrophy and promotes vascular damage.15, 22

The adverse effects of excess dietary sodium intake are magnified in individuals with CKD. Much like individuals with normal kidney function who are classified as “salt sensitive,”23 individuals with CKD have impaired neurohormonal mechanisms for enhancing excess sodium excretion in the urine, resulting in maladaptive increases in systemic blood pressure, renal plasma flow, and ultimately glomerular filtration pressure.24, 25 All of these factors, in turn, strongly contribute to the development of hypertension, vascular injury, and their sequelae including proteinuria and progression of renal failure, in CKD patients.2, 26 Since sodium additives make up the lion’s share of excess sodium consumption in the food supply, reducing the intake of sodium additives is paramount to improving cardiovascular and renal outcomes in CKD patients consuming a typical Westernized diet.

Regulation of Sodium Additive Use

Since only a small fraction of sodium consumed on a daily basis comes from discretionary sodium use (with the notable exception of the People’s Republic of China), sodium additives in processed foods represent the single greatest barrier to lowering sodium intake in CKD patients, particularly those who do not have the financial means to purchase fresh foods. As such, any serious public health efforts to reduce the intake of sodium in CKD patients will have to include a strategy for reducing the use of sodium additives by the food manufacturing industry.

In order to understand the key regulatory barriers to attaining this goal in the US, it is helpful to review some of the legal framework underlying food additive regulation. Much of the framework is based upon the 1958 Food Additives Amendment (FAA) to the Federal Food, Drug, and Cosmetic Act of 1938.27 In brief, this amendment defined any substances intentionally added to food by manufacturers as “food additives,” and required manufacturers to obtain approval from the Food and Drug Administration (FDA) prior to adding these substances to food (it should be noted at this juncture that the legal definition of a “food additive” as established by the FAA differs quite a bit from the more colloquial uses of the term—for this reason, food additives will be put in parentheses when referring to the legal sense of the term here on out). This approval included the requirement that substances meet the relatively steep safety standard of “reasonable certainty of no harm” under the conditions of its intended use. Importantly, however, substances that were used in ways generally recognized as safe (GRAS) or that were used in ways previously sanctioned by the FDA or the Department of Agriculture prior to the enactment of the FAA were excluded from this definition. This is critical in that most uses of salt at that time (and continuing through today) were able to be excluded from the definition of a “food additive” under these provisions, exempting salt and other sodium-based ingredients from undergoing the stringent pre-market reviews of safety required for “food additives” by the FAA.

Recognizing the importance of reviewing the GRAS status of substances over time, the FDA in 1969 designated a Select Committee on GRAS Substances (SCOGS) to review the safety profile of all current GRAS substances (including salt).10 The findings of this report raised substantive concerns about whether salt met the “reasonable certainty of no harm” safety standard, which could put it status as a GRAS substance in peril and thus, subject it to greater regulation. However, the FDA did not modify the status of salt after reviewing the results of the report, saying in essence that it did not have enough evidence to overturn its GRAS status.10 There have been further attempts to reduce salt intake over the past 32 years, including a publication of a “Policy Notice” in 1982 in which the FDA called for a reduction in salt in processed foods through public education, voluntary industry efforts, and expanded disclosure of sodium content on product labels.10 More recently, the FDA has proposed to mandate the listing of sodium content of foods in fast food establishments and restaurants in order to make it easier for consumers to identify lower sodium options.10 In addition, a 2010 Institute of Medicine report detailed a number of strategies to gradually reduce sodium content of processed foods over time.10 To date, however, these efforts have led to only marginal reductions in sodium additive intake in the US.28

Phosphorus Additives

Dietary phosphorus consists of both “organic” sources of esterified phosphorus, such as meats, dairy products and vegetables, and “inorganic” forms of phosphorus that are commonly added to processed foods and beverages.29-31 Unlike sodium, organic or natural forms of phosphorus are plentiful in the food supply, making up the majority of phosphorus consumed on a daily basis.32 However, phosphorus-based additive use exploded during the 20th century,33 substantially augmenting total phosphorus intake in modern diets.

Phosphorus-based additives serve a number of critical functions for food manufacturing, including pH stabilization, metal cation sequestration, emulsification, leavening, hydration, and bactericidal actions, among others.33 Because of this wide diversity of applications, the use of phosphorus additives in the food manufacturing industry is immense—for example, over 40 million pounds of phosphorus additives were used annually in the US during the 1970’s by the meat industry alone,33 a figure that has likely grown over the past 40 years as demand for convenience and fast foods has increased. The magnitude of the use of phosphorus additives in the meat industry pales in comparison to that of the baking industry, which utilizes the highest quantities of phosphorus additives because of the key role that phosphorus acids play as dough leavening agents.34 In a report commissioned by the U.S. Department of Commerce in 1972, baked goods were estimated to contain nearly 10-fold higher amounts of phosphorus additives than meat products.35 Phosphorus additives, including those complexed with sodium, are also commonly used in milk and dairy products (particularly processed cheeses), seafood, and beverages. Dark colas and sodas in particular are the beverages that contain the highest amounts of phosphorus additives, principally in the form of phosphoric acid.36

Most individuals in the U.S. easily receive—and in fact usually exceed—the recommended daily allowance (RDA) of dietary phosphorus. Although the current RDA for phosphorus is 700 mg per day for adults (),37 the most recent estimates of average daily intake for US adults 20 years of age and older is ~1550 mg for males and ~1120 mg for females, due in large part to the high intake of phosphorus-rich foods in the American diet.38 The nearly ubiquitous distribution of phosphorus additives in processed foods augments phosphorus intake even further,39 with estimates ranging from 250 to 1,000 mg of extra phosphorus per day.40-42 should be noted, however, that some of the studies from which these estimates were derived have important limitations. For example, in one highly-cited study, healthy volunteers were fed a balanced diet consisting of additive-free food for four weeks, after which they were fed a diet that looked virtually identical with the only difference being that instead of being additive-free, the foods were additive-rich.40 The measured content of phosphorus in the additive-rich diet was approximately 1,000 mg higher per day than in the additive-free diet, suggesting that additive-enhanced foods can nearly double total phosphorus intake per day. However, the meat products used as additive-rich foods in this study were manufactured using quantities of phosphorus additives nearly twice that normally used by the meat industry,33 likely exaggerating the difference in phosphorus content between the diets. Furthermore, the study was specifically designed to accentuate the differences between an additive-free and an additive-rich diet, and thus, may not be representative of more real-world scenarios in which individuals are consuming a mixture of both. Nevertheless, irrespective of the exact quantity, studies have shown that phosphorus additives can substantially increase phosphorus contents of processed foods.29, 32, 43

Importantly, despite their widespread use, phosphorus additives are typically unaccounted in the estimated phosphorus content of processed foods because food manufacturers are not required to list their quantities.31 Thus, not only do phosphorus additives increase daily phosphorus intake, they represent a largely “hidden” dietary phosphorus load in typical American diets. This is noteworthy in that phosphorus additives are absorbed with much greater efficiency in the gut (> 90%) than organic forms of phosphorus in animal or vegetable proteins (~50-60%), with potentially important consequences.31 Indeed, a study showed that foods with higher phosphorus bioavailability significantly increased serum phosphate and fibroblast growth factor 23 (FGF23) concentrations in CKD patients,44 suggesting that the high bioavailability of phosphorus additives may potentiate their adverse impact on phosphorus homeostasis in CKD.

Health Impact of Phosphorus Additive Use in CKD patients

Unlike sodium, data on the health impact of phosphorus additives are sparse in the general population, and nearly non-existent in individuals with kidney disease. Although a number of studies have examined the adverse effects of oral phosphate supplement loading in healthy volunteers,45-47 supplement loading does not take into account the effects of food processing or cooking on the biochemical properties of food additives, making it unclear how well these studies captured the physiological effects of commercial food additives in humans. The few studies that did examine the effects of additives found in commercially-processed foods were primarily done in healthy female volunteers, and in general showed that high phosphorus additive intake promoted bone loss, partly though disruptions in calcium balance.48-54 Whether high phosphorus additive intake has adverse effects on blood pressure or kidney function in healthy individuals has not been studied in detail and should be the focus of future investigation.

To date, no physiological studies have specifically examined the impact of commercially-derived phosphorus additives on bone and mineral metabolism in individuals with CKD. However, one study did examine the impact of lowering phosphorus additive intake on serum phosphate concentrations in hemodialysis patients. In this study, maintenance hemodialysis patients were taught how to read product labeling while grocery shopping in order to avoid purchasing items containing phosphorus additives and how to make better choices in choosing low-phosphorus options when eating at local fast food restaurants.55 After three months of the intervention, mean serum phosphate concentrations declined by 1.0 mg/dl in patients who received the intervention as compared to 0.4 mg/dl in control patients who did not (P for difference 0.02), suggesting a modest benefit of avoidance of phosphorus additives in hemodialysis patients. The extent to which avoidance of phosphorus additives improves phosphorus homeostasis in pre-dialysis CKD patients consuming typical Westernized diets is unclear and should be the focus of future studies.

Regulation of Phosphorus Additive Use

In recognition of the already high intake of natural forms of phosphorus in modern diets, several regulatory agencies—most notably the Joint Food and Agriculture Organization /World Health Organization Expert Committee on Food Additives (JEFCA) and the aforementioned SCOGS from the FDA—commissioned separate studies to assess the safety of phosphorus additives in processed foods. The JEFCA report, released in 1964, evaluated all available studies examining acute and chronic toxicities of high phosphorus intake.56 The main findings of the report were that phosphorus compounds commonly used as food additives at that time appeared to be safe for public consumption as long as they were not ingested in excess amounts. To aid in determining what would constitute excess amounts, the committee recommended upper limits of daily phosphorus additive intake deemed to be safe for healthy populations. Two thresholds were recommended—an “unconditional zone of acceptability” and a “conditional zone of acceptability.” The unconditional zone (30 mg/kg a day or 2,100 mg/day in a 70 kg person) represented the level of phosphorus additive use that was deemed effective for the intended purpose of the additive and could “be safely employed without further expert advice,” for example from a panel of nutrition specialists.57 The conditional zone (30 to 70 mg/kg day) represented levels that could be used safely in the community, but which should have some level of expert supervision that could be readily available for direction or advice.

Like the JEFCA report, the 1975 SCOGS report reviewed many of the same studies from the 1950’s through the early 1970’s, and came to the conclusion that phosphorus-based food additives posed little threat to consumer safety when used in quantities that “are now current or might reasonably be expected in the future.”58 As such, the FDA kept phosphorus additives among the group of GRAS substances, saying in summary, that “None of the GRAS phosphates is intrinsically harmful and their use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D and other nutrients are satisfactory.”58

While it is possible that phosphorus additives are safe for public consumption when used under these conditions, critical limitations in the literature used to derive these recommendations should prompt caution before drawing this conclusion. First, the vast majority of animal studies cited by these reports were conducted in the 1960’s and 1970’s, 20 – 30 years before the biological basis for a direct link between excess phosphorus and cardiovascular disease (ie, vascular calcification) was first reported.59 As a result, while renal and bone toxicities were carefully evaluated in these studies, the impact of excess phosphorus intake on cardiovascular health was examined in much less detail. Moreover, critical hormones involved in phosphorus homeostasis, most notably FGF23, were unknown in that era. FGF23 is a novel phosphaturic hormone that is stimulated by increased dietary phosphorus intake.60 High FGF23 concentrations have been strongly associated with cardiovascular disease, including vascular calcification, endothelial dysfunction and left ventricular hypertrophy.61-64 Since FGF23 was not discovered until the beginning of this century,65 none of these older studies examined the potential adverse effects of phosphorus additives on FGF23 secretion. Finally, very few of these studies were conducted in humans. This is a critical gap in the literature given that phosphorus toxicology research in animals rarely accounts for food processing conditions such as cooking, which may modify the biochemical properties of food additives.33 For all these reasons, the full public health implications of the high use of phosphorus additives in the food manufacturing industry remain largely unknown.

Sodium and Phosphorus-based Food Additives: Assessing the Forks in the Road

As the above discussion makes clear, addressing the high use of the additives in processed foods is critical for meaningfully reducing sodium and phosphorus intake in the general population, and CKD patients in particular, since these foods constitute such a large proportion of what most individuals consume. Although a comprehensive review of all the steps needed to arrive at this objective is beyond the scope of this review, several key points will be emphasized below.

First, any federally-mandated reductions in sodium will likely require either revoking sodium’s GRAS status (i.e., re-classifying it as a “food additive”), or altering sodium’s GRAS status to require more stringent safety standards, including limitations in the quantities that can be added to food. Both maneuvers would likely hinge on being able to convince the FDA (and other powerful political interests) that sodium-based additives violate the “reasonable certainty of no harm” safety standard, and as such, require greater monitoring and regulation. Unfortunately, this is not straight-forward, as there are a number of practical and legal hurdles that would need to be overcome to accomplish this goal (reviewed in-depth in reference 10). Nevertheless, the large and growing body of evidence showing that high sodium intake poses a real and present public health danger would form a strong foundation for sustaining such an effort. The same cannot be said about phosphorus-based food additives. Indeed, as mentioned above, data on the impact of phosphorus additives in humans is limited and/or largely extrapolated from animal studies over forty years old. Therefore, before the safety of phosphorus additives can be reasonably challenged, more studies are needed to determine the full impact of these additives on mineral metabolism and cardiovascular health.

Second, any efforts to reduce sodium additives in processed foods, whether by federal mandate or public education programs, will likely fail without addressing the strong salt preference in human populations. Indeed, the single greatest barrier to the voluntary reduction in the use of sodium additives by the food industry has been the well-founded fear that doing so would drive consumers to higher-sodium-containing products made by competitors.10 Because of this, any sustainable reductions in sodium additive use will likely require slow, step-wise, and across-the-board decreases in sodium content so that consumers gradually become accustomed to lower sodium intake, with no manufacturer gaining a competitive edge over another. Whether similar issues apply to phosphorus additives is less clear. However, given phosphorus additives’ diversity of applications in improving the taste, appearance, and shelf-life of foods, it is very possible that consumer preferences could also curtail efforts to reduce their use if these additives were lowered in too rapid or uncoordinated a manner.

Third, it will be quite important to mind the “law of unintentional consequences” in the process of implementing any of these initiatives. Indeed, it is quite ironic that previous attempts to reduce the content of sodium in food additives may have inadvertently increased the use of phosphorus additives. As postulated by one authority in the field of phosphorus additives, interest in the use of these additives in meat products spiked in the 1980’s in response to several position papers from the US National Academy of Sciences calling for reductions in the use of sodium as food additives.33 This is because phosphorus can replace many of the functions of sodium in food processing, making phosphorus additives natural alternatives to sodium, and potentially accounting for the increase in the use of these additives in the US over the past 30 years.50 As another sobering example, efforts to reduce salt added to ready-to-eat foods in the United Kingdom were linked to an outbreak of listeriosis from 2001 to 2005.10 Given sodium’s strong anti-microbial actions against pathogens such as Clostridium botulinum and Listeria monocytogenes, it will be important to understand the safety implications of reducing sodium or phosphorus in processed foods before additive-lowering programs are widely adopted.

Though formidable, none of these barriers are insurmountable. As any sustainable in-roads in reducing sodium and phosphorus intake in modern diets will require a coordinated action at all levels, it is hoped that by having a better understanding of the scope of the issue, how it uniquely impacts CKD patients, and the major impediments in resolving the situation, the nephrology community can better focus its energy and efforts in successfully working with industry, the government, and, most importantly, patients, to achieve these goals. Given that nutrition plays such a key role in CKD outcomes, these issues should be among the highest priorities in the research and clinical community.

persistent but surmountable hurdles in the management of nutrition in chronic kidney disease

Abstract

Sodium and phosphorus-based food additives are among the most commonly consumed nutrients in the world. This is because both have diverse applications in processed food manufacturing, leading to their widespread utilization by the food industry. Since most foods are naturally low in salt, sodium additives almost completely account for the excessive consumption of sodium throughout the world. Similarly, phosphorus additives represent a major and “hidden” phosphorus load in modern diets. These factors pose a major barrier to successfully lowering sodium or phosphorus intake in patients with chronic kidney disease. As such, any serious effort to reduce sodium or phosphorus consumption will require reductions in the use of these additives by the food industry. The current regulatory environment governing the use of food additives does not favor this goal, however, in large part because these additives have historically been classified as generally safe for public consumption. To overcome these barriers, coordinated efforts will be needed to demonstrate that high intakes of these additives are not safe for public consumption and as such, should be subject to greater regulatory scrutiny.

Keywords: nutrition, diet, sodium, phosphorus, chronic kidney disease

INTRODUCTION

Sodium-based food additives are among the most abundantly consumed nutrients in the world. This is because sodium salts are not only effective anti-spoilage agents, they can also serve as relatively cheap taste enhancers in a variety of foods. As a result, sodium additives are heavily utilized in processed foods, accounting for the vast majority of the excess sodium consumed throughout the world. Though discovered and utilized as a food additive later than sodium, phosphorus-based food additives have taken on a similar wide berth of uses, including as food preservatives and taste enhancers. Like sodium, phosphorus additives have become nearly indispensable in food manufacturing, substantially augmenting the phosphorus content of processed foods. The public health consequences of these trends have been well-publicized, particularly with respect to the link between excess dietary sodium intake and the increasing prevalence and severity of hypertension in both the developed and developing world. These trends have more ominous implications for millions of individuals living with chronic kidney disease (CKD), who have reduced capacity to excrete even normal dietary sodium and phosphorus loads. This review will focus on the impact of sodium- and phosphorus-based food additives on total daily intake of sodium and phosphorus in contemporary diets, the special implications this may have for individuals with chronic kidney disease, and potential strategies for reducing the consumption of sodium and phosphorus-based food additives in CKD patients.

Sodium Additives

Sodium-based food additives were introduced into the human diet somewhere between 5,000 to 10,000 years ago when they were found to retard the spoilage of poultry and meat products.1 This discovery revolutionized the capacity for early societies to preserve meat for personal consumption and/or trade purposes, markedly increasing the use of sodium in a variety of foodstuffs. The importance of this discovery is evident from historical records which show that access to salt was a cherished commodity in early societies, on par with the finest measures of wealth and social standing, and in some cases, used as a form of currency.1, 2

Historically, the primary reason to add sodium to foods was as a method for food preservation,1 based largely upon sodium’s antimicrobial properties.3 With the advent of refrigeration and other advances in food preservation, the primary motivations evolved beyond just anti-spoilage agents to enhancing the taste and palatability of foods.4 Salt (hereby referring to sodium chloride) has a number of desirable effects on foodstuffs, including improving the intensity of flavor and augmenting the overall perception of product thickness and fullness.5, 6 Consistent with this, there is remarkable congruity with respect to the excessive levels of sodium consumption across countries with very different culinary traditions,7, 8 suggesting a strong salt preference in human populations.9 Along with its preservative and taste-enhancing effects, salt is also commonly used in the fermentation, emulsification, leavening, and enhancement of foods,10 contributing to very high levels of salt usage by the food manufacturing industry.

Since most food items contain relatively low amounts of sodium naturally, the introduction of sodium additives into human food supplies effectively increased the average daily consumption of sodium from less than 400 mg per day in pre-historic times to an average of 4,000 mg per day in modern times, far above current recommendations for daily intake ().8, 11 It is estimated that only 10% of daily salt intake in Western populations comes from natural sources, whereas 75% comes from salt added to processed foods by manufacturers, and the remaining 15% from salt added during cooking or other discretionary uses.12 While Asian populations manifest similarly high levels of added sodium intake,8 there is important variability in the sources of added sodium in Eastern vs. Western countries. This was perhaps best demonstrated in the INTERMAP study, a large international cooperative study that estimated the quantity and sources of sodium intake in 4,680 individuals 40 to 59 years of age from Japan, the People’s Republic of China, the United Kingdom and the United States.13 This study showed that the majority of sodium intake in the United Kingdom and the United States came from processed breads, cereals, grains, meats, sauces and canned items with only a very small fraction (5 – 10%) coming from salt added in home cooking or at the table.8 In contrast, the majority of salt intake in Japan came from soy sauce, salted fruits and vegetables, miso soup, and fish, whereas in China, the vast majority of sodium intake (76%) came from salt added during home cooking or at the table. These differences highlight the importance of regional factors in determining the sources of sodium intake in the developed and developing world.

Table 1

United States Department of Agriculture Dietary Reference Intakes for sodium and phosphorus intake by age group

Nutrient Age RDA/AI (grams/day) TUL (grams/day)
Sodium66 0-6 months 0.12* ND
7-12 months 0.37* ND
1-3 years 1.0* 1.5
4-8 years 1.2* 1.9
9-50 years 1.5* 2.3
50-70 years 1.3* 2.3
> 70 years 1.2* 2.3
Phosphorus37 0-6 months 0.1* ND
7-12 months 0.28* ND
1-3 years 0.46 3.0
4-8 years 0.5 3.0
9-13 years 1.25 4.0
14-18 years 1.25 4.0
> 18 years 0.7 3.0
Health Impact of Sodium Additives in Individuals with Chronic Kidney Disease

Large observational studies have shown that excess salt intake is associated with adverse health outcomes among individuals with normal kidney function, including hypertension, cardiovascular disease events and excess urinary albumin excretion.14-17 Randomized trials have largely corroborated these relationships,18-20 most notably the Dietary Approaches to Stop Hypertension (DASH)-Sodium Collaborative Research Group that showed that diets low in sodium significantly reduced blood pressure in study participants.21 These findings are in line with animal data showing that excess dietary sodium intake increases systemic blood pressure, induces left ventricular hypertrophy and promotes vascular damage.15, 22

The adverse effects of excess dietary sodium intake are magnified in individuals with CKD. Much like individuals with normal kidney function who are classified as “salt sensitive,”23 individuals with CKD have impaired neurohormonal mechanisms for enhancing excess sodium excretion in the urine, resulting in maladaptive increases in systemic blood pressure, renal plasma flow, and ultimately glomerular filtration pressure.24, 25 All of these factors, in turn, strongly contribute to the development of hypertension, vascular injury, and their sequelae including proteinuria and progression of renal failure, in CKD patients.2, 26 Since sodium additives make up the lion’s share of excess sodium consumption in the food supply, reducing the intake of sodium additives is paramount to improving cardiovascular and renal outcomes in CKD patients consuming a typical Westernized diet.

Regulation of Sodium Additive Use

Since only a small fraction of sodium consumed on a daily basis comes from discretionary sodium use (with the notable exception of the People’s Republic of China), sodium additives in processed foods represent the single greatest barrier to lowering sodium intake in CKD patients, particularly those who do not have the financial means to purchase fresh foods. As such, any serious public health efforts to reduce the intake of sodium in CKD patients will have to include a strategy for reducing the use of sodium additives by the food manufacturing industry.

In order to understand the key regulatory barriers to attaining this goal in the US, it is helpful to review some of the legal framework underlying food additive regulation. Much of the framework is based upon the 1958 Food Additives Amendment (FAA) to the Federal Food, Drug, and Cosmetic Act of 1938.27 In brief, this amendment defined any substances intentionally added to food by manufacturers as “food additives,” and required manufacturers to obtain approval from the Food and Drug Administration (FDA) prior to adding these substances to food (it should be noted at this juncture that the legal definition of a “food additive” as established by the FAA differs quite a bit from the more colloquial uses of the term—for this reason, food additives will be put in parentheses when referring to the legal sense of the term here on out). This approval included the requirement that substances meet the relatively steep safety standard of “reasonable certainty of no harm” under the conditions of its intended use. Importantly, however, substances that were used in ways generally recognized as safe (GRAS) or that were used in ways previously sanctioned by the FDA or the Department of Agriculture prior to the enactment of the FAA were excluded from this definition. This is critical in that most uses of salt at that time (and continuing through today) were able to be excluded from the definition of a “food additive” under these provisions, exempting salt and other sodium-based ingredients from undergoing the stringent pre-market reviews of safety required for “food additives” by the FAA.

Recognizing the importance of reviewing the GRAS status of substances over time, the FDA in 1969 designated a Select Committee on GRAS Substances (SCOGS) to review the safety profile of all current GRAS substances (including salt).10 The findings of this report raised substantive concerns about whether salt met the “reasonable certainty of no harm” safety standard, which could put it status as a GRAS substance in peril and thus, subject it to greater regulation. However, the FDA did not modify the status of salt after reviewing the results of the report, saying in essence that it did not have enough evidence to overturn its GRAS status.10 There have been further attempts to reduce salt intake over the past 32 years, including a publication of a “Policy Notice” in 1982 in which the FDA called for a reduction in salt in processed foods through public education, voluntary industry efforts, and expanded disclosure of sodium content on product labels.10 More recently, the FDA has proposed to mandate the listing of sodium content of foods in fast food establishments and restaurants in order to make it easier for consumers to identify lower sodium options.10 In addition, a 2010 Institute of Medicine report detailed a number of strategies to gradually reduce sodium content of processed foods over time.10 To date, however, these efforts have led to only marginal reductions in sodium additive intake in the US.28

Phosphorus Additives

Dietary phosphorus consists of both “organic” sources of esterified phosphorus, such as meats, dairy products and vegetables, and “inorganic” forms of phosphorus that are commonly added to processed foods and beverages.29-31 Unlike sodium, organic or natural forms of phosphorus are plentiful in the food supply, making up the majority of phosphorus consumed on a daily basis.32 However, phosphorus-based additive use exploded during the 20th century,33 substantially augmenting total phosphorus intake in modern diets.

Phosphorus-based additives serve a number of critical functions for food manufacturing, including pH stabilization, metal cation sequestration, emulsification, leavening, hydration, and bactericidal actions, among others.33 Because of this wide diversity of applications, the use of phosphorus additives in the food manufacturing industry is immense—for example, over 40 million pounds of phosphorus additives were used annually in the US during the 1970’s by the meat industry alone,33 a figure that has likely grown over the past 40 years as demand for convenience and fast foods has increased. The magnitude of the use of phosphorus additives in the meat industry pales in comparison to that of the baking industry, which utilizes the highest quantities of phosphorus additives because of the key role that phosphorus acids play as dough leavening agents.34 In a report commissioned by the U.S. Department of Commerce in 1972, baked goods were estimated to contain nearly 10-fold higher amounts of phosphorus additives than meat products.35 Phosphorus additives, including those complexed with sodium, are also commonly used in milk and dairy products (particularly processed cheeses), seafood, and beverages. Dark colas and sodas in particular are the beverages that contain the highest amounts of phosphorus additives, principally in the form of phosphoric acid.36

Most individuals in the U.S. easily receive—and in fact usually exceed—the recommended daily allowance (RDA) of dietary phosphorus. Although the current RDA for phosphorus is 700 mg per day for adults (),37 the most recent estimates of average daily intake for US adults 20 years of age and older is ~1550 mg for males and ~1120 mg for females, due in large part to the high intake of phosphorus-rich foods in the American diet.38 The nearly ubiquitous distribution of phosphorus additives in processed foods augments phosphorus intake even further,39 with estimates ranging from 250 to 1,000 mg of extra phosphorus per day.40-42 should be noted, however, that some of the studies from which these estimates were derived have important limitations. For example, in one highly-cited study, healthy volunteers were fed a balanced diet consisting of additive-free food for four weeks, after which they were fed a diet that looked virtually identical with the only difference being that instead of being additive-free, the foods were additive-rich.40 The measured content of phosphorus in the additive-rich diet was approximately 1,000 mg higher per day than in the additive-free diet, suggesting that additive-enhanced foods can nearly double total phosphorus intake per day. However, the meat products used as additive-rich foods in this study were manufactured using quantities of phosphorus additives nearly twice that normally used by the meat industry,33 likely exaggerating the difference in phosphorus content between the diets. Furthermore, the study was specifically designed to accentuate the differences between an additive-free and an additive-rich diet, and thus, may not be representative of more real-world scenarios in which individuals are consuming a mixture of both. Nevertheless, irrespective of the exact quantity, studies have shown that phosphorus additives can substantially increase phosphorus contents of processed foods.29, 32, 43

Importantly, despite their widespread use, phosphorus additives are typically unaccounted in the estimated phosphorus content of processed foods because food manufacturers are not required to list their quantities.31 Thus, not only do phosphorus additives increase daily phosphorus intake, they represent a largely “hidden” dietary phosphorus load in typical American diets. This is noteworthy in that phosphorus additives are absorbed with much greater efficiency in the gut (> 90%) than organic forms of phosphorus in animal or vegetable proteins (~50-60%), with potentially important consequences.31 Indeed, a study showed that foods with higher phosphorus bioavailability significantly increased serum phosphate and fibroblast growth factor 23 (FGF23) concentrations in CKD patients,44 suggesting that the high bioavailability of phosphorus additives may potentiate their adverse impact on phosphorus homeostasis in CKD.

Health Impact of Phosphorus Additive Use in CKD patients

Unlike sodium, data on the health impact of phosphorus additives are sparse in the general population, and nearly non-existent in individuals with kidney disease. Although a number of studies have examined the adverse effects of oral phosphate supplement loading in healthy volunteers,45-47 supplement loading does not take into account the effects of food processing or cooking on the biochemical properties of food additives, making it unclear how well these studies captured the physiological effects of commercial food additives in humans. The few studies that did examine the effects of additives found in commercially-processed foods were primarily done in healthy female volunteers, and in general showed that high phosphorus additive intake promoted bone loss, partly though disruptions in calcium balance.48-54 Whether high phosphorus additive intake has adverse effects on blood pressure or kidney function in healthy individuals has not been studied in detail and should be the focus of future investigation.

To date, no physiological studies have specifically examined the impact of commercially-derived phosphorus additives on bone and mineral metabolism in individuals with CKD. However, one study did examine the impact of lowering phosphorus additive intake on serum phosphate concentrations in hemodialysis patients. In this study, maintenance hemodialysis patients were taught how to read product labeling while grocery shopping in order to avoid purchasing items containing phosphorus additives and how to make better choices in choosing low-phosphorus options when eating at local fast food restaurants.55 After three months of the intervention, mean serum phosphate concentrations declined by 1.0 mg/dl in patients who received the intervention as compared to 0.4 mg/dl in control patients who did not (P for difference 0.02), suggesting a modest benefit of avoidance of phosphorus additives in hemodialysis patients. The extent to which avoidance of phosphorus additives improves phosphorus homeostasis in pre-dialysis CKD patients consuming typical Westernized diets is unclear and should be the focus of future studies.

Regulation of Phosphorus Additive Use

In recognition of the already high intake of natural forms of phosphorus in modern diets, several regulatory agencies—most notably the Joint Food and Agriculture Organization /World Health Organization Expert Committee on Food Additives (JEFCA) and the aforementioned SCOGS from the FDA—commissioned separate studies to assess the safety of phosphorus additives in processed foods. The JEFCA report, released in 1964, evaluated all available studies examining acute and chronic toxicities of high phosphorus intake.56 The main findings of the report were that phosphorus compounds commonly used as food additives at that time appeared to be safe for public consumption as long as they were not ingested in excess amounts. To aid in determining what would constitute excess amounts, the committee recommended upper limits of daily phosphorus additive intake deemed to be safe for healthy populations. Two thresholds were recommended—an “unconditional zone of acceptability” and a “conditional zone of acceptability.” The unconditional zone (30 mg/kg a day or 2,100 mg/day in a 70 kg person) represented the level of phosphorus additive use that was deemed effective for the intended purpose of the additive and could “be safely employed without further expert advice,” for example from a panel of nutrition specialists.57 The conditional zone (30 to 70 mg/kg day) represented levels that could be used safely in the community, but which should have some level of expert supervision that could be readily available for direction or advice.

Like the JEFCA report, the 1975 SCOGS report reviewed many of the same studies from the 1950’s through the early 1970’s, and came to the conclusion that phosphorus-based food additives posed little threat to consumer safety when used in quantities that “are now current or might reasonably be expected in the future.”58 As such, the FDA kept phosphorus additives among the group of GRAS substances, saying in summary, that “None of the GRAS phosphates is intrinsically harmful and their use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D and other nutrients are satisfactory.”58

While it is possible that phosphorus additives are safe for public consumption when used under these conditions, critical limitations in the literature used to derive these recommendations should prompt caution before drawing this conclusion. First, the vast majority of animal studies cited by these reports were conducted in the 1960’s and 1970’s, 20 – 30 years before the biological basis for a direct link between excess phosphorus and cardiovascular disease (ie, vascular calcification) was first reported.59 As a result, while renal and bone toxicities were carefully evaluated in these studies, the impact of excess phosphorus intake on cardiovascular health was examined in much less detail. Moreover, critical hormones involved in phosphorus homeostasis, most notably FGF23, were unknown in that era. FGF23 is a novel phosphaturic hormone that is stimulated by increased dietary phosphorus intake.60 High FGF23 concentrations have been strongly associated with cardiovascular disease, including vascular calcification, endothelial dysfunction and left ventricular hypertrophy.61-64 Since FGF23 was not discovered until the beginning of this century,65 none of these older studies examined the potential adverse effects of phosphorus additives on FGF23 secretion. Finally, very few of these studies were conducted in humans. This is a critical gap in the literature given that phosphorus toxicology research in animals rarely accounts for food processing conditions such as cooking, which may modify the biochemical properties of food additives.33 For all these reasons, the full public health implications of the high use of phosphorus additives in the food manufacturing industry remain largely unknown.

Sodium and Phosphorus-based Food Additives: Assessing the Forks in the Road

As the above discussion makes clear, addressing the high use of the additives in processed foods is critical for meaningfully reducing sodium and phosphorus intake in the general population, and CKD patients in particular, since these foods constitute such a large proportion of what most individuals consume. Although a comprehensive review of all the steps needed to arrive at this objective is beyond the scope of this review, several key points will be emphasized below.

First, any federally-mandated reductions in sodium will likely require either revoking sodium’s GRAS status (i.e., re-classifying it as a “food additive”), or altering sodium’s GRAS status to require more stringent safety standards, including limitations in the quantities that can be added to food. Both maneuvers would likely hinge on being able to convince the FDA (and other powerful political interests) that sodium-based additives violate the “reasonable certainty of no harm” safety standard, and as such, require greater monitoring and regulation. Unfortunately, this is not straight-forward, as there are a number of practical and legal hurdles that would need to be overcome to accomplish this goal (reviewed in-depth in reference 10). Nevertheless, the large and growing body of evidence showing that high sodium intake poses a real and present public health danger would form a strong foundation for sustaining such an effort. The same cannot be said about phosphorus-based food additives. Indeed, as mentioned above, data on the impact of phosphorus additives in humans is limited and/or largely extrapolated from animal studies over forty years old. Therefore, before the safety of phosphorus additives can be reasonably challenged, more studies are needed to determine the full impact of these additives on mineral metabolism and cardiovascular health.

Second, any efforts to reduce sodium additives in processed foods, whether by federal mandate or public education programs, will likely fail without addressing the strong salt preference in human populations. Indeed, the single greatest barrier to the voluntary reduction in the use of sodium additives by the food industry has been the well-founded fear that doing so would drive consumers to higher-sodium-containing products made by competitors.10 Because of this, any sustainable reductions in sodium additive use will likely require slow, step-wise, and across-the-board decreases in sodium content so that consumers gradually become accustomed to lower sodium intake, with no manufacturer gaining a competitive edge over another. Whether similar issues apply to phosphorus additives is less clear. However, given phosphorus additives’ diversity of applications in improving the taste, appearance, and shelf-life of foods, it is very possible that consumer preferences could also curtail efforts to reduce their use if these additives were lowered in too rapid or uncoordinated a manner.

Third, it will be quite important to mind the “law of unintentional consequences” in the process of implementing any of these initiatives. Indeed, it is quite ironic that previous attempts to reduce the content of sodium in food additives may have inadvertently increased the use of phosphorus additives. As postulated by one authority in the field of phosphorus additives, interest in the use of these additives in meat products spiked in the 1980’s in response to several position papers from the US National Academy of Sciences calling for reductions in the use of sodium as food additives.33 This is because phosphorus can replace many of the functions of sodium in food processing, making phosphorus additives natural alternatives to sodium, and potentially accounting for the increase in the use of these additives in the US over the past 30 years.50 As another sobering example, efforts to reduce salt added to ready-to-eat foods in the United Kingdom were linked to an outbreak of listeriosis from 2001 to 2005.10 Given sodium’s strong anti-microbial actions against pathogens such as Clostridium botulinum and Listeria monocytogenes, it will be important to understand the safety implications of reducing sodium or phosphorus in processed foods before additive-lowering programs are widely adopted.

Though formidable, none of these barriers are insurmountable. As any sustainable in-roads in reducing sodium and phosphorus intake in modern diets will require a coordinated action at all levels, it is hoped that by having a better understanding of the scope of the issue, how it uniquely impacts CKD patients, and the major impediments in resolving the situation, the nephrology community can better focus its energy and efforts in successfully working with industry, the government, and, most importantly, patients, to achieve these goals. Given that nutrition plays such a key role in CKD outcomes, these issues should be among the highest priorities in the research and clinical community.

6 Things to Know About Phosphorus in Your Diet

What is phosphorus?

Phosphorus is a mineral found in your bones. Along with calcium, phosphorus is needed to build strong healthy bones, as well as, keeping other parts of your body healthy.

Why is phosphorus important to you?

Normal working kidneys can remove extra phosphorus in your blood. When you have chronic kidney disease (CKD), your kidneys cannot remove phosphorus very well. High phosphorus levels can cause damage to your body. Extra phosphorus causes body changes that pull calcium out of your bones, making them weak. High phosphorus and calcium levels also lead to dangerous calcium deposits in blood vessels, lungs, eyes, and heart. Over time this can lead to increased risk of heart attack, stroke or death. Phosphorus and calcium control are very important for your overall health.

What is a safe blood level of phosphorus?

A normal phosphorus level is 2.5 to 4.5 mg/dL. Ask your kidney doctor or dietitian what your last phosphorus level was and write it down to help keep track of it.

Will dialysis help with phosphorus control?

Yes. Dialysis can remove some phosphorus from your blood. It is important for you to understand how to limit build-up of phosphorus between your dialysis treatments.

How can I control my phosphorus level?

You can keep you phosphorus level normal by understanding your diet and medications for phosphorus control. Phosphorus can be found in foods (organic phosphorus) and is naturally found in protein-rich foods such as meats, poultry, fish, nuts, beans and dairy products. Phosphorus found in animal foods is absorbed more easily than phosphorus found in plant foods.

Phosphorus that has been added to food in the form of an additive or preservative (inorganic phosphorus) is found in foods such as fast foods, ready to eat foods, canned and bottled drinks, enhanced meats, and most processed foods. Phosphorus from food additives is completely absorbed. Avoiding phosphorus additives can lower your intake of phosphorus. Phosphorus additives are found on the list of ingredients on the nutrition facts label. Look for “PHOS” to find phosphorus additives in the food.

Phosphorus additives found in foods include:

  • Dicalcium phosphate
  • Disodium phosphate
  • Monosodium phosphate
  • Phosphoric acid
  • Sodium hexameta-phosphate
  • Trisodium phosphate
  • Sodium tripolyphosphate
  • Tetrasodium pyrophosphate

Your kidney dietitian and doctor will help you with this. Below is a list of foods high in phosphorous and lower phosphorus alternatives to enjoy:

HIGH PHOSPHORUS FOOD TO LIMIT OR AVOID

 Beverages

beer/ale

chocolate drinks

 

cocoa

dark colas

 

drinks made with milk
canned iced teas

pepper type soda (Dr Pepper)

 

bottled beverages with phosphate additives

Lower phosphorus alternatives to enjoy: water, coffee, tea, rice milk (unenriched), apple juice, cranberry juice, grape juice, lemonade, ginger ale, lemon lime soda, orange soda, root beer

 

 

Dairy Products

 

cheese

 

 

custard

ice cream

 

milk

pudding

 

cream soups

Lower phosphorus alternatives to enjoy: rice milk, almond milk, cottage cheese, vegan cheese, sherbet, popsicles

yogurt (Greek type acceptable)

 

Protein

 

oysters

 

sardines

 

beef liver

chicken liver

 

fish roe

organ meats

 

Lower phosphorus alternatives to enjoy: chicken, turkey, fish, beef, veal, eggs, lamb, pork

 

Other foods

 

chocolate candy
caramels
oat bran muffin

Lower phosphorus alternatives to enjoy: apples, berries, grapes, carrot sticks, cucumber, rice cakes, unsalted pretzels, unsalted popcorn, unsalted crackers, pound cake, sugar cookies

 

most processed/prepared foods/deli meats/hot dogs/bacon/sausage
pizza
brewer’s yeast
chocolate
caramel candies

Looking for nutrition guidance? Contact a CKD dietitian in your area.

What medications are for phosphorus control?

Your kidney doctor may order a medicine called a phosphate binder for you to take with meals and snacks. This medicine will help control the amount of phosphorus your body absorbs from the foods you eat.

There are many different kinds of phosphate binders. Pills, chewable tablets, powders, and liquids are available. Some types also contain calcium, while others do not. You should only take the phosphate binder that is ordered by your doctor or dietitian.

Read more about Phosphorus and Your CKD Diet.

Phosphorus Infographic

Acknowledgment: Reviewed by the Council on Renal Nutrition (04/2019)

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Routine Monitoring of Sodium and Phosphorus Removal in Peritoneal Dialysis (PD) Patients Treated with Continuous Ambulatory PD (CAPD), Automated PD (APD) or Combined CAPD+APD – FullText – Kidney and Blood Pressure Research 2017, Vol. 42, No. 2

Abstract

Background: Adequate removal of sodium (Na) and phosphorus (P) is of paramount importance for patients with dialysis-dependent kidney disease can easily quantified in peritoneal dialysis (PD) patients. Some studies suggest that automated PD (APD) results in lower Na and P removal. Methods: In this study we retrospectively analysed our data on Na and P removal in PD patients after implementation of a routine monitoring in 2011. Patients were stratified in those treated with continuous ambulatory PD (CAPD, n=24), automated PD (APD, n=23) and APD with one bag change (CAPD+APD, n=10). Until 2015 we collected time-varying data on Na and P removal from each patient (median 5 [interquartile range 4-8] values). Results: Peritoneal Na and P removal (mmol per 24h ± standard deviation) was 102 ± 48 and 8 ± 2 in the CAPD, 90 ± 46 and 9 ± 3 in the APD and 126 ± 39 and 13 ± 2 in the CAPD+APD group (ANOVA P=0.141 and <0.001). Taking renal excretion into account total Na and P removal (mmol per 24h) was 221 ± 65 and 16 ± 5 in the CAPD, 189 ± 58 and 17 ± 6 in the APD and 183 ± 38 and 16 ± 6 in the CAPD+APD group (P=0.107 and 0.764). Over time, peritoneal removal of Na but not that of P increased in all groups. In patients with modifications of PD treatment, Na but not P removal was significantly increased over-time. Conclusions: Overall Na and P removal were similar with different PD modalities. Individualized adjustments of PD prescription including icodextrin use or higher glucose concentration can improve Na removal while P removal is mainly determined by the dialysate volume.

© 2017 The Author(s). Published by S. Karger AG, Basel


Introduction

Chronic kidney disease (CKD) leads to disturbance of whole-body sodium (Na) and phosphorus (P) balance and typically results in Na and P retention in advanced renal disease, particularly in those with dialysis-dependent end-stage renal disease (ESRD). Na and P retention are key elements in the pathogenesis of cardiac impairment and secondary hyperparathyroidism, both important predictors of mortality in ESRD patients [1-4]. Hence, adequate Na and P removal is of paramount importance for dialysis-dependent ESRD patients [5]. In contrast to hemodialysis patients, removal of Na and P can easily be quantified in peritoneal dialysis (PD) patients. A recent study suggested that PD results in higher P retention due to reduced clearance compared to HD [6]. This could be particularly true for patients treated with automated PD (APD) that has been reported to result in lower Na and P removal [7-9]. For Na, lower removal during APD can be explained by sodium sieving during the first hour of the dwell time due to transcellular water transport by aquaporins [10, 11]. Net Na mass transfer takes place thereafter through small pores driven by chemical gradient and solvent drag. For P, transport across the peritoneum also involves small pores and is hindered by the intracellular distribution of P and the large radius of the hydrated phosphate ions [12]. Hence, adequate peritoneal Na and P removal is expected to be higher with an increasing dwell time and a higher P transporter status [9, 13].

Given these caveats, Na and P removal can still be influenced by the PD prescription such as adapting dialysate volume, glucose concentration, usage of icodextrin or number of exchanges [14]. As residual renal function deteriorates adequacy of Na and P removal by PD becomes even more important. Measuring Na and P removal PD helps to assess the efficacy of the current regimen and to adapt the PD prescription when there is evidence of Na and P retention, particularly in APD patients. It furthers helps to illustrate how much of Na and P the patient can orally ingest to maintain balance. For these reasons, we have implemented a routine monitoring of Na and P removal in our center that is measured in addition to measurement of Kt/V and weekly creatinine clearance. Here we report on the results of this monitoring during a 4-year time span (2011-2015) with emphasis on the PD modality and time trends.

Materials and Methods

Study design and subjects

All incident and prevalent PD patients treated in our department since implementation of routine monitoring of Na and P removal in October 2011 were enrolled in the study. This routine monitoring was done at the outpatient visits of each patient every 3 months in addition to measurement of Kt/V and weekly creatinine clearance from the effluent and urine that had been collected on the previous day. Na and P removal were calculated from the measured Na (using ion-selective electrodes) and P concentrations and the effluent and urine volumes. For Na, values had to be corrected for the Na content of the dialysate volume. GFR was taken as the average of creatinine and urea clearance that were calculated from the 24 h urine. Measurements of the urine and effluent Na and P concentration were done on the same day of the outpatient visit and then transferred to the dialysis software Nephro 7 (Medvision, Bad Soest, Germany) that was programmed to compute the peritoneal and renal Na and P removal. Data for this retrospective study were extracted from the electronic file until September 1st 2015.

51 patients were stratified in those treated with CAPD, APD and combined CAPD+APD. 6 patients who changed PD modality were analysed per modality resulting in group sizes of 24 patients in the CAPD, 23 patients in the APD and 10 patients in the CAPD+APD group. Patients were treated with glucose 1.36% and/or 2.27 and/or 3.86% (only double-chamber bags), amino acids 1.1% and icodextrin 7.5% as clinically needed. CAPD was performed with 3 to 4 manual bag changes per day. APD was done with a cycler (Baxter, Deerfield, Illinois, USA) over 7.5-9 hours with 4-6 cycles, 75-85 % tidal volume and a last fill of 1.5-2 L during daytime. CAPD+APD was similarly performed as usual APD except for an additional 3-5 hours daytime fill with 2 L at 6 pm until begin of overnight APD. The decision about treatment modality CAPD vs. APD primarily related to the patient’s preference and secondly to transporter status. High transporters with low ultrafiltration were treated with APD. CAPD+APD was commenced when residual renal function strongly declined and adequacy goals were not achieved. Volume status was measured with the bioimpedance spectroscopy (BCM monitor, Fresenius Medical Care Homburg, Germany). Blood pressure data were derived from self-measurements with a uniform oscillometric device provided by Baxter (Deerfield, Illinois, USA). The study was approved the local ethics committee.

Statistical analysis

Each studied parameter was arithmetically averaged per patient over the whole study period and this average value was used in final analyses. The median number of replicates per patient was 5 (interquartile range 4-8) values during a median study period of 1.4 (1.1;2.6) years per patient. Differences between the groups were analysed with one-way analysis of variance (ANOVA) with Tukey-Kramer post-test. To account for differences in patient characteristics (table 1), groups were additionally compared with oneway analysis of covariance (ANCOVA) with adjustments made for time on PD, glucose concentration, usage of icodextrin (yes or no), dialysate volume and residual GFR. To analyse the time trend of the parameters, all single replicate values of a patient were entered by treatment group into a mixed model with time as fixed effects and patient identifier as random effects. To test group-specific differences in the time trend, the mixed model was repeated with group as an interaction term. Variables entering multivariable linear regression were selected from stepwise approach (enter when p<0.2, remove when p>0.21). Statistical analyses were done with MedCalc Statistical Software version 16.4.2 (MedCalc Software bvba, Ostend, Belgium) and JMP 11 (SAS Institute Inc., Cary, NC, USA).

Table 1.

Patient characteristics. Arithmetic means ± SD. P derived from ANOVA

Results

Table 1 shows the characteristics of the groups that significantly differed with respect to time on PD, average glucose concentration, usage of icodextrin, dialysate volume and residual GFR. Patients with CAPD+APD were longer on PD, had lower residual GFR, highest dialysate volume and glucose concentration as well as icodextrin usage. Transporter status was not different across the groups. Total Kt/V and weekly creatinine clearance were highest among CAPD patients followed by APD patients. CAPD+APD patients had the lowest clearance values, particularly weekly creatinine clearance (table 1).

As shown in Fig. 1A, CAPD+APD patients had the highest ultrafiltration and inversely the lowest urine volume. CAPD patients had the lowest ultrafiltration, yet the highest urine volume resulting in the highest total fluid excretion. Peritoneal, renal and total Na removal is shown Fig. 1B. Peritoneal Na removal was slightly lower in the APD group reaching statistical significance after adjusting for group differences with ANCOVA. In the CAPD+APD group, peritoneal Na removal was highest while renal Na excretion was the lowest. Total Na removal was similar across all groups with a tendency to highest values in the CAPD group. Peritoneal, renal and total P removal is shown Fig. 1C. Peritoneal P removal was significantly higher and renal P excretion lower in the CAPD+APD group compared to the other groups. Total P excretion was similar across the groups.

Fig. 1.

Removal of fluid (A) by ultrafiltration and residual diuresis as well as peritoneal and renal removal of Na (B) and P (C). Total removal is derived from the sum of peritoneal and renal excretion. Arithmetic means with SD.

Table 2 shows the time- and group-dependent changes in peritoneal and renal clearance as analysed with a mixed linear regression model. GFR was lost in the CAPD and APD groups with a similar rate, in the CAPD+APD the value was somewhat lower which may be explained with a very low baseline GFR. Similarly, urine volume fell in all groups by 236-266 ml per year. Inversely, dialysate volume increased in all groups, particularly in the APD and CAPD+APD group. As a result, ultrafiltration also increased with time which was, however, less pronounced in the APD group. While renal Na removal decreased, peritoneal Na removal increased with time and a tendency towards group-specific differences. Interestingly, peritoneal P removal remained stable throughout the study period, while renal P excretion decreased in all groups with time.

Table 2.

Time dependence of studied parameters, Results of a mixed model with time as independent variable and group as an interaction term. Slope values of individual patients were averaged to give a quantitative estimate of the change with time

During the study period PD treatment was modified in 6 (12%) patients who changed PD modality, mainly from CAPD to APD, and in 33 (58%) patients whose PD treatment was changed (table 3). The median number of treatment changes were on average two per patient and similar across the groups (table 3, p=0.22). During the first regimen, patients with and without treatment changes had a similar glucose concentration (1.74 [1.36; 1.97] vs. 1.82 % [1.59; 2.10], p=0.31) and dialysate volume (7.76 [4.5; 10.0] vs. 7.91 L [5.0; 10.0], p=0.74). In patients with treatment changes, glucose concentration and dialysate volume were significantly increased to 2.04 % ([1.36; 2.27], p=0.008) and 8.7 L ([4.5; 10.0], p=0.03). To analyse if the treatment changes resulted in increased solute removal we reanalysed the time-dependent data after stratification of patients with or without treatment changes. As shown in table 4, patients with treatment changes had significantly higher time-dependent changes in dialysate volume, ultrafiltration and peritoneal Na but not P removal compared to patients without treatment changes (table 4). Time-dependent changes of peritoneal Kt/V and creatinine clearance were not significantly different between the groups, although they tended to increase in the patients with treatment changes.

Table 3.

Course of PD treatment during study period

Table 4.

Time dependence of peritoneal solute elimination according to treatment changes. Results of a mixed model with time as independent variable stratified according to treatment changes (yes/no). Treatment modality was not entered into the model. Slope values of individual patients were averaged to give a quantitative estimate of the change with time

We also assessed the surrogates for Na and P retention such as increased blood pressure, overhydration, hyperphosphatemia and secondary hyperparathyroidism. As shown in Fig. 2A, systolic and diastolic blood pressure was not different between groups although patients with APD and CAPD+APD tended to have higher systolic and diastolic blood pressure. Overhydration as surrogate of Na retention was common in all groups and was highest in the CAPD group (Fig. 2B). Inversion of extracellular to intracellular water (E/I) was uniformly found across all groups. The number of antihypertensives including diuretics was 3–5 drug classes per patient with a great variability and no significant difference (Fig. 2C).

Fig. 2.

Surrogates for Na retention and use of antihypertensive drugs, A Systolic and diastolic blood pressure, B Overhydration and ratio of extra- to intracellular water (E/I) from bioimpedance spectroscopy, C Number of classes of antihypertensive drug including diuretics (torasemid and xipamide counted separately). Arithmetic means with SD.

Patients in the CAPD+APD group had the highest plasma phosphorus concentration (Fig. 3A) while plasma calcium values were very similar in all groups (2.2-2.3 mM, P=0.108; data not shown). Parathyroid hormone concentration was similar across all groups (Fig. 3A). CAPD+APD patients took the highest number of pills to bind phosphorus (Fig. 3B). However, the great variability precluded significant differences. Native and active vitamin D usage was identical in all groups (10 000 IE native vitamin D per week and 0.23 µg per day, P=0.728 and 0.667).

Fig. 3.

Surrogates for P retention and use of phosphorus binders, Hyperphosphatemia (A), secondary hyperparathyroidism (B) and number of pills to bind phosphorus (C) including lanthan, calcium-containing, sevelamer and aluminium. Arithmetic means with SD.

Table 5 shows the results of a multivariate linear regression analysis to identify independent predictors of peritoneal Na and P removal. For Na, glucose concentration and usage of icodextrin were independent predictors, while for P dialysate volume and plasma phosphate concentrations were independent predictors.

Table 5.

Determinants of peritoneal Na and P removal as analysed by multivariable regression. All patients irrespective of the group were entered into the same model. SE standard error

Discussion

This study shows that different PD modalities can achieve fairly high and comparable removal of 80-120 mmol Na and 8-12 mmol P through the peritoneum per day. Peritoneal Na removal was slightly higher in CAPD than in APD, while there CAPD tended to have lower peritoneal P removal compared to APD. The combination of CAPD+APD achieved the highest values for both peritoneal Na and P removal compensating for the low residual renal function in these patients. Overall total Na and P removal were similar in the groups (180-220 mmol Na and 14-16 mmol P per day). The superiority of the peritoneal removal rates achieved with CAPD+APD is not a new finding and was characterized by Blake et al. in 1996 [15]. In that study, CAPD+APD with a mid-day change lead to higher clearance rate across all transporter types compared to APD with or without daytime filling which can be explained with the time-dependence of Na and P removal. In our center we commence this intensive treatment when residual function is strongly reduced in an APD patient, such as after several years on PD. Instead of a mid-day exchange we prescribe a 3-5 hours dwell time at the evening which is well feasible in patients after returning from their work. Our data show that this approach ensures high peritoneal removal rates compensating for reduced renal excretion that occurred in all groups over time. With combined CAPD+APD adequate PD can be re-accomplished in an APD patient enabling to continue PD and to benefit from the advantages of this home dialysis method.

Our study shows that treatment changes had an impact on peritoneal solute removal over time (table 4). These were most pronounced for ultrafiltration and Na elimination and to a lesser extent in peritoneal urea or creatinine elimination suggesting that routine Na monitoring helped to guide treatment and ensure adequate sodium balance. Treatment changes encompassed increased dialysate volume, higher glucose concentration and use of icodextrin. In patients with APD, cycler settings were optimized on an individual basis e.g. taking into account transporter status. Some patients were transferred to APD or CAPD+APD. Our data confirm that using icodextrin is of particularly great importance for peritoneal Na and to a lesser extent for P removal [10]. In APD patients and in those with reduced residual renal function icodextrin seems to be essential. Increasing glucose concentration could also work as it was also a determinant of higher peritoneal Na and to a lesser extent P removal. However, this will be limited by side effects of high glucose such as exacerbated hyperglycemia in diabetic patients, glucose overfeeding or peritoneal injury. In addition, high dialysate volume was found to be associated with damage to erythrocytes and eryptosis [16]. Interestingly, dialysate volume was an independent predictor only for P but not for Na removal. For P, plasma phosphorus concentration was also a highly significant predictor of peritoneal P removal that was has been reported earlier [17] and could be explained by an increased chemical gradient. This would also explain the highest peritoneal P removal in patients treated with CAPD+APD who at the same time had the highest plasma phosphorus values. This constellation indicates P retention in these patients despite higher removal. With regard to Na, CAPD+APD patients had the lowest values for overhydration measured with BCM (Fig. 2) that fit to the highest Na removal values. Therefore, it is important to analyse data on removal in combination with markers of retention such as overhydration or plasma P concentration to adequately assess solute homeostasis.

Weekly P removal on PD in our study was comparable to other studies [9, 13, 17]: we achieved 8-12 mmol (248-372 mg) per day corresponding to a weekly P dialysate clearance of 37 L/week in CAPD and 44 L/week in APD and CAPD+APD patients. These values are higher than that reported in a recent study comparing PD with HD [6]. The authors reported a weekly P dialysate clearance of only 33 L/week in a pooled sample of CAPD and APD patients that was significantly lower than in HD patients. This was driven by the extraordinary low clearance achieved with APD of 28 L/week whereas CAPD patients had a weekly clearance of 38 L/week. The reason for the low clearance on APD compared to our values must be related to the prescription. Unfortunately, that study did not report details on APD settings such as number of cycles, tidal volume or others or patient characteristics of the patients treated with APD. It mentions a high ultrafiltration suggesting a high number of cycles with short dwell times which is expected to result in lower P clearance. It is also conceivable that APD patients despite higher creatinine transporter status had low phosphorus transporter status and reduced phosphate transport [9, 13]. With our data, we can convincingly show that P removal is not necessarily inferior in APD patients and can be increased using CAPD+APD. Despite removal of 14-16 mmol P per day, dietary intake often exceeds this amount and was found to 20 mmol per day or higher in a peritoneal dialysis patient [18]. To avoid P retention this difference must be absorbed by phosphate binders. Thus, determination of P removal helps to calculate the required dose of P binders which also has to take into account binding capacity of the used P binders and the dietary intake.

The limitations of this study are due to its retrospective and character, its single-center character and the low number of PD patients. PD modality was not controlled and subject to confounding by indication such as CAPD+APD in those with reduced residual function. Therefore, the groups had significant differences in their characteristics which we adjusted for using ANCOVA. We are aware that an interventional study with a crossover design would have been superior to study the efficacy of each modality as done by Demetriuo et al. [19], but our goal was to analyse the values obtained in a real-life setting. Therefore, we were able to follow the time dependence from begin of the monitoring. Values for both peritoneal and renal Na and P removal showed great intra- and interindividual variability which is commonly encountered in studies examining solute clearance in PD [20, 21]. We addressed this by using a mixed model with time as independent variable and taking into account each replicate values of a patient.

Conclusion

Routine monitoring of Na and P removal increases awareness of maintaining Na and P balance in PD patients. Individualized adjustments of PD prescription including icodextrin use or higher glucose concentration can improve Na removal while P removal is mainly determined by the dialysate volume.

Disclosure Statement

The authors of this manuscript state that they do not have any conflict of interests and nothing to disclose.

Acknowledgments

We acknowledge the support by the Deutsche Forschungsgemeinschaft and the Open Access Publishing Fund of Tuebingen University.

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  17. Messa P, Gropuzzo M, Cleva M, Boscutti G, Mioni G, Cruciatti A, Mazzolini S, Malisan MR: Behaviour of phosphate removal with different dialysis schedules. Nephrol Dial Transplant 1998;13:S43-48.


  18. Jiang N, Fang W, Yang X, Zhang L, Yuan J, Lin A, Ni Z, Qian J: Dietary phosphorus intake and distribution in chinese peritoneal dialysis patients with and without hyperphosphatemia. Clin Exp Nephrol 2015;19: 694-700.


  19. Demetriou D, Habicht A, Schillinger M, Horl WH, Vychytil A: Adequacy of automated peritoneal dialysis with and without manual daytime exchange: A randomized controlled trial. Kidney Int 2006;70: 1649-1655.


  20. Steubl D, Roos M, Hettwer S, Angermann S, Wen M, Schmaderer C, Luppa P, Heemann U, Renders L: Comparison of peritoneal low-molecular-weight-protein-removal in ccpd and capd patients based on c-terminal agrin fragment clearance. Kidney Blood Press Res 2016;41: 175-185.


  21. Liu Y, Cheng BC, Lee WC, Li LC, Lee CH, Chang WX, Chen JB: Serum potassium profile and associated factors in incident peritoneal dialysis patients. Kidney Blood Press Res 2016; 41: 545-551.

Author Contacts

Ferruh Artunc, MD

Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology

and Nephrology, University Hospital of Tuebingen

Otfried-Mueller-Str. 10, 72076 Tuebingen (Germany)

Tel. +49-7071-2982711, Fax +49-7071-293174 E-Mail [email protected]


Article / Publication Details

First-Page Preview


Received: October 05, 2016
Accepted: February 21, 2017
Published online: May 25, 2017

Issue release date: June 2017


Number of Print Pages: 10

Number of Figures: 3

Number of Tables: 5


ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)


For additional information: https://www.karger.com/KBR


Open Access License / Drug Dosage / Disclaimer

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Renal Diet – NephCure Kidney International ®

People with compromised kidney function must adhere to a renal or kidney diet to cut down on the amount of waste in their blood. Wastes in the blood come from food and liquids that are consumed. When kidney function is compromised, the kidneys not filter or remove waste properly. If waste is left in the blood, it can negatively affect a patient’s electrolyte levels. Following a kidney diet may also help promote kidney function and slow the progression of complete kidney failure.

A renal diet is one that is low in sodium, phosphorous, and protein. A renal diet also emphasizes the importance of consuming high-quality protein and usually limiting fluids. Some patients may also need to limit potassium and calcium. Every person’s body is different, and therefore, it is crucial that each patient works with a renal dietitian work to come up with a diet that is tailored to the patient’s needs.

Below are some substances that are crucial to monitor to promote a renal diet:

Sodium

What is Sodium and its role in the body?

Sodium is a mineral found in most natural foods. Most people think of salt and sodium as interchangeable. Salt, however, is actually a compound of sodium and chloride. Foods we eat may contain salt or they may contain sodium in other forms. Processed foods often contain higher levels of sodium due to added salt.

Sodium is one of the body’s three major electrolytes (potassium and chloride are the other two). Electrolytes control the fluids going in and out of the body’s tissues and cells. Sodium contributes to:

  • Regulating blood pressure and blood volume
  • Regulating nerve function and muscle contraction
  • Regulating the acid-base balance of blood
  • Balancing how much fluid the body keeps or eliminates

Why should kidney patients monitor sodium intake?

Too much sodium can be harmful for people with kidney disease because their kidneys cannot adequately eliminate excess sodium and fluid from the body. As sodium and fluid build up in the tissues and bloodstream, they may cause:

  • Increased thirst
  • Edema: swelling in the legs, hands, and face
  • High blood pressure
  • Heart failure: excess fluid in the bloodstream can overwork your heart, making it enlarged and weak
  • Shortness of breath: fluid can build up in the lungs, making it difficult to breathe

How can patients monitor their sodium intake?

  • Always read food labels. Sodium content is always listed.
  • Pay close attention to serving sizes.
  • Use fresh, rather than packaged meats.
  • Choose fresh fruits and vegetables or no-salt-added canned and frozen produce.
  • Avoid processed foods.
  • Compare brands and use items that are lowest in sodium.
  • Use spices that do not list “salt” in their title (choose garlic powder instead of garlic salt.)
  • Cook at home and do NOT add salt.
  • Limit total sodium content to 400 mg per meal and 150 mg per snack.

Printable Low Sodium Diet Guidelines (PDF)

Potassium

What is Potassium and its role in the body?

Potassium is a mineral found in many of the foods we eat and is also found naturally in the body. Potassium plays a role in keeping the heartbeat regular and the muscles working correctly. Potassium is also necessary for maintaining fluid and electrolyte balance in the bloodstream. The kidneys help to keep the right amount of potassium in your body and they expel excess amounts into the urine.

Why should kidney patients monitor their potassium intake?

When the kidneys fail, they can no longer remove excess potassium, so potassium levels build up in the body. High potassium in the blood is called hyperkalemia which can cause:

  • Muscle weakness
  • An irregular heart beat
  • Slow pulse
  • Heart attacks
  • Death

How can patients monitor their potassium intake?

When the kidneys no longer regulate potassium, a patient must monitor the amount of potassium that enters the body.

Tips to help keep the levels of potassium in your blood safe, make sure to:

  • Talk with a renal dietitian about creating an eating plan.
  • Limit foods that are high in potassium.
  • Limit milk and dairy products to 8 oz per day.
  • Choose fresh fruits and vegetables.
  • Avoid salt substitutes & seasonings with potassium.
  • Read labels on packaged foods & avoid potassium chloride.
  • Pay close attention to serving size.
  • Keep a food journal.

Printable Low Potassium Diet Guidelines (PDF)

Phosphorus

What is Phosphorus and its role in the body?

Phosphorus is a mineral that is critical in bone maintenance and development. Phosphorus also assists in the development of connective tissue and organs and aids in muscle movement. When food containing phosphorus is consumed and digested, the small intestines absorb the phosphorus so that it can be stored in the bones.

Why should kidney patients monitor Phosphorus intake?

Normal working kidneys can remove extra phosphorus in your blood. When kidney function is compromised, the kidneys no longer remove excess phosphorus. High phosphorus levels can pull calcium out of your bones, making them weak. This also leads to dangerous calcium deposits in the blood vessels, lungs, eyes, and heart.

How can patients monitor their Phosphorus intake?

Phosphorus can be found in many foods. Therefore, patients with compromised kidney function should work with a renal dietitian to help manage phosphorus levels.

Tips to help keep phosphorus at safe levels:

  • Know what foods are lower in phosphorus.
  • Pay close attention to serving size
  • Eat smaller portions of foods that are high in protein at meals and for snacks.
  • Eat fresh fruits and vegetables.
  • Ask your physician about using phosphate binders at meal time.
  • Avoid packaged foods that contain added phosphorus. Look for phosphorus, or for words with “PHOS” on ingredient labels.
  • Keep a food journal

Printable Low Phosphorus Diet Guidelines (PDF)

Protein

Protein is not a problem for healthy kidneys. Normally, protein is ingested and waste products are created, which in turn are filtered by the nephrons of the kidney. Then, with the help of additional renal proteins, the waste turns into urine. In contrast, damaged kidneys fail to remove protein waste and it accumulates in the blood.

The proper consumption of protein is tricky for Chronic Kidney Disease patients as the amount differs with each stage of disease. Protein is essential for tissue maintenance and other bodily roles, so it is important to eat the recommended amount for the specific stage of disease according to your nephrologist or renal dietician.

Fluids

Fluid control is important for patients in the later stages of Chronic Kidney Disease because normal fluid consumption may cause fluid build up in the body which could become dangerous. People on dialysis often have decreased urine output, so increased fluid in the body can put unnecessary pressure on the person’s heart and lungs.

A patient’s fluid allowance is calculated on an individual basis, depending on urine output and dialysis settings. It is vital to follow your nephrologist’s/nutritionist’s fluid intake guidelines.

To control fluid intake, patients should:

  • Not drink more than what your doctor orders
  • Count all foods that will melt at room temperature (Jell-O®, popsicles, etc.)
  • Be cognizant of the amount of fluids used in cooking

90,000 Soil scientists at RUDN University visualized how plants obtain phosphorus from soil

Soil scientists at RUDN University for the first time were able to visualize the activity of the phosphatase enzyme in the soil at the roots of a plant through the simultaneous use of zymography and a fiber-optic acidity sensor. This helped them see how the plants “adjust” the root system to the environment. The research is published in the journal Soil Biology and Biochemistry.

Phosphorus is necessary for most metabolic processes in plants, but in the soil it is often inaccessible to them, since it forms insoluble complexes, for example, with aluminum, iron and calcium, and microorganisms include it in organic compounds. Deficiency of this element reduces yields, while organic and mineral phosphate fertilizers can be expensive and negatively affect the environment.

Soil scientist from RUDN University Yakov Kuzyakov, head of the University Center for Mathematical Modeling and Forecasting of Sustainable Ecosystems, for the first time was able to observe how plants adapt to the deficiency or absence of phosphorus in the soil.

Researchers have experimented with white lupine – a plant that develops in symbiosis with nodule bacteria – they help it absorb nutrients. Lupine seeds were germinated and sown in risoboxes – containers with dried loess limestone rock mixed with sand.Rhizoboxes were divided into three types: without phosphorus, with the addition of sodium phytate – this is one of the important forms of phosphorus in animal manure – and with the addition of calcium dihydrogen phosphate.

The soil scientist monitored the state of plant roots and surrounding soil in each container using the electrochemical method of studying the activity of enzymes – zymography. This method was necessary to visualize the activity of acid and alkaline phosphatases – plant enzymes that break down phosphoric acid and help plants get phosphorus from it.Their activity depends on the development of plants and their interaction with microorganisms-symbionts, as well as on the acidity of the soil. If the medium is acidic, acidic phosphatase “works”, and at low acidity, alkaline “turns on”. In each of the risoboxes, there was also a fiber-optic soil acidity sensor to observe how the degree of phosphorus availability affects this indicator.

Measurements were carried out after 11 and 24 days, that is, before and after the formation of a developed root system. Before the formation of branches around the taproot in a container with a phosphorus deficiency, the activity of acid phosphatases was increased, the rhizosphere, the root growth zone, was expanded, and the acidity of the soil in it was increased.The fact is that in the absence of phosphorus, the roots of the plant began to release hydrogen ions – protons, which increased the acidity of the soil. The increase in acidity, in turn, promoted the work of acid phosphatases, which release phosphorus. This did not affect the work of alkaline phosphatases.

After the appearance of a branched root system, the zone where the presence of enzymes was recorded increased, due to which the volume of soil from which the plant tried to extract phosphorus increased. Therefore, the lupine no longer had to emit so many protons, and the acidity of the soil was average.As a result, the activity of acidic and alkaline phosphatases became approximately the same. Thus, in the first experimental risobox, where a phosphorus deficiency was initially created, lupine “invested” energy not in the growth of aerial shoots, but in the growth of roots, which provided a large area of ​​enzyme activity for 24 days.

In the second rhizobox with the addition of sodium phytate to the formation of adventitious roots, a reduced activity of phosphatases and a smaller zone of the rhizosphere were observed. The fact is that phytates under these conditions were transformed into phosphorus available to plants, and lupine was not deficient in it.Therefore, the roots produced fewer protons, and the acidity was not so high.

Approximately the same picture was observed in the third rhizobox – with the addition of calcium dihydrogen phosphate. However, the degree of enzymatic activity, both acidic and alkaline, in the rhizosphere of the third sample on the 24th day was higher than in others. This is because a sufficient amount of phosphorus stimulates plant growth and the release of carbon into the soil. Therefore, there are more products that the roots release into the rhizosphere when calcium dihydrogen phosphate is added, and they contribute to the growth of soil microorganisms and the synthesis of enzymes.

Research has shown that the availability of phosphorus underground, root morphology, enzyme activity and soil acidity are interrelated. The use of two methods, zymography and measurement of acidity, made it possible for the first time to trace this connection. It turned out that as the root system develops, taproots lose their importance for phosphorus mobilization. Lack of phosphorus stimulates plants to acidify the rhizosphere and activate acid phosphatases. With a reduced acidity, roots and microorganisms produce less acid phosphatase.And since the acidity of the soil changes with the development of the root system, acid phosphatase shows strong temporal variability in its contribution to the phosphorus supply of lupine. Alkaline phosphatase, on the other hand, ensures a more constant mobilization of phosphorus during the entire period of growth of the plant’s root system.

Work in Soil Biology and Biochemistry

Minerals | Tervisliku toitumise informatsioon

More than 70 chemical elements have been found in the human body.The need for more than 20 bioelements has been reliably established. In order to ensure sufficient amounts of these elements, it is imperative that the diet is varied.

The minerals found in the body can be conditionally divided into two groups:
  • The content of macronutrients in the body is more than 0.01%. They are phosphorus (P), calcium (Ca), sodium (Na), potassium (K), magnesium (Mg), sulfur (S), chlorine (Cl) (see Table 1) .
  • The content of trace elements is less than 0.01%, some even 0.00001.

The need for some trace elements has been established, these are iron (Fe), zinc (Zn), copper (Cu), iodine (I), selenium (Se), manganese (Mn), molybdenum (Mo), fluorine (F), chromium (Cr), cobalt (Co), silicon (Si), vanadium (V), boron (B), nickel (Ni), arsenic (As) and tin (Sn).

In addition to them, a number of elements have been found in the body, the function of which is not yet clear, their appearance in the body may be due to environmental pollution and frequent contact with them. For example, people working in greenhouses are constantly in contact with chemicals, various elements can be a sign of various kinds of diseases.These elements include aluminum (Al), strontium (Sr), barium (Ba), rubidium (Rb), palladium (Pd), bromine (Br).

The body can also get heavy, i.e. poisonous metals such as cadmium (Cd), mercury (Hg) or lead (Pb).

Minerals in our body are important components of the skeleton, biological fluids and enzymes and contribute to the transmission of nerve impulses.

People and animals receive various biological elements from food, water and ambient air , living organisms cannot synthesize mineral substances on their own.In plants, minerals accumulate from the soil, and their amount depends on the place of growth and the availability of fertilizers. Drinking water also contains minerals, and their content depends on the place where the water is obtained from.

Despite the fact that a person needs small amounts of minerals (macronutrients in milligrams and grams, microelements in milligrams and micrograms), his body, nevertheless, lacks sufficient reserves of minerals to normally tolerate their long-term deficiency …The need for minerals also depends on age, gender and other circumstances (see Table 2) . For example, the increased need for iron in women is associated with menstruation and pregnancy, and athletes need more sodium because it is excreted intensively in sweat.

Excessive amounts of minerals can lead to malfunctions in the body, because, being components of bioactive compounds, they affect regulatory functions. It is almost impossible to get excessive amounts of minerals (with the exception of sodium) from food, but this can happen with excessive use of dietary supplements and mineral-fortified foods.

Mineral absorption may be hindered by:
  • coffee abuse,
  • drinking alcohol,
  • smoking,
  • certain medications,
  • certain birth control pills,
  • certain substances found in certain foods, such as rhubarb and spinach …

The loss of minerals during the heat treatment of food is significantly less than the loss of vitamins. However, during refining or refining, some of the minerals are removed.Therefore, it is important to eat more whole grains and unrefined foods. Minerals can form compounds with other substances found in food (for example, with oxalates in rhubarb), as a result of which the body cannot absorb them.

Table 1
Names and sources of the most important mineral substances

iodine

Designation

Name

Best sources *

Macroelements

sodium

table salt (NaCl), prepared food, cheese, rye bread, canned food, meat products, olives, potato chips

K

potassium

vegetable products: dried fruits and berries, nuts, seeds, Jerusalem artichoke, potatoes, radishes, cabbage, green vegetables, Kama flour, beets, banana, rye bread, currants, tomatoes

Ca

calcium

milk and dairy products (especially cheese), almonds, ore hee, seeds, fish (with bones), spinach

Mg

magnesium

nuts, seeds, Kama flour, rye bread, spinach, legumes, buckwheat, whole grains, pork, beef and chicken, banana, broccoli

P

phosphorus

seeds, nuts, dairy products (especially cheese), liver, poultry, beef, rye bread, fish, whole grains products, legumes

S

sulfur

products with proteins containing the amino acids methionine (cereals, nuts) and cysteine ​​(meat, fish, soybeans, cereals)

Cl

chlorine

table salt

Trace elements

Fe

Iron

liver, blood sausage, seeds, eggs, raisins, rye bread, lean beef and pork, whole grains, buckwheat, strawberries

n

0

zinc

liver, meat, Kama flour, seeds, nuts, cheese, rye bread, legumes, seafood (crabs, herring), whole grain products, eggs

Cu

copper

liver, cocoa powder, meat, legumes, whole grains, seeds, nuts, buckwheat, rye bread, salmon, avocado, beets, seafood

I

iodized salt, fish and other seafood, cheese, eggs, some types of rye bread and yoghurt

Se

selenium

peanuts, liver, fish and seafood, sunflower seeds, meat

* The amount contained in 100 g of the product covers at least 10% of the daily requirement of an adult woman

Table 2
Recommended depending on age, daily intake of the most important minerals

9 0081

320

9000 9008 9002 3.1

900 81

175

10

Age

Sodium, mg

Calcium, mg

Potassium, g

Magnesium, mg

Iron , mg

Zinc, mg

Copper, mg

Iodine, μg

Selenium, μg

Children

6-11 months

to 650

550

1,1

8084

9000

8

5

0.3

60

15

12-23 months

to 830

600

, 4

85

8

6

0.3

90

25

2-5 years

to

600

1.8

120

8

6

0.4

90

30

6-9 years

to 1580

700

2

4 200

9

7

0.5

120

30

Women

10-13 years

to 2400

9002 900

981

300

11

8

0 , 7

150

40

14-17 years

to 2400

900

3.1

320

9

0.9

150

50

18-30 years

to 2400

900

900.1

320

15

9

0.9

150

50

31-60 years

9002 to 24

800

3.1

320

15

9

0.9

150

50

61-74 years

to 2400

800

3.1

320

4 9003 10 9000

9

0.9

150

50

> 75 years

to 2400

800

3.1

10

9

0.9

150

50

Pregnant

to 2400

360

15

10

1

60

Breastfeeding mothers

to 2400

900

3.1

360

15

1.3

200

60

Men

9000

10-13 years

to 2400

900

3.3

300

11

0.7

9000 2 150

40

14-17 years

to 2400

900

3.5

380

11

9000

0.9

150

60

18-30 years

to 2400

900

3.5

10

9

0.9

150

60

31-60 years

to 2400

3.5

380

10

9

0.9

150 900 03

60

61–74 years

to 2400

800

3.5

380

10

10

0.9

150

60

> 75 years

to 2400

800

3.5

380

10

0.9

150

60

* For 18-20 year olds, the recommended daily intake is 900 mg calcium and 700 mg phosphorus.
** The need for iron depends on the loss of iron during menstruation. For postmenopausal women, the recommended daily intake of iron is 10 mg.
*** To achieve a balanced iron content during pregnancy, a woman’s body must have at least 500 mg more iron stores than before pregnancy. In the last two trimesters of pregnancy, depending on the level of iron in the body, additional iron supplementation may be required.
**** In fact, selenium can be consumed more than the recommended dose indicated in the table, since selenium is absorbed differently from different sources and there is a constant depletion of the surface, i.e.That is, the nutritional value tables of products “do not keep up” with the true state of affairs (they often indicate values ​​greater than the real ones).

Maximum single safe doses of minerals and food additives:
Mineral substance Dose
Calcium (mg) 2500
Phosphorus (mg) 3000
Potassium ( mg) 3.7 *
Iron (mg) 60
Zinc (mg) 25
Copper (mg) 5
Iodine (μg) 600
Selenium (μg) 300

* Only from dietary supplements or fortified foods

Phosphorus.General information

Phosphorus is contained in a wide range of organic and inorganic compounds, it is one of the essential elements of the composition of all cells and tissues of animals and plants. The body of an adult contains about 600 g of phosphorus, 85% of this amount is present in bone tissue, where phosphorus, along with calcium, in the composition of hydroxylapatite is a mineral phase. Phosphorus of bone tissue can pass into the intra- and extracellular pool of the body.In the cells of other tissues, phosphorus is found in a variety of organic molecules – nucleic acids (DNA, RNA), phospholipids, high-energy compounds (ATP, ADP, creatine phosphate), coenzymes involved in extremely important metabolic processes. Intracellular phosphorus is an essential component necessary for the regulation of the metabolism of proteins, fats and carbohydrates, cell growth and gene transcription. Serum contains mainly inorganic phosphorus compounds in the form of monovalent (h3PO4 -) and divalent anions (HPO42-) in free and protein-bound form, and also in the form of sodium, calcium and magnesium salts.The determination of inorganic phosphorus is of the greatest diagnostic value.

The daily requirement for phosphorus in adults is 1000–2000 mg; there is practically no phosphorus deficiency in food. Phosphorus absorption is greatest in the jejunum. A decrease in the activity of this process was noted under conditions of increased acidity of gastric juice, taking certain medications (aluminum hydroxide), with an increase in calcium content in food due to the formation of insoluble compounds with phosphorus in the intestine.

Normally, in adults, most of the phosphorus absorbed in the intestine is eliminated by the kidneys. About 90% of phosphorus in the blood passes through the glomerular membrane, ending up in the primary urine, then phosphates are almost completely reabsorbed in the proximal nephron tubules, and additional phosphate secretion occurs in the distal tubules.

The exchange of phosphorus in the body is closely related to the exchange of calcium. The main factors that regulate phosphate and calcium metabolism include PTH, calcitonin, and vitamin D.

PTH reduces the amount of inorganic phosphorus in the blood, activating its excretion by the kidneys. With overproduction of PTH, inhibition of phosphorus reabsorption is noted and, consequently, an increase in its excretion. Primary hypoparathyroidism is characterized by hyperphosphatemia.

1,25-dihydroxycholecalciferol – the active form of vitamin D3, increases the absorption of inorganic phosphates in the intestine and the reabsorption of phosphorus in the renal tubules.

The physiological role of calcitonin is determined by its participation in the regulation of calcium and phosphate metabolism in the body; its action is carried out with the participation of parathyroid hormone and the active form of vitamin D.

In the diagnosis of metabolic disorders of inorganic phosphorus, it is recommended to simultaneously determine its concentration in the blood and urine.

Nitrogen, phosphorus – SSC MSU

Lesson 9. Individual work.

Synthesis of nitrogen and phosphorus compounds

♦ I. Nitrogen oxides and acids

Nitrous anhydride (method 1)

Place 3-4 g of starch in a small flask or Würz tube and supply it with a dropping funnel with 10 ml conc.HNO 3 . Attach two U-shaped tubes to the flask, in the first of which place a desiccant, and immerse the second in the cooling mixture.

Add nitric acid dropwise to the starch. If reaction does not proceed, gently heat the flask.

Pour some of the liquid nitrous anhydride into a glass of ice water. Prove which ions are present in the solution.

Jobs

1. What is starch for?

2. What should be used as a desiccant?

3.Which refrigerant mixture should I use?

4. Where is the product collected?

5. What is the difference between the composition of the gas and the composition of the liquid product?

6. What happens when the product is poured into hot and cold water? How to prove it?

Nitrous anhydride (method 2)

Add 5 M sulfuric acid solution dropwise to cold concentrated sodium nitrite solution. Observe the ongoing changes.

Jobs

1.Why does the sodium nitrite solution need to be cooled?

2. How should the sodium nitrite solution be cooled?

3. Why is sulfuric acid of exactly this concentration used (not concentrated and not diluted)?

Nitrogen oxide (IV)

Place 5-7 g of lead nitrate mixed with clean sand in a 1: 1 volumetric ratio into a test tube. Close the tube with a stopper with a gas outlet tube. Connect it to two U-pipes, in the first of which place a desiccant, and the second immerse in the refrigerant mixture.

Heat the tube with lead nitrate.

Pour part of liquid nitrogen oxide into ice water. Check which ions are in the solution.

Jobs

1. What should be used as a desiccant?

2. Which refrigerant mixture should I use?

3. Where is the product collected?

4. What is the difference between the composition of the gas and the composition of the liquid product?

5. What is formed by the interaction of nitric oxide (IV) with cold and hot water? How can I check this?

6.Why is sand added to lead nitrate?

Fuming nitric acid

Put 15 g of sodium nitrate into the retort and pour through the funnel inserted into the tube, as many conc. H 2 SO 4 to cover the salt. Close the tube with an asbestos stopper and lower the throat of the retort into a dry receiver cooled by snow. Heat the retort carefully.

Pour the distilled nitric acid into a weighed flask with a stopper and determine the output.

Pour some of the acid produced into a porcelain cup and throw a piece of hot charcoal into it.

Jobs

1. Why can’t the tube be closed with a rubber stopper?

2. Why do they take crystalline sodium nitrate and a concentrated solution of sulfuric acid, and not dilute solutions of these substances?

3. Why is the reaction carried out at low heating?

4. Why can the obtained acid be colored?

5.What other properties of fuming nitric acid could you demonstrate? Write 2-3 reactions.

ICSC 1045 – SODIUM CHLORITE

ICSC 1045 – SODIUM CHLORITE

SODIUM CHLORITE ICSC: 1045 (April 2000)


CAS #: 7758-19-2
UN #: 1496
EINECS #: 231-836-6

SPECIAL HAZARDS PREVENTIVE MEASURES FIRE EXTINGUISHING
FIRE AND EXPLOSION Not flammable, but will ignite other substances.In case of fire, gives off irritating or toxic fumes (or gases). Risk of explosion on contact with reducing agents or organic materials. DO NOT allow contact with flammable or reducing agents. Use plenty of water, water spray. DO NOT use carbon dioxide. In case of fire: cool drums, etc. spraying water.

PREVENT DUST FORMATION!
SYMPTOMS PREVENTIVE MEASURES FIRST AID
Inhalation Cough.Sore throat. Use ventilation (if not powder), local exhaust, or respiratory protection. Fresh air, peace.
Leather Redness. Pain. Protective gloves. First rinse with plenty of water for at least 15 minutes, then remove contaminated clothing and rinse again.
Eyes Redness. Pain. Wear protective goggles. First rinse with plenty of water for several minutes (remove contact lenses if easy to do), then seek medical attention.
Ingestion Abdominal pain. Vomit. Do not eat, drink or smoke while working. Wash your hands before eating. Rinse mouth. Induce vomiting (ONLY IN CONSCIOUSNESS!).Seek medical attention.

SPILLAGE DISPOSAL CLASSIFICATION AND MARKING
Personal protection: Particulate filter respirator suitable for airborne concentrations. Sweep spilled substance into closed containers. If necessary, wet first to avoid dust build-up. Carefully collect the remainder.Then store and dispose of in accordance with local regulations. DO NOT cover with sawdust or other flammable absorbents.

According to UN GHS criteria

Transport
UN Classification
UN Hazard Class: 5.1; UN Pack Group: II

STORAGE
Separated from combustible substances, reducing agents, acids and incompatible materials.See chemical hazards. Cool place. Keep dry. Store in a well ventilated area.
PACKAGING

Background information in English prepared by a group of international experts working on behalf of the ILO and WHO with financial support from the European Union.
© ILO and WHO 2018

SODIUM CHLORITE ICSC: 1045
PHYSICAL AND CHEMICAL PROPERTIES

Aggregate Condition; Appearance

SLIGHTLY HYGROSCOPIC WHITE CRYSTALS OR FLAKES.

Physical hazards

Chemical hazards

decomposes at 200 ° C. This produces toxic and corrosive fumes. Creates a fire and explosion hazard. The substance is a strong oxidizing agent. Reacts actively with combustible materials and reducing agents. Reacts intensely with acids, ammonium compounds, phosphorus, sulfur and sodium dithionate. Creates an explosion hazard.

Formula: NaClO 2
Molecular weight: 90.44

Decomposes at 180-200 ° C
Density: 2.5 g / cm³
Solubility in water, g / 100 ml at 17 ° C: 39

EFFECTS ON THE BODY AND EFFECTS OF EXPOSURE

Exposure routes

The substance can be absorbed into the body by inhalation as an aerosol and by ingestion.

91 463 Effects from short-term exposure 91 464

The substance is irritating to the eyes, the skin and the respiratory tract.

Risk of inhalation

Evaporation at 20 ° C is negligible; however, a harmful concentration of airborne particles can be reached quickly when sprayed, especially when powdered.

91 463 Effects from prolonged or repeated exposure 91 464

Maximum allowable concentration

ENVIRONMENT

NOTES
Acquires shock sensitivity when contaminated with organic materials.
Wash contaminated clothing with copious amounts of water due to fire hazard.

ADDITIONAL INFORMATION

EU Classification

(en) Neither the ILO, WHO, nor the European Union are responsible for the quality and accuracy of the translation or for the possible use of this information.
© Version in Russian, 2018

Phosphorus, random urine, with creatinine and phosphorus / creatinine ratio calculation

Interpretation of results

Interpretation of test results contains information for the attending physician and does not constitute a diagnosis.The information in this section cannot be used for self-diagnosis and self-medication.
An accurate diagnosis is made by a doctor, using both the results of this examination and the necessary information from other sources: anamnesis,
results of other examinations, etc.

Units and conversion factors:

Units of measurement in INVITRO:

Urine phosphorus, concentration: mmol / l

Creatinine of urine, concentration: mmol / l

Phosphorus / creatinine ratio: mmol / mmol creatinine

Alternative units:

Urine phosphorus, concentration: mg / dl (conversion: mg / dl * 0.323 => mmol / l).

Urine creatinine, concentration: mg / dl (recalculation: mg / dl * 0.0884 => mmol / l).

Phosphorus / creatinine ratio: mmol / g creatinine (conversion: mmol / g creatinine * 0.113 => mmol / mmol creatinine).

Reference values:

Phosphorus concentration: No reference values ​​provided.

Creatinine concentration: No reference values ​​provided.

Phosphorus / creatinine ratio:

Age Phosphorus / creatinine ratio, mmol / mmol creatinine
<6 months 1.4-20.0
6-12 months 1.4-18.0
1-2 years 1.2-14.0
2-3 years 1.2-12.0
3-5 years 1.2-8.0
5-7 years 1.2-5.0
7-10 years 1.2-3.6
10- 14 years old 0.8-3.2
14-17 years old 0.8-2.7
Men

<40 years
> 40 years

0.1-6.5

0.2-3.1
Women

<40 years
> 40 years

0.4-3.4

0.4-3.9

Note: If the level of phosphorus in the sample is below the detection limit of the method, the calculation of the phosphorus / creatinine ratio is not possible (the result is displayed as “UNCALCULATED”).

Interpretation of the result:

The results of urine analysis are interpreted in conjunction with the analysis of the clinical situation and the results of other laboratory studies.

Increasing values:

  1. Hyperparathyroidism.
  2. Vitamin D-resistant rickets.
  3. Immobilization after paraplegia or fracture.
  4. Intoxication with vitamin D.
  5. Damage to the renal tubules (eg, Fanconi syndrome).
  6. Familial hypophosphatemia.
  7. Nonrenal acidosis (increased excretion of phosphate as a buffer in urine).
  8. Medicines: acetazolamide, L-alanine, asparaginase, aspirin, bicarbonates, bismuth salts, calcitonin, corticosteroids, dihydrotachysterol, hydrochlorothiazide, metolazone, phosphates, parathyroid hormone, tryptophan, valine, vitamin D.

Derating:

  1. Hypoparathyroidism.
  2. Pseudohypoparathyroidism.
  3. Parathyroidectomy.
  4. Medicines: alanine, aluminum-containing antacids, mannitol (chemical interference in research).

Literature

  1. Pediatric Nephrology. A Practical Guide (ed. By E. Loimann, A.N. Tsygin, A.A. Sarkisyan). M., Litterra, 2010, 400 p.
  2. Mazo AM et al. – Fractional excretion of sodium and lithogenic substances in urine in children with urolithiasis. Nephrology and dialysis, 2010, v.12, No. 4. 299-303.
  3. Yurieva EA, Dlin VV, Kudin MV, et al. Metabolic nephropathy in children: causes of development, clinical and laboratory manifestations.Russian Bulletin of Perinatology and Pediatrics. 2016, 2, pp. 28-34.
  4. Sakhaee K., Maalouf N. M., Sinnott B. – Kidney Stones 2012: Pathogenesis, Diagnosis, and Menagement. – J Clin Endocrinol Metab., 2012, Vol. 97, p.p. 1847-1860.
  5. Tasian E., Copelovitch L. – Evaluation and Medical Management of Kidney Stones in Chidren. J Urol. 2014, Vol. 192, No 5, p.p. 1329-1336.
  6. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics.4 ed. Ed. Burtis C.A., Ashwood E.R., Bruns D.E., Elsevier, New Delhi, 2006, 2412 p.
  7. Materials of the manufacturer of reagents.

Inorganic phosphorus (S-P) – SYNLAB Eesti

In the body of an adult, about 700 g of phosphate, of which 85% is located in the bone tissue in the form of inorganic phosphate. In the blood, organic phosphate is mainly found intracellularly in the composition of energy-rich compounds such as ATP, as well as AMP and NADP.Phosphate is also important for the activation of certain enzymes.

Inorganic phosphate of blood serum is represented by di- and monovalent free anions (55%), their ratio depends on blood pH. About 10% of whey phosphate is bound to proteins and about 35% is complexed with calcium, magnesium and sodium.

Serum inorganic phosphate is measured for routine phosphate determination.

The body receives phosphate from food.In the intestine, in the presence of vitamin D, 60-80% of phosphate is absorbed. Phosphate freely passes the glomerular filter and more than 80% is reabsorbed in the proximal renal tubules along with sodium ions. Tubular phosphate reabsorption is regulated by parathyroid hormone.

Readings:

  • Diseases of the parathyroid glands
  • Vitamin D metabolic disorders
  • Bone diseases
  • Renal failure

Method of analysis: Photometry

Reference value: 0.78-1.65 mmol / L

Result interpretation:

Hyperphosphatemia:

  • Decreased excretion (most common cause is renal failure)
  • Hypoparathyroidism, acromegaly, Addison’s disease
  • Excess vitamin D intake
  • Tissue catabolism (multiple myeloma, osteoporosis, tumor breakdown)

Hypophosphatemia – relatively common:

  • Decreased intestinal absorption: malabsorption syndrome, vitamin D deficiency, primary and secondary hyperparathyroidism
  • Accelerated excretion of phosphate: damage to renal tubules
  • Phosphate-poor enteral / parenteral nutrition, improving phase diabetic ketoacidosis, alcohol dependence treatment, alkalosis (mainly respiratory)

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