Nutritional Management of Renal Disease

Joel D. Kopple, Shaul G Massry, Kamyar Kalantar-Zadeh

• Publisher: Academic Press
• Year: 2012
• eBook ISBN: 9780123919359
• Edition: 3
• Topic: Technology & Engineering
• Subtopic: Pharmacology
• Index: Technology & Engineering

This translational text offers in-depth reviews of the metabolic and nutritional disorders that are prevalent in patients with renal disease. Chapter topics address the growing epidemic of obesity and metabolic syndrome. Each chapter integrates basic and clinical approaches, from cell biology and genetics to diagnosis, patient management and treatment. Chapters in sections 4-7 include new illustrative case reports, and all chapters emphasize key concepts with chapter-ending summaries. New features also include the latest National Kidney Foundation Clinical Practice Guidelines on Nutrition in Chronic Renal Failure, the most recent scientific discoveries and the latest techniques for assessing nutritional status in renal disease, and literature reviews on patients who receive continuous veno-venous hemofiltration with or without dialysis. - Provides a common language for nephrologists, nutritionists, endocrinologists, and other interested physicians to discuss the underlying research and translation of best practices for the nutritional management and prevention of renal disease - Saves clinicians and researchers time in quickly accessing the very latest details on nutritional practice as opposed to searching through thousands of journal articles - Correct diagnosis (and therefore correct treatment) of renal, metabolic, and nutritional disorders depends on a strong understanding of the molecular basis for the disease – both nephrologists and nutritionists will benefit - Nephrologists and nutritionists will gain insight into which treatments, medications, and diets to use based on the history, progression, and genetic make-up of a patient - Case Reports will offer an added resource for fellows, nutritionists, and dieticians who need a refresher course

Chapter 1

The Influence of Kidney Disease on Protein and Amino Acid Metabolism

B. Workeneh and William E. Mitch

Baylor College of Medicine, Nephrology Division, Department of Medicine, Houston, TX, USA

Introduction

Epidemic analyses reveal that chronic kidney disease (CKD) is associated with defects in many metabolic processes. It should not be surprising therefore, that among the defects are abnormalities in protein and amino acid metabolism. In this chapter, we will identify specific abnormalities in protein and amino acid metabolism and will discuss interventions to stop or attenuate the loss of protein stores that occurs in patients with CKD. Besides the intellectual satisfaction of learning how CKD stimulates the loss of body weight and influences the “intracellular milieu”, we believe that understanding mechanisms which underlie metabolic abnormalities in protein and amino acids is the first step towards devising strategies to block or ameliorate such defects. For example, after the protein and amino acid catabolism caused by acid accumulation were uncovered, investigators demonstrated the salutary effects of correcting acidosis in CKD patients (Table 1.1) [1–4]. Not only does treating metabolic acidosis suppress the protein wasting stimulated by CKD but it was recently reported that correcting acidosis in CKD patients can even slow their loss of kidney function [5].

TABLE 1.1 Evidence that Metabolic Acidosis Induces Protein and Amino Acid Catabolism in Normal Infants and Children, as well as, CKD Patients

Subjects Investigated	Measurements of Effectiveness	Outcome of Trial
Infants [131]	Low birth weight, acidotic infants were given NaHCO3 or NaCl	NaHCO3 supplement improved growth
Children [132] with CKD	Children with CKD had protein degradation measured	Protein loss was ~ 2-fold higher when HCO3 was < 16 mM compared to > 22.6 mM
Normal adults [126]	Induced acidosis and measured amino acid and protein metabolism	Acidosis increased amino acid and protein degradation
Normal adults [133]	Induced acidosis and measured nitrogen balance and albumin synthesis	Acidosis induced negative nitrogen balance and suppressed albumin synthesis
Chronic kidney disease [134]	Nitrogen balance before and after treatment of acidosis	NaHCO3 improved nitrogen balance
Chronic kidney disease [5]	Two years NaHCO3 therapy vs. standard care	Slowed loss of creatinine clearance and improved nutritional status
Chronic kidney disease [81]	Essential amino acid and protein degradation before and after treatment of acidosis	NaHCO3 suppressed amino acid and protein degradation
Chronic kidney disease [135]	Muscle protein degradation and degree of acidosis	Proteolysis was proportional to acidosis and blood cortisol
Chronic kidney disease [136]	Nitrogen balance before and after treatment of acidosis	NaHCO3 reduced urea production and nitrogen balance
Hemodialysis [137]	Protein degradation before and after treatment of acidosis	NaHCO3 decreased protein degradation
Hemodialysis [138]	Serum albumin before and after treatment of acidosis	NaHCO3 increased serum albumin
CAPD [139]	Protein degradation before and after treatment of acidosis	NaHCO3 decreased protein degradation
CAPD [45]	Weight and muscle gain before and after treatment of acidosis	Raising dialysis buffer increased weight and muscle mass

Another example of the relevance of abnormal protein metabolism to the care of patients with CKD arises from the familiar relationship between low values of serum albumin and mortality in dialysis patients. The low values of serum albumin have generally been attributed to eating an inadequate diet, i.e., were suffering from malnutrition [6]. This diagnosis is erroneous for the following reasons. First, if protein malnutrition was the cause of defects in protein stores, then low values of serum albumin should be corrected by simply altering the diet. Although careful attention to the diet is absolutely required, there should be additional strategies directed at inhibiting processes causing muscle wasting. Ikizler and colleagues measured protein synthesis and degradation in fasting hemodialysis patients using standard techniques of labeled amino acid turnover [7]. Specifically, they measured the components of protein metabolism before, during and at 2 hours after completing the dialysis treatment. At all three points, protein degradation exceeded protein synthesis suggesting that the dialysis procedure can activate metabolic pathways that stimulate the loss of body protein stores. Subsequently, the investigators tested the influence of providing intravenous parenteral nutrition (IDPN) during hemodialysis and making the same measurements [8]. When given during dialysis, the IDPN supplement improved both protein synthesis and degradation but at two hours after dialysis there was a persistent increase in protein degradation. Thus, abnormalities in protein metabolism were not eliminated by simply infusing amino acids and calories during dialysis. In a third evaluation, the investigators compared the responses associated with administration of IDPN to those induced by an oral nutritional supplement given during hemodialysis. Protein balance improved with both IDPN and the oral supplement. At two hours after completing dialysis, whole body protein balance was still negative, though forearm muscle protein balance was improved [9]. These careful studies indicate that dialysis must activate or stimulate catabolic pathways in CKD patients, increasing the risk of muscle protein wasting. In addition, the results indicate that the unidentified, catabolic pathways are not “turned off” by increasing dietary constituents. Others report similar conclusions: in a randomized, controlled trial, IDPN was given to hemodialysis patients and compared to results obtained in patients not receiving a dietary supplement [10]. After two years, the supplement had improved the serum concentration of albumin. Unfortunately, the supplement did not improve mortality, body mass index, laboratory markers of nutritional status or the rate of hospitalization. Taken together, these reports suggest that correcting metabolic abnormalities induced by CKD or at least blunting their physiologic influence should be explored because new therapies need to be developed to counteract catabolic responses.

CKD Interrupts the Components of Protein Metabolism

Proteins in all tissues are continually “turning over” (i.e., being degraded and replaced by new synthesis). This concept was introduced as early as 1939 when Schoenheimer et al. developed methods for tracking the fate of individual proteins and amino acids labeled with the “heavy” isotope of nitrogen (¹⁵N). When ¹⁵N-labeled tyrosine was administered to animals, only ~50% of the label was excreted as the parent form [11]. What happened to the remainder? It was found that the unexcreted amino acids were incorporated into body proteins or converted to other molecules. The magnitude of the dynamic processes of protein synthesis and protein degradation is not small. Estimates of protein turnover in adults indicate they degrade and resynthesize roughly 3–5% of body proteins daily and this occurs at measured rates of 3.5 to 4.5 g protein/kg/day [12]. This rate of protein metabolism is equivalent to a breaking down and rebuilding 1 to 1.5 kg of muscle/day (assuming that 20% of muscle weight is protein). From this perspective, it is obvious that the processes of protein breakdown must be highly selective because a degraded protein is irreversibly lost, terminating its actions. The selectivity of protein breakdown is not achieved by a method in which each protein is degraded by its specific protease. Instead, it appears that different conditions or stimuli result in activation of specific proteases to eliminate the substrate protein. As will be detailed, the principal protease in all cells is the ubiquitin-proteasome system (UPS). It is activated by different stimuli and it degrades a large variety of individual proteins or sets of proteins.

In response to CKD, there is an imbalance between protein synthesis and degradation resulting in net loss of protein stores, including that in the major store of protein in the body, skeletal muscle. This loss of protein stores contributes to the excessive frequency of morbidity and mortality in patients with CKD. For example, epidemiologic and clinical reports document that muscle wasting increases the risk of morbidity and mortality in CKD as it does in other catabolic conditions including heart failure, cancer and aging [13–15]. These catabolic conditions cause a specific loss of the contractile proteins that comprise about {2/3} of the protein in muscle and loss of these proteins is largely responsible for the disability of patients who experience muscle wasting [16]. Unfortunately, the muscle wasting advances as does the severity of CKD and can accelerate after the initiation of dialysis therapy. Cross-sectional studies have shown the prevalence of muscle wasting is between 40–70% in patients with end-stage renal disease (ESRD); the variability in these studies largely depends on which methods are used to identify an abnormality in protein stores [17]. Loss of protein stores and especially, those in skeletal muscle results in increasing dependency, a low quality of life with a sedentary, inactive lifestyle which jeopardizes the cardiovascular health of CKD patients [18]. Besides the body weight loss from a decrease in muscle mass, a progressive loss of protein stores includes proteins that regulate metabolism and cellular renewal, further jeopardizing health. Unfortunately, muscle wasting of patients with CKD is often underappreciated and can be insidious and slowly progressive in some patients.

Defining Muscle Wasting

A major problem in assigning cause–effect relationships for the muscle wasting present in CKD (or other catabolic conditions) is the lack of consensus surrounding definitions of muscle wasting. In large part, the confusion arises because of difficulties encountered in measuring protein stores reliably. In 2008, the International Society of Renal Nutrition and Metabolism proposed that low values of serum albumin, prealbumin and cholesterol plus abnormalities in body weight and anthropometry could identify patients with CKD who have lost protein stores [19]. They also suggested a new descriptive term, protein-energy wasting or PEW, as a method of classifying such patients [19]. The new term was believed to be needed to avoid confusion associated when malnutrition is used as a diagnosis. Specifically, CKD patients with a low serum albumin are frequently categorized as being malnourished but this diagnosis is incorrect since malnutrition is defined as abnormalities due to an inadequate diet or an unbalanced one. As pointed out earlier, if malnutrition was the cause of a low serum albumin and loss of protein stores, then both abnormalities should be corrected by simply changing the diet. Unfortunately, changing the diet rarely reverses the loss of protein stores in patients with CKD. Other popular diagnoses of lost protein stores in CKD patients were discarded because they were imprecise. For example, sarcopenia was discarded because it generally describes the loss of muscle mass associated with aging while cachexia was discarded because it implies a more severe state of protein depletion. A report from another Consensus Conference concluded that the term, cachexia, should be reserved for patients suffering from a complex metabolic syndrome initiated by illnesses or conditions that cause loss of muscle with or without loss of fat mass [20]. Specifically, it was recommended that a diagnosis of cachexia should be based on a 5% loss of edema-free body weight within 12 months and that there should be anthropometric evidence of muscle wasting plus evidence of inflammation and hypoalbuminemia. These characteristics would generally apply only to patients with CKD that is complicated by other illnesses.

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Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Chapter 1. The Influence of Kidney Disease on Protein and Amino Acid Metabolism
• Chapter 2. Carbohydrate Metabolism in Kidney Disease and Kidney Failure
• Chapter 3. Altered Lipid Metabolism and Serum Lipids in Kidney Disease and Kidney Failure
• Chapter 4. Uremic Toxicity
• Chapter 5. Inflammation in Chronic Kidney Disease
• Chapter 6. Catalytic (Labile) Iron in Kidney Disease
• Chapter 7. Carbonyl Stress in Uremia
• Chapter 8. Effect of Acidemia and Alkalemia on Nutrition and Metabolism
• Chapter 9. Prevention and Management of Cardiovascular Disease in Kidney Disease and Kidney Failure
• Chapter 10. Assessment of Protein and Energy Nutritional Status
• Chapter 11. Causes of Protein-Energy Wasting in Chronic Kidney Disease
• Chapter 12. Protein-Energy Wasting as a Risk Factor of Morbidity and Mortality in Chronic Kidney Disease
• Chapter 13. Effect of Nutritional Status and Changes in Protein Intake on Renal Function
• Chapter 14. Low Protein, Amino Acid and Ketoacid Diets to Slow the Progression of Chronic Kidney Disease and Improve Metabolic Control of Uremia
• Chapter 15. Reducing Tryptophan Metabolites to Reduce Progression in Chronic Kidney Failure
• Chapter 16. Altering Serum Lipids to Reduce Progression of Chronic Kidney Disease
• Chapter 17. Disorders of Phosphorus Homeostasis: Emerging Targets for Slowing Progression of Chronic Kidney Disease
• Chapter 18. Alkalinization to Retard Progression of Chronic Kidney Failure
• Chapter 19. Calcium, Phosphate, PTH, Vitamin D and FGF-23 in Chronic Kidney Disease
• Chapter 20. Phosphate Metabolism and Fibroblast Growth Factor 23 in Chronic Kidney Disease
• Chapter 21. Vitamin D in Kidney Disease
• Chapter 22. Nutritional Management of Water, Sodium, Potassium, Chloride, and Magnesium in Kidney Disease and Kidney Failure
• Chapter 23. Trace Elements, Toxic Metals, and Metalloids in Kidney Disease
• Chapter 24. Vitamin Metabolism and Requirements in Renal Disease and Renal Failure
• Chapter 25. Nutrition and Anemia in End-stage Renal Disease
• Chapter 26. Nutritional and Non-nutritional Management of the Nephrotic Syndrome
• Chapter 27. Nutrition and Blood Pressure
• Chapter 28. Effect of Obesity and the Metabolic Syndrome on Incident Kidney Disease and the Progression to Chronic Kidney Failure
• Chapter 29. Nutritional and Metabolic Management of Obesity and the Metabolic Syndrome in the Patient with Chronic Kidney Disease
• Chapter 30. Bariatric Surgery and Renal Disease
• Chapter 31. Nutritional and Metabolic Management of the Diabetic Patient with Chronic Kidney Disease and Chronic Renal Failure
• Chapter 32. Nutritional Management of Maintenance Hemodialysis Patients
• Chapter 33. Nutritional Management of End-Stage Renal Disease Patients Treated with Peritoneal Dialysis
• Chapter 34. Nutritional Management of Kidney Transplant Recipients
• Chapter 35. Nutritional Management of the Child with Kidney Disease
• Chapter 36. Nutritional Management of Acute Kidney Injury
• Chapter 37. Nutritional Management of Patients Treated with Continuous Renal Replacement Therapy
• Chapter 38. Anorexia and Appetite Stimulants in Chronic Kidney Disease
• Chapter 39. Oral and Enteral Supplements in Kidney Disease and Kidney Failure
• Chapter 40. Intradialytic Parenteral Nutrition, Intraperitoneal Nutrition and Nutritional Hemodialysis
• Chapter 41. Therapeutic Use of Growth Factors in Renal Disease
• Chapter 42. Nutritional Prevention and Treatment of Kidney Stones
• Chapter 43. Herbal Supplements in Patients with Kidney Disease
• Chapter 44. Drug–Nutrient Interactions in Renal Failure
• Chapter 45. Exercise Training for Individuals with Advanced Chronic Kidney Disease
• Chapter 46. Motivating the Kidney Disease Patient to Nutrition Adherence and Other Healthy Lifestyle Activities
• Color Plates
• Index