Nutritional Considerations in Kidney Disease: Core Curriculum 2010

Abstract

Nutritional considerations form an integral part in the care of a patient with kidney disease because of the kidney's central role in dietary metabolism. Not only can dietary manipulations ameliorate the signs and symptoms of kidney disease, but they also form an important adjunct of therapy regardless of the degree of decrease in kidney function. Whether the patient has chronic kidney disease (CKD) not yet requiring dialysis therapy, is undergoing renal replacement therapy, or has received a kidney transplant, timely and appropriate nutritional intervention can optimize patient care and outcomes. Last, nutritional markers, such as serum albumin, are highly predictive of morbidity and mortality and further emphasize the importance of nutritional concerns in the management of patients with kidney disease. •Chemical substance in food that serves as a metabolic fuel, a substrate for tissue growth or maintenance, or regulates normal cellular and metabolic processes•Indispensable nutrients are essential •Organic compounds that serve as sources of fuels for energy requirements∘Carbohydrates∘Fats∘Proteins•Vitamins∘Organic compounds, necessary in small amounts for normal growth, maintenance of health, and reproduction•Minerals∘Macroinorganic elements (eg, sodium, chlorine, calcium, magnesium, phosphorus)•Water •Amount considered sufficient for the maintenance of health in nearly all adults•Recommendations are concerned with health maintenance and are not intended to be sufficient for therapeutic purposes •Amounts considered optimal for promotion of health•Amounts vary for individuals of different risk and may be intended for therapeutic purposes in those with certain diseases •Dietary factors∘Chemical form of nutrient∘Energy intake∘Food processing and preparation∘Effect of other dietary constituents•Host factors∘Age∘Sex∘Genetic makeup∘Pathologic states »King J, Appel L, Bronner Y, et al. The Report of the Dietary Guidelines Advisory Committee on Dietary Guidelines for Americans, 2005. Washington DC: US Department of Health and Human Services; 2006.»Food and Nutrition Board of the Institute of Medicine. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington DC: US Institute of Medicine; 2006.»Lichtenstein AH, Appel LJ, Brands M, et al; American Heart Association Nutrition Committee. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114(1):82-96.»National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. Am J Kidney Dis. 2001;37(1 suppl 2):S66-70. •Healthy patients with CKD and transplant recipients may have normal or slightly decreased basal energy requirements•Caloric intake should be based on energy needs•Inflammatory diseases and dialysis increase basal energy expenditure•Dietary energy intake of about 30-35 kcal/kg/d is more likely to maintain or increase body mass, maintain neutral or positive nitrogen balance, and decrease urinary nitrogen appearance for CKD and dialysis patients•Sedentary individuals older than 60 years may be prescribed 30 kcal/kg/d, as well as patients who are obese with edema-free body weight >120% of desirable body weight for CKD and dialysis patients »Kamimura MA, Draibe SA, Avesani CM, Canziani ME, Colugnati FA, Cuppari L. Resting energy expenditure and its determinants in hemodialysis patients. Eur J Clin Nutr. 2007;61(3):362-367.»Mafra D, Deleaval P, Teta D, et al. New measurements of energy expenditure and physical activity in chronic kidney disease. J Ren Nutr. 2009;19(1):16-19.»Mak RH, Cheung W. Energy homeostasis and cachexia in chronic kidney disease. Pediatr Nephrol. 2006;21(12):1807-1814. In patients with CKD, patients with end-stage renal disease (ESRD), and transplant patients, metabolism is impaired, leading to glucose intolerance, insulin resistance, and impaired insulin secretion. •Skeletal muscle is the major site for decreased sensitivity to insulin action•Other defects in glucose metabolism exist at steps in the glycolytic pathway before the production of glyceraldehyde-3-phosphate•Hepatic glucose production and suppression of its production by insulin occur normally•A postreceptor defect (impairment of IRS-1 [insulin receptor substrate 1]) is responsible for resistance to the peripheral action of insulin in uremia∘Occurs early in the course of CKD and is observed in most patients with advanced CKD (stages 4 and 5) and those treated with hemodialysis∘Defect is markedly improved with hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or dietary protein restriction, suggesting that a dialyzable compound may be involved•Glucocorticoids (eg, prednisone), obesity, and calcineurin inhibitors further exacerbate insulin resistance •In response to hyperglycemia, blood insulin levels may be decreased, normal, or increased•Both the initial and late phases of insulin secretion are impaired in CKD•Response to l-leucine and potassium (insulin secretagogues) is impaired•Excess parathyroid hormone (PTH) inhibits insulin secretion independent of CKD∘Caused by an increase in basal calcium levels in pancreatic islets, impairing activities of the calcium-transporting adenosine triphosphatase (Ca2+-ATPase) and adenosine triphosphatase sodium-potassium pump (Na+-K+-ATPase)∘Insulin secretion is markedly improved in children with ESRD after normalization of blood PTH levels by treatment with vitamin D•The metabolic clearance rate of insulin also varies because insulin is metabolized and cleared by the kidney∘Daily renal clearance of insulin (6-8 units) is impaired when glomerular filtration rate (GFR) decreases to <40 mL/min, markedly prolonging the half-life∘Fasting blood glucose levels are normal, but spontaneous hypoglycemia occurs∘Fasting and postprandial hyperinsulinemia▪Proinsulin, C-peptide, glucagon, and growth hormone levels also are increased∘The metabolic clearance rate of insulin is improved with dialysis, most likely by increasing its degradation in peripheral tissues •A diet moderate to rich (depending on caloric needs) in complex carbohydrates is advised∘Lower glycemic index carbohydrates (complex carbohydrates) are preferred carbohydrate sources to prevent hyperglycemia due to insulin resistance∘The high phosphorus and/or potassium content of many complex carbohydrates (legumes, whole grains, fruit) creates difficulties in those with stages 3-5 CKD and ESRD∘Other strategies to control phosphorus and potassium levels may allow greater consumption of complex carbohydrates•Very low-carbohydrate diets may be tolerated poorly because of the long insulin half-life »Adrouge HJ. Glucose homeostasis and the kidney. Kidney Int. 1992;42:1266-1271.»DeFronzo RA, Alvestrand A, Smith D, Hendler R. Insulin resistance in uremia. J Clin Invest. 1981;67:563-568.»DeFronzo RA, Andres R, Edgar P, Walker WG. Carbohydrate metabolism in uremia: a review. Medicine (Baltimore). 1973:52;469-481.»Mak RH. Impact of end-stage renal disease and dialysis on glycemic control. Semin Dial. 2000;13:4-8.»Procopio M, Borretta G. Derangement of glucose metabolism in hyperparathyroidism. J Endocrinol Invest. 2003;26:1136-1142.»Rigalleau V, Gin H. Carbohydrate metabolism in uraemia. Curr Opin Clin Nutr Metab Care. 2005;8:463-469.»Wahba IM, Mak RH. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol. 2007;2(3):550-562.»Zanetti M, Barazzoni R, Guarnieri G. Inflammation and insulin resistance in uremia. J Ren Nutr. 2008;18:70-75. Lipid abnormalities are common in kidney disease, including CKD, nephrotic syndrome, and dialysis dependence. •Two causes of moderate plasma hypertriglyceridemia∘Augmented synthesis by intestine or liver∘Impaired triglyceride removal from plasma•Hepatic triglyceride lipase and lipoprotein lipase (LPL) activities are decreased∘Gemfibrozil, which activates both hepatic triglyceride lipase and LPL, can normalize the hypertriglyceridemia of CKD∘Metabolism of newly secreted chylomicrons and very low-density lipoprotein (VLDL) particles is delayed by diminished LPL activity∘Clearance of partially metabolized lipoproteins and chylomicron remnants is delayed by decreased hepatic triglyceride lipase activity•Plasma apolipoprotein profiles are highly abnormal∘Apolipoprotein AI (Apo-AI), Apo-AII, and Apo-E concentrations are decreased∘Apo-B level is slightly increased∘Apo-CIII levels are significantly increased, whereas Apo-CI and Apo-CII are slightly increased∘Apo-CIII ratio is abnormally low▪Equal to ratio of Apo-CIII in heparin-treated plasma supernatant to that present in precipitate▪Correlates with the efficacy of processes responsible for the degradation of triglyceride-rich particles •Dyslipidemia is present in 70%-100% of patients∘Most often appears as combined hyperlipidemia, with increased total serum cholesterol, low-density lipoprotein (LDL) cholesterol, VLDL cholesterol, and intermediate-density lipoprotein (IDL) cholesterol, accompanied by increased serum triglyceride levels∘Types of hyperlipidemia (see Box 1 for characteristics)▪Type IIa is present in 33%▪Type IIb is present in 50%▪Type IV (hypertriglyceridemia) is present in 4%Box 1Types of DyslipidemiaType IIa↔ Triglycerides↑↑↑ Cholesterol↑ LDL cholesterol↑ HDL cholesterolType IIb↑ VLDL cholesterol↑↑ Triglycerides↑↑ or ↑↑↑ Cholesterol↑ LDL cholesterol↑↑ HDL cholesterolType IV↑ VLDL cholesterol↑↑ Triglycerides↓ or ↑ Cholesterol↓ LDL cholesterol↑↑ HDL cholesterolAbbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.∘High-density lipoprotein (HDL) cholesterol levels can be low, normal, or high∘Increased hepatic synthesis and decreased lipid and lipoprotein catabolism contribute to the hyperlipidemia, with various mechanisms proposed•Changes in plasma apolipoprotein concentrations parallel changes in lipoproteins∘Apo-B and Apo-E levels are increased∘Apo-AI reflects HDL cholesterol levels∘Apo-CI, Apo-CII, and Apo-CIII levels are increased, but there is no change in Apo-CII:Apo-CIII ratio∘Levels of lipoprotein(a) (Lp[a]), a powerful atherosclerotic risk factor, are increased Type IIa ↔ Triglycerides ↑↑↑ Cholesterol ↑ LDL cholesterol ↑ HDL cholesterol Type IIb ↑ VLDL cholesterol ↑↑ Triglycerides ↑↑ or ↑↑↑ Cholesterol ↑ LDL cholesterol ↑↑ HDL cholesterol Type IV ↑ VLDL cholesterol ↑↑ Triglycerides ↓ or ↑ Cholesterol ↓ LDL cholesterol ↑↑ HDL cholesterol Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein. •Typical pattern is hypertriglyceridemia in combination with low HDL cholesterol level •Lipoprotein abnormalities similar to those found in hemodialysis patients•However, plasma cholesterol, triglyceride, LDL cholesterol, and Apo-B levels are higher because of:∘Loss of considerable amounts of protein into peritoneal dialysate (7-14 g/d)∘Excessive absorption of glucose (150-200 g/d) •Increased cholesterol and triglyceride levels•Type of dyslipidemia and prevalence vary considerably•Influencing factors∘Concomitant drug treatment for hypertension (β-blockers and diuretics) or immunosuppression∘Insulin resistance∘Obesity∘Transplant dysfunction •Diets to improve lipid abnormalities in patients with kidney diseases have not been well studied•Although lipid patterns represent a highly atherogenic condition, the degree to which diets may modify lipid levels or affect the risk of coronary heart disease is unknown•Lipid-lowering drugs have not been very effective in causing regression of coronary artery disease in patients with nephrotic syndrome, on hemodialysis or CAPD therapy, or after kidney transplant•Hypertriglyceridemia increases insulin resistance, with effects on carbohydrate and protein metabolism•There are few data for the relation of dyslipidemia to progression of kidney disease•Increased serum lipid levels parallel lipid deposits and lipoprotein components in human glomerular disease (focal segmental glomerulosclerosis [FSGS])•In patients with type 1 diabetic nephropathy, cholesterol levels are an independent risk factor for progression after blood pressure and glycemic control are considered •Bases for decision to modify lipid content∘Extrapolation from epidemiologic and clinical studies in nonrenal conditions∘Conventional individual assessment of the patient's lipid profile, risk profile, and prognosis•Treatment recommended for subsets of patients∘Established coronary artery disease and hyperlipidemia∘Diabetes with high risk of cardiovascular event∘Nephrotic syndrome or early-stage CKD∘High LDL cholesterol level (>160 mg/dL [>4.14 mmol/L])∘High serum triglyceride level (>100-500 mg/dL [>1.54-5.65 mmol/L])∘Marked hyperlipidemia in a young or middle-aged man facing decades of renal replacement therapy •Serum total cholesterol and triglyceride levels should be monitored every 3-6 months, and serum LDL and HDL cholesterol levels should be monitored annually•Body weight should be maintained near desirable weight in early CKD and transplant patients•In patients with significant comorbid conditions, stage 5 CKD, or ESRD, body weight goals are controversial because of the risk of protein-energy wasting (PEW; discussed later)∘Weight reduction should be avoided in patients with PEW∘Resistive exercise is still strongly recommended in these groups•In patients with nephrotic syndrome in early stages of CKD, stringent diet modification (eg, reduced meat and/or soy-based vegetarian diets with fish oil) significantly decreased total cholesterol, LDL cholesterol, and triglyceride levels and proteinuria∘Fat restriction and the quality of fats and proteins in manipulated diets may be important for correction of hypercholesterolemia and urinary protein loss•Strategies for lipid modification of the diet appropriate for the high-risk general population may be appropriate in all kidney patients unless the change in lipid sources adds nutritional difficulties that prevent adequate protein and calorie intake•Diets rich in polyunsaturated fatty acids of both vegetable origin (omega 6) and fish, nut, or vegetable origin (omega 3) have increased the removal of triglyceride-rich lipoprotein remnants and dramatically decreased postprandial lipoprotein levels in plasma of nonrenal patients•Exercise training may improve dyslipidemia and glucose tolerance•Avoiding excessive weight gain after kidney transplant appears to be important•Cholesterol- and triglyceride-lowering drugs have effects on serum lipid levels quantitatively similar in kidney patients and the healthy population »Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk for cardiovascular disease. Circulation. 2009;119:902-907.»Kasiske BL; K/DOQI Dyslipidemia Work Group. Clinical practice guidelines for managing dyslipidemias in kidney transplant patients [letter]. Am J Transplant. 2005 5:1576.»Kaysen GA. Lipid and lipoprotein metabolism in chronic kidney disease. J Ren Nutr. 2009;19(1):73-77.»Kronenberg F. Dyslipidemia and nephrotic syndrome: recent advances. J Ren Nutr. 2005;15(2):195-203.»Kwan BC, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol. 2007;18(4):1246-1261.»National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis. 2003;41(suppl 4):S1-93»Ritz E, Wanner C. Lipid abnormalities and cardiovascular risk in renal disease. J Am Soc Nephrol. 2008;19(6):1065-1070. CKD (especially ESRD) causes abnormal protein metabolism. •Stages 4 and 5 CKD may cause striking abnormalities in free amino acid concentrations in muscle and plasma∘Essential amino acid levels are lower in plasma secondary to augmented peripheral tissue metabolism∘Levels of plasma branched-chain amino acids (BCAAs; valine, leucine, and isoleucine, as well as threonine and tryptophan) are especially low▪Acidosis and glucocorticoids worsen these changes▪Plasma and muscle BCAA concentrations, depressed in patients with uremia, are corrected by supplementing the diet with sodium bicarbonate•Acidosis-stimulated muscle proteolysis and total-body leucine oxidation require glucocorticoids•Because leucine has an anabolic effect on muscle, low levels could drive muscle wasting•Histidine and serine become essential amino acids in patients with ESRD because of decreased synthesis•Lower ratio of tyrosine to phenylalanine is caused by depressed liver tyrosine hydroxylase activity•In patients with ESRD, losses of amino acids in dialysate decrease plasma levels •Altered by CKD and nutritional status•Nonurea nitrogen metabolism is the difference between total nitrogen excretion and urea nitrogen appearance and represents fecal and nonurea nitrogen appearance∘Urea excreted into the gut is degraded by bacterial urease to ammonia and carbon dioxide, which returns to the liver through the portal circulation▪This extrarenal clearance of nitrogen increases in CKD, but does not significantly decrease the quantity of retained waste products (most are simply converted to another form of nitrogen)▪The difference between urea production and that recycled by the gut is termed “urea nitrogen appearance,” which represents urea that appears in body water and urine∘Fecal nitrogen excretion does not increase significantly in patients with uremia unless there is compromise in gut or liver function•As urinary function decreases, renal ammonia production decreases, which decreases the proportion of urinary nitrogen presenting as ammonia •Dietary protein in excess of daily requirements is degraded to urea, other nitrogenous waste, acid, phosphate, and sulfate∘These waste products accumulate in patients with uremia, leading to muscle catabolism, bone loss, and vascular calcification∘Correction of acidosis slows loss of kidney function•Dietary protein restriction slows progression of CKD∘Protein or amino acid loads:▪Acutely alter renal hemodynamics▪Increase proteinuria∘Decreases acid, uric acid, and nitrogenous waste generation∘Clinical results of protein restriction vary due to primary diagnosis and variability in achieving goal protein intakes•In response to catabolic stimulus or inadequate protein or caloric intake, endogenous protein stores also are degraded∘Protein synthesis and protein catabolism are normal in patients with CKD unless a second process is present∘Inability to adapt to a low-protein diet may be due to inadequate caloric intake▪Anorexia is a common symptom of both uremia and comorbid conditions▪Caloric requirements are higher in patients with ESRD (up to 35-40 kcal/kg) due to an increased basal metabolic rate, which is driven by high sympathetic nervous system activity∘When calories are inadequate, dietary amino acids are used for energy, increasing the need for muscle stores to supplement visceral protein synthesis •Inflammation is a major catabolic stimulus∘Acute-phase reactants are made instead of albumin, and albumin catabolism increases∘Insulin resistance drives loss of muscle protein▪Glucocorticoids and inflammatory cytokines have major roles∘Inflammation often is caused by comorbid conditions rather than CKD▪Chronic comorbid conditions (diabetes mellitus, lupus erythematosus, heart failure, nephrotic syndrome, emphysema)▪Acute intercurrent illnesses•Altered hormonal milieu promotes catabolism by:∘Resistance to the anabolic hormones (insulin, growth hormone, insulin-like growth factor 1 [IGF-1])∘Increased levels of catabolic hormones (glucagon, PTH, corticosteroids)•Other catabolic stimuli∘Accumulation of toxic uremic metabolites∘Loss of the kidney's metabolic activity∘Metabolic acidosis▪Acidosis decreases amino acid levels▪Acidosis blocks insulin-stimulated muscle protein synthesis∘ESRD is always associated with protein catabolism▪Inflammation from the dialysis procedure▪Amino acid loss during dialysis •Neutral nitrogen balance can be achieved in patients with nondialysis CKD with a minimum of 0.6 g/kg/d of high-biological-value protein in stable nonacidotic patients when adequate calories are given∘High-biological-value protein contains a high fraction of the essential amino acids proportioned approximately according to daily dietary requirements for humans▪At least 0.35 g/kg/d should be high-biological-value protein▪Essential amino acids may be supplemented or administered as their ketoanalogues∘If achieved, such diets slow progression, decrease acid and phosphorus loads•Low-protein diets have been proved safe in individuals with strict monitoring of nutritional status∘Many individuals are unwilling or unable to comply with such diets or monitoring▪Diets higher in protein (0.75 g/kg/d) are recommended for such patients with predialysis CKD▪At least 0.35 g/kg/d should be high-biological-value protein•Patients with active comorbid conditions may not tolerate protein-restricted diets (see PEW section)∘Evidence of deterioration should lead to a diagnostic workup for comorbid conditions∘Dietary protein intake should be liberalized during acute illnesses•Patients with ESRD will not tolerate low-protein diets∘Recommended protein intakes▪1.0-1.2 g/kg/d (hemodialysis)▪1.2-1.4 g/kg/d (peritoneal dialysis)∘Higher protein and amino acid losses in peritoneal fluid account for the differences•Transplant patients on steroid therapy will not tolerate the lowest protein diets »Bernstein AM, Treyzon L, Li Z. Are high protein, vegetable-based diets safe for kidney function? A review of the literature. J Am Diet Assoc. 2007;107:644-650.»Franch HA, Mitch WE. Catabolism in uremia: the impact of metabolic acidosis. J Am Soc Nephrol. 1998;9(suppl 12):S78-81.»Franch HA, Mitch WE. Navigating between the Scylla and Charybdis of prescribing dietary protein for chronic kidney diseases. Annu Rev Nutr. 2009;29:341-364.»Ikizler TA. Nutrition, inflammation and chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17(2):162-167.»Kaysen GA, Dubin JA, Müller HG, Mitch WE, Rosales LM, Levin NW. Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients. Kidney Int. 2002;61(6):2240-2249.»Levey AS, Greene T, Beck GJ, et al. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD Study shown? Modification of Diet in Renal Disease Study Group. J Am Soc Nephrol. 1999;10(11):2426-2439.»Lim VS, Ikizler TA, Raj DS, Flanigan MJ. Does hemodialysis increase protein breakdown? Dissociation between whole-body amino acid turnover and regional muscle kinetics. J Am Soc Nephrol. 2005;16(4):862-868. •Intestinal absorption of riboflavin, folate, and vitamin D3 decreases with decreasing GFR•Patients with CKD, acute kidney injury (AKI), and ESRD may have a higher incidence of vitamin deficiencies∘1,25-Dihydroxycholecalciferol production is decreased∘Vitamin intake is decreased because of anorexia and decreased food intake▪The prescribed diet frequently contains less than the recommended daily allowances for certain water-soluble vitamins•Kidney injury alters the absorption, metabolism, or activity of some vitamins∘Riboflavin, folate, and vitamin D3 absorption is impaired∘Folate and pyridoxine metabolism is impaired•Certain medicines may interfere with the intestinal absorption, metabolism, or actions of vitamins•Nutritional requirements for most vitamins are not well defined in patients with CKD, but there is some evidence that daily supplements of the following vitamins will prevent or correct vitamin deficiencies:∘Pyridoxine hydrochloride, 5 mg∘Folic acid, 1 mg∘Recommended daily allowances for healthy individuals for other water-soluble vitamins▪Vitamin C, 60 mg; higher doses have been associated with increased plasma oxalate levels▪Supplemental vitamin A is not recommended▪Vitamin K often is not needed▪Vitamin D should be supplemented to a plasma level >30 pg/mL•These deficiencies are severe after institution of dialysis therapy because of the loss of water-soluble vitamins in dialysate on a thrice-weekly regimen∘Replacement is similar to CKD, except 75-90 mg/d of vitamin C, 10-50 mg/d of pyridoxine, and 1-5 mg/d of folate should be prescribed »Falkenhain ME, Hartman JA, Hebert L. Nutritional management of water, sodium, potassium, chloride, and magnesium in renal disease and renal failure. In: Kopple J, Massry S, eds. Kopple and Massry's Nutritional Management of Renal Diseases. New York, NY: Lippincott, William & Williams; 2004:287-299.»Fouque D, Vennegoor M, Ter Wee P, et al. EBPG Guideline on Nutrition. Nephrol Dial Transplant. 2007;22(suppl 2):ii45-87.»Kalantar-Zadeh K, Kopple JD. Trace elements and vitamins in maintenance dialysis patients. Adv Ren Replace Ther. 2003;10:170-182.»Kalantar-Zadeh K, Regidor DL, Kovesdy CP, et al. Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis. Circulation. 2009;119(5):671-679.»KDIGO CKD-MBD Work Group. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1-130.»Thijssen S, Kitzler TM, Levin NW. Salt: its role in chronic kidney disease. J Ren Nutr. 2008;18(1):18-26.»Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin Dial. 2007;20:295-301. •PEW occurs when mechanisms to compensate for decreased protein intake fail (see previous Protein Metabolism section)∘PEW occurs frequently in patients with stages 4 and 5 CKD and established hemodialysis or peritoneal dialysis patients∘Dietary protein and energy intake and the parameters of nutritional status (including serum albumin, transferrin, body weight, midarm muscle circumference, and percentage of body fat) decrease as GFR decreases toward 10 mL/min/1.73 m2 (0.167 mL/s/1.73 m2) •Nutritional status of patients undergoing maintenance hemodialysis or peritoneal dialysis is a powerful predictor of morbidity and mortality∘Serum albumin, weight, muscle mass, and changes in body weight are associated with morbidity and mortality∘Comorbid conditions often account for both the PEW and increased mortality∘Individuals with lower muscle mass may be less likely to survive acute intercurrent illnesses∘The term “reverse epidemiology” describes lower mortality with higher body weight, cholesterol level, and other traditional cardiac risk factors that is believed to be caused by PEW •Treatment of PEW depends on reversing the acute illness, providing adequate protein and calories, and muscle loading to rebuild muscle mass∘In patients with CKD, dietary protein intake should be liberalized∘Reduction of inflammation portends a good prognosis∘Dietary supplements are helpful in restoring albumin levels in patients with low spontaneous protein and/or calorie intake (Table 1)▪Intradialytic parenteral nutrition appears effective, but not superior to oral feedingTable 1Liquid Protein SupplementsProductAmountCaloriesProtein (g)Calcium (mg)Potassium (mg)Phosphorus (mg)Sodium (mg)Boost8 fl oz24010330400310130Boost High Protein8 fl oz24015330380310170Boost Plus8 fl oz36014330380310170Boost Diabetic237 mL25013.8276260220260Ensure8 fl oz2508.8300370300200Ensure High Protein8 fl oz23012300500250290Ensure Plus8 fl oz35013300500300240Glucerna8 fl oz2379.9170370170220Nepro Carb SteadyaIndicated for dialysis patients.8 fl oz42519.1250250165250Novasource RenalaIndicated for dialysis patients.8 fl oz47517.4308192154210Promote8 fl oz23714.8285470285240Suplena Carb Steady8 fl oz42510.6250265165185Resources Shake Plus8 fl oz48015350250350200Nutren Renal8 fl oz50017.5350314175185Re/Gen HP/HCaIndicated for dialysis patients.4 fl oz2501015254590Note: Boost, Novasource Renal, Resources Shake Plus, and Nutren Renal products are manufactured by Nestle (www.nestle-nutrition.com); Ensure, Glucerna, Nepro Carbo Steady, Promote, Suplena Carb Steady, by Abbott Laboratories (www.abbott.com); Re/Gen HP/HC by Nutra/Balance Products (www.nutra-balance-products.com).a Indicated for dialysis patients. Open table in a new tab ∘Dietary supplements are not effective in restoring muscle mass without muscle loading▪Feeding can increase muscle protein synthesis, but this is matched by increased breakdown in individuals at rest∘The role of spontaneous versus prescribed exercise has not been determined▪Exercise programs have been recommended in analogy to exercise use in patients with cancer, heart failure, and lung disease muscle wasting▪No protocol has been successfully developed specifically for kidney patients∘Anabolic agents (eg, growth hormone, IGF-1, anabolic steroids) and appetite stimulants (eg, progesterones) are under active investigation for PEW▪Many anabolic agents have had successful small-scale trials▪Optimal regimens have not been established▪The role of carnitine, used in the transport of fatty acids, and its supplementation has been debated Note: Boost, Novasource Renal, Resources Shake Plus, and Nutren Renal products are manufactured by Nestle (www.nestle-nutrition.com); Ensure, Glucerna, Nepro Carbo Steady, Promote, Suplena Carb Steady, by Abbott Laboratories (www.abbott.com); Re/Gen HP/HC by Nutra/Balance Products (www.nutra-balance-products.com). »Bailey JL, Franch HA. Getting to the meat of the matter: beyond protein supplementation in maintenance dialysis. Semin Dial. 2009;22:512-518.»Cano NJ, Fouque D, Roth H, et al; French Study Group for Nutrition in Dialysis. Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomized study. J Am Soc Nephrol. 2007;18(9):2583-2591.»Dong J, Ikizler TA. New insights into the role of anabolic interventions in dialysis patients with protein energy wasting. Curr Opin Nephrol Hypertens. 2009;