Nutrition and Kidney Disease

Amino Acid Metabolism

CKD patients have well-defined abnormalities in their plasma and, to a lesser extent, in their muscle amino acid profiles. Commonly, essential amino acid concentrations are low and nonessential amino acid concentrations high. The etiology of this abnormal profile is complex. The progressive loss of kidney tissue, where metabolism of several amino acids takes place, is an important factor. Specifically, glycine and phenylalanine concentrations are elevated, and serine, tyrosine, and histidine concentrations are decreased. Plasma and muscle concentrations of branched-chain amino acids (valine, leucine, and isoleucine) are reduced in CKD patients, especially in patients treated with maintenance dialysis. In contrast, plasma citrulline, cystine, aspartate, methionine, and both 1- and 3-methylhistidine levels are increased. Although inadequate dietary intake is a possible factor in abnormal essential amino acid profiles, certain abnormalities occur even in the presence of adequate dietary nutrient intake indicating that the uremic milieu has an additional effect. Indeed, it has been suggested that the metabolic acidosis commonly seen in uremic patients plays an important role in increased oxidation of branched-chain amino acids.

Protein Intake in Nondialysis CKD Patients

In general, the minimal daily protein requirement is one that maintains a neutral nitrogen balance and prevents protein wasting; this has been estimated to be a daily dietary protein intake of about 0.8 g/kg. One of the most significant symptoms in advanced CKD is a decrease in appetite. Several studies have indicated that CKD patients spontaneously restrict their dietary protein intake, with levels often less than 0.6 g/kg/day among those with CKD stage 5, suggesting that anorexia predisposes CKD patients to PEW. Accumulation of uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and fibroblast growth factor 23 (FGF-23) may not be the sole cause of decreased dietary nutrient intake. Table 52.1 depicts factors that can cause decreased nutrient intake as well as other potential mechanisms of PEW in CKD patients. Individuals with CKD and coexisting diabetes mellitus are more prone to nutritional abnormalities because of additional dietary restrictions; gastrointestinal symptoms common in diabetes such as gastroparesis, nausea, and vomiting; bacterial overgrowth in the gut; and pancreatic insufficiency. Depression is common in CKD and is also associated with anorexia. CKD patients often are prescribed a large number of medications, particularly sedatives, phosphate binders, and iron supplements, all of which may have gastrointestinal complications. Finally, socioeconomic status, lack of mobility, dependency, and older age may all predispose to decreased dietary protein intake.

Protein Restriction in Nondialysis CKD

Dietary protein restriction, with or without supplementation of ketoanalogues of certain amino acids, has long been considered an attractive intervention to both slow the progression of kidney disease and delay initiation of maintenance dialysis. This is based on earlier studies indicating that excessive dietary protein intake causes vasodilation in the afferent arterioles, resulting in hyperfiltration, which, over time, leads to progression of kidney disease, especially in high-risk populations such as those with coexisting diabetes mellitus and hypertension. Reduced protein intake, however, leads to vasoconstriction in the afferent arterioles and lowers intraglomerular pressure. As suggested by a number of meta-analyses, this dietary protein restriction effect is real, albeit relatively small in the context of progressive kidney disease (0.5 mL/min/year benefit). Notably, patients with certain kidney diseases such as polycystic kidney disease do not seem to benefit from low-protein diets.

Several smaller studies suggest that the favorable effects of dietary protein restriction extend beyond slowing CKD progression. These include amelioration of metabolic acidosis, improvements in the lipid profile and insulin resistance, antioxidant effects, and decreasing dietary phosphorus load. The optimal range of dietary protein restriction to exert the most beneficial outcome is not established, and the applicability of dietary protein restriction is limited by adherence.

In addition to protein restriction alone, a number of studies have also examined the effects of keto acid– or amino acid–­supplemented low-protein diets (LPDs) or very-low-protein diets (VLPDs) on certain metabolic and kidney outcome parameters. Since the supplemental keto acids are primarily given to substitute for dietary protein intake, most studies evaluated VLPDs. Accordingly, several meta-analyses indicate that VLPD diets supplemented with keto acids delay the initiation of maintenance dialysis along with a significant decrease in urea production and potential beneficial effects on insulin resistance and oxidative stress in humans.

An important consideration regarding dietary protein restriction in CKD is the potential to adversely affect nutritional status. These concerns are mostly ameliorated by well-designed diets planned by skilled dietitians and followed by motivated and adherent patients, and multiple studies have showed these diets are effective and do not have harmful effects on the nutritional condition. Long-term follow-up of several relatively large cohorts of CKD patients who received 0.47 g/kg/day protein with keto acid supplementation showed no detrimental effect on clinical outcomes. Accordingly, one can conclude that prescribing LPD or VLPD with keto acid or amino acid supplementation with adequate caloric intake and close supervision does not lead to overt PEW.

There are very limited data regarding the optimal level of dietary protein intake in patients with a kidney transplant. In general, these patients should also be considered as having CKD, and the same strategies for dietary protein intake and prescription should be applied. Table 52.2 describes current recommendations for dietary protein and energy intake for patients by CKD stage.