Abstract
As chronic kidney disease (CKD) progresses, the requirements and utilization of different nutrients change significantly. Protein energy wasting (PEW), defined as a state of decreased body stores of protein and energy fuels, is common in individuals with CKD, and has multifactorial causes. Changes in nutritional needs and utilization ultimately place kidney disease patients at high risk for nutritional abnormalities. Understanding the applicable nutritional principles and the available methods for improving nutritional status of these patients is essential. National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease and Nutrition in Chronic Kidney Disease provide in-depth information regarding these principles.
Keywords
Chronic kidney disease, Dialysis, Nutrition, Protein energy wasting, Phosphate, Sodium, Malnutrition
As chronic kidney disease (CKD) progresses, the requirements and utilization of different nutrients change significantly. Protein energy wasting (PEW), defined as a state of decreased body stores of protein and energy fuels, is common in individuals with CKD and has multifactorial causes. Changes in nutritional needs and utilization ultimately place kidney disease patients at high risk for nutritional abnormalities. Understanding the applicable nutritional principles and the available methods for improving nutritional status of these patients is essential. National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease and Nutrition in Chronic Kidney Disease provide in-depth information regarding these principles.
Nutrient Metabolism in Kidney Disease
Protein Metabolism and Requirements
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 multifactorial. 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 protein intake of approximately 0.6 g/kg in healthy individuals, with a safe level of protein intake equivalent to the minimal requirement plus 2 standard deviations, or approximately 0.75 g/kg per day. 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 per day among those with CKD stage 5, suggesting that anorexia predisposes CKD patients to malnutrition. Accumulation of uremic toxins may not be the sole cause of decreased dietary nutrient intake. Table 53.1 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; and bacterial overgrowth in the gut and pancreatic insufficiency. Depression, which is common in CKD, 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, and older age may all predispose to decreased dietary protein intake.
| Increased Protein and Energy Requirements |
|
| Decreased Protein and Calorie Intake |
|
| Increased Catabolism/Decreased Anabolism |
|
Protein Restriction in Nondialysis CKD Patients
Dietary protein restriction, with or without supplementation of ketoanalogues of certain amino acids, has long been considered an attractive intervention to slow the progression of kidney disease. This is based on earlier studies indicating that excessive dietary protein intake causes hyperfiltration leading to progression of kidney disease, especially in high-risk populations such as individuals with coexisting diabetes mellitus and hypertension. 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 per year benefit). Several smaller studies suggest that the favorable effects of dietary protein restriction extend beyond slowing the progression. These include amelioration of metabolic acidosis 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 compliance.
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. Several studies indicate that protein-restricted diets supplemented with keto acids and amino acids result in a significant decrease in urea production and a beneficial effect 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 have been mostly ameliorated by a number of studies showing that well-designed diets planned by skilled dietitians and followed by motivated and adherent patients 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 per day protein with ketoacid supplementation showed no detrimental effect on clinical outcomes. Accordingly, one can conclude that prescribing LPD or VLPD with or without keto acid or amino acid supplementation with adequate caloric intake and close supervision does not seem to lead to 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 53.2 depicts the most current recommendations for dietary protein and energy intake for patients with different stages of CKD.
| Protein | Energy | Phosphorus | Sodium | |
|---|---|---|---|---|
| Chronic Kidney Disease | ||||
| Stages 1–3 | No restriction | No restriction | 600–800 mg/day | <2 g/day a |
| Stages 4–5 | 0.60–0.75 g/kg/day b | 30–35 kcal/kg/day c | 600–800 mg/day d | <2 g/day |
| Dialysis | ||||
| Hemodialysis | >1.2 g/kg/day | 30–35 kcal/kg/day c | 600–800 mg/day d | <2 g/day |
| Peritoneal dialysis | >1.3 g/kg/day | 30–35 kcal/kg/day c | 600–800 mg/day d | <2 g/day |
| Acute Kidney Injury | ||||
| No dialysis | 1.0–1.2 g/kg IBW/d | 30–35 kcal/kg/day | 600–800 mg/day d | <2 g/day |
| Dialysis | 1.2–1.4 g/kg IBW/d | 30–35 kcal/kg/day | 600–800 mg/day d,e | <2 g/day |
b With close supervision and frequent dietary counseling.
c 30 kcal/kg/day for individuals 60 years and older.
Maintenance Dialysis Patients
Once CKD patients are initiated on maintenance dialysis, dietary restrictions are used to prevent hyperphosphatemia, hyperkalemia, or metabolic acidosis; however, these restrictions could predispose dialysis patients to an increased risk of PEW, primarily because of the increased metabolic stress associated with dialysis therapies. Nutrient losses through hemodialysis or peritoneal membranes, loss of residual kidney function due to long-term dialysis treatment, and increased inflammation due to indwelling catheters, bioincompatible hemodialysis membranes, and peritoneal dialysis (PD) solutions all may lead to an overly catabolic milieu and increase the minimal amount of nutrient intake needed to maintain a neutral nitrogen balance (see Table 53.2 ). In patients who cannot compensate for this increased need, a state of semistarvation ensues, resulting in the development or worsening of PEW. Although the current targets for acceptable dialysis dose should be adequate to prevent development of PEW in patients undergoing either hemodialysis or PD, there are limited data suggesting that a substantial increase in dose of dialysis could result in improvement in overall nutrition status in maintenance dialysis patients.
Chronic Inflammation
Systemic inflammation is one of the major contributors to PEW in patients with CKD ( Fig. 53.1 ). Increased levels of proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor–α (TNF-α) play a crucial role in the exaggerated protein and energy catabolism present in individuals with CKD. Proinflammatory cytokines play integral roles in protein breakdown, resulting in muscle atrophy in chronic disease states such as advanced CKD. Recent data in maintenance hemodialysis patients clearly indicate exponentially increased protein catabolism, especially in the skeletal muscle compartment, in the setting of exaggerated systemic inflammation. In addition to increasing protein breakdown, chronic inflammation is associated with reduced physical activity and impairment in both insulin and growth hormone actions; it may also contribute to anorexia due to central effects. Small randomized studies suggest that certain antiinflammatory interventions such as IL1 receptor blockers , pentoxifylline, and fish oil could improve protein catabolism in maintenance dialysis patients.
