Prevention and treatment
Managing the nutritional concerns of maintenance dialysis patients includes a comprehensive combination of preventive maneuvers to diminish protein and energy depletion (Table 1). Standard therapies for maintenance dialysis patients with muscle wasting include provision of adequate dialysis, treatment of metabolic acidosis, adjustments of dietary factors, and treatment of infections.
Nutritional supplementation. The susceptibility of maintenance dialysis patients to PEW resulting from decreased protein and energy intake can be ameliorated by increasing nutrient intake through dietary supplements, especially during hemodialysis. Nutritional supplementation should be delivered by the oral route if at all possible; otherwise, parenteral nutritional supplements can be administered.
In a meta-analysis that included 18 studies (five randomized controlled trials [RCTs], 13 non-RCTs), Stratton et al concluded that enteral nutritional support can increase total energy and protein intake and raise serum albumin concentrations by an average of 0.23 g/dL with no adverse effects on electrolyte status (serum phosphate and potassium) (Am J Kidney Dis. 2005;46:387-405).
Results from the French Intradialytic Nutrition Evaluation study (FINEs) have provided further insights into effects from long-term use of nutritional supplementations in chronic hemodialysis patients with muscle wasting (J Am Soc Nephrol. 2007;18:2583-2591).This RCT involving 186 subjects showed that oral and combined oral–parenteral methods of supplement delivery have similar effects with regard to mortality and improvement of nutritional markers in chronic hemodialysis patients with muscle wasting, as long as equal and adequate amounts of protein and calories are provided.
Exercise. Numerous exercise regimens, including aerobic exercise, resistance exercise, or a combination of both, have been suggested as nutritional interventions in maintenance dialysis patients (J Am Soc Nephrol. 2007;18:1845-1854).
The rationale for such intervention is that exercise can induce significant physiological, functional, and psychological benefits without serious adverse events, as has been shown in healthy adults, elderly patients, and those who are frail and/or have chronic disease (J Gerontol A Biol Sci Med Sci. 2002;57:M262-M282, Am J Kidney Dis. 2005;45:912-916, and Am J Nephrol. 2005;25:352-364).
Overall, the available studies indicate that the presumed beneficial effects of resistance exercise, such as improvements in muscle quality and quantity, strength, and physical functioning, are not consistently observed in maintenance dialysis patients. Further research is necessary to understand both the observed lack of obvious benefits and the strategies that could lead to improved exercise regimens.
Anabolic agents. Besides the well-documented benefits of growth hormone in children with CKD, short-term administration to dialysis patients results in anabolic responses. Most if not all long-term studies indicate a significant increase in lean body mass in maintenance hemodialysis patients treated with growth hormone.
Significant improvements in body composition and physical function have been reported in hemodialysis patients who are given nandrolone decanoate (J Am Soc Nephrol. 2006;17:2307-2314). In addition, increases in cross-sectional area of the quadriceps muscle (by MRI measurements) and in lean body mass (by dual-energy x-ray absorptiometry) were also noted. Curiously, combining resistance exercise with nandrolone decanoate did not improve the beneficial effects of the drug.
Appetite stimulants. Examples of pharmacologic agents that may stimulate appetite include megestrol acetate, dronabinol, cyproheptadine, melatonin, thalidomide, and ghrelin. While most of these agents have not been studied systematically in maintenance dialysis patients with muscle wasting, they have been used in other catabolic illnesses.
Megestrol acetate has been associated with such side effects as hypogonadism, impotence, and increased risk of thromboembolism. In maintenance hemodialysis patients, megestrol acetate can stimulate appetite and induce small increases in serum albumin, but large-scale prospective studies are needed to assess whether any of the previously mentioned agents provides adjunctive nutritional therapy for maintenance dialysis patients.
The available evidence suggests that the imbalance between protein synthesis and degradation in patients undergoing dialysis can be compensated for by various anabolic strategies. Nutritional supplementation, administered orally or parenterally, is effective in the treatment of PEW.
Resistance or endurance exercise, while effective in the short term, seems to lack consistent evidence in improving lean body mass over the long term. Various anabolic agents are shown to increase visceral protein concentrations as well as muscle mass and strength simultaneously.
Additional larger-scale RCTs of anabolic interventions, used individually or in combination, should be performed to assess their efficacy on quality of life, morbidity, and mortality of maintenance dialysis patients.
Additional information on this topic will be presented at the National Kidney Foundation (NKF) 2010 Spring Clinical Meetings in Orlando, Fla. For additional information, go to www.nkfclinicalmeetings.org or contact the NKF at 800.622.9010 or via e-mail at [email protected].
Dr. Ikizler is Catherine McLaughlin Hakim Professor of Medicine and Medical Director of the Outpatient Dialysis Unit at Vanderbilt University in Nashville.