Submitted to: Journal of Renal Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2007
Publication Date: 9/1/2007
Citation: Castaneda-Sceppa, C., Sarnak, M.J., Wang, X., Greene, T., Madero, M., Kusek, J.W., Beck, G., Kopple, J.D., Levey, A.S., Menon, V. 2007. Role of Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease. Journal of Renal Nutrition. 17(5):314-322.
Interpretive Summary: Malnutrition is common in the early stages of chronic kidney disease (CKD), and rises steadily with its progression. Indicators of nutritional status such as serum albumin and muscle mass are powerful predictors of morbidity and mortality in CKD. Muscle mass confers a survival advantage in kidney failure. The loss of muscle mass with CKD may be the result of an imbalance between catabolic and anabolic signals. Although the mechanisms underlying muscle wasting are not well understood, adipocyte-derived proteins, called adipokines, may play an important role, given that they mediate insulin resistance and inflammation in kidney disease. The objectives of this study were to examine the relationship of the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by CRP), and insulin resistance (as measured by homeostasis model assessment; HOMA) with muscle mass (measured as arm muscle area) in CKD stages 3 and 4 enrolled in the Modification of Diet in Renal Disease (MDRD) Study. After adjustment for BMI, higher levels of leptin and CRP were associated with lower arm muscle area. There was a trend toward an inverse relationship of adiponectin with arm muscle area, but no independent association with HOMA. However, it must be noted that the most important determinant of arm muscle area in this cohort was BMI, and that BMI was also correlated with leptin, adiponectin, CRP, and HOMA, thus potentially confounding these relationships. In conclusion, our findings suggest a potential role for adipocyte-derived factors in the development of muscle wasting, a powerful prognostic indicator in CKD. Further studies are needed to understand the mechanisms underlying malnutrition in earlier stages of CKD, and to develop preventive interventions.
Technical Abstract: OBJECTIVE: Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by homeostasis model assessment, HOMA), implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass. PATIENTS AND SETTING: The Modification of Diet in Renal Disease Study cohort of people with CKD stages 3 and 4 was used for analysis (N = 780). MAIN OUTCOME MEASURES: Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome). RESULTS: Arm muscle area was 39 +/- 15 cm(2) (mean +/- SD), and adiponectin levels were 13 +/- 7 microg/mL. Median and interquartile range (IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) for HOMA. Higher leptin (beta coefficient and 95% confidence interval, -6.9 [-8.7 to -5.1], P < .001) and higher CRP (beta coefficient and 95% confidence interval, -2.7 [-3.9 to -1.4], P < .001) were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P = .07), but no association with HOMA (P = .80). CONCLUSION: Leptin and CRP were associated with lower muscle mass in subjects with CKD at stages 3 and 4. Further studies are needed to understand the mechanisms underlying these associations, and to develop targeted interventions for this patient population.