Comment on “Higher Serum Creatinine Concentrations in Black Patients with Chronic Kidney Disease

The article “Higher Serum Creatinine Concentrations in Black Patients with Chronic Kidney Disease: Beyond Nutritional Status and Body Composition” by Hsu et al . (1) suggests that a greater creatinine generation rate on the basis of larger muscle mass does not explain the higher serum creatinine levels observed in black prevalent hemodialysis patients. In our opinion, this conclusion is not tenable given the limitations of the study design and method.The most critical methodologic shortcoming of Hsu's approach is the choice of 50-kHz single-frequency bioimpedance analysis (BIA) and the way it was used to correct for, as the authors stated, “body composition.” Creatinine is predominantly derived from skeletal muscle creatine (endogenous) and, to a lesser extent, from the diet (exogenous); therefore, when attempting to correct for creatinine generation rate by adjusting for body composition, the appropriate body compartment to adjust for is skeletal muscle. 50-kHz single-frequency BIA is not a valid method for delineating body fluid compartments in individuals with altered hydration (2); however, accurate delineation of intracellular volume is essential for estimation of muscle mass by BIA, although even the most accurate BIA-derived measure of intracellular volume will never be a perfect reflection of muscle volume, because BIA cannot distinguish between intracellular water from muscle cells and intracellular water from other tissues, such as the viscera, skin, and adipose tissue. Notwithstanding this, BIA can be a valid tool for estimation of body composition, including in patients with chronic kidney disease (3), and population-specific bioimpedance-based regression models can provide valid muscle mass estimates (4). Of note, though, in individuals with an altered intracellular-to-extracellular volume ratio ( e.g ., patients with chronic kidney disease), the 0/∞-kHz parallel Cole-Cole model is the method of choice for determining body water compartmentalization, as has been comprehensively shown by Gudivaka et al . (2). An adjustment …