GFR estimation using cystatin C is not independent of body composition

Background. Cystatin C (CysC) is an endogenous marker of glomerular filtration rate (GFR) that is claimed to be unaffected by body composition. In this study, we tested this speculation. Methods: In 77 patients with chronic kidney disease (mean age, 65.1 +/- 11.9 [SD] years; mean indexed GFR, 45.7 +/- 28.6 mL/min/1.73m(2) [0.76 +/- 0.48 mL/s]), we evaluated kidney function (GFR) by means of inulin clearance. CysC level was determined by using a particle-enhanced turbidimetric immunoassay. Total lean (LM) and fat masses were measured by means of dual-energy x-ray absorptiometry. Multiple regression was used to analyze relationships between absolute GFR, LM, fat mass, demographic and anthropometric variables (age, sex, height, and weight), and CysC levels. Then prediction equations were built that included only CysC level or CysC level and LM. Their performance to predict absolute GFR was evaluated in a subset of patients with extreme body composition (LM or fat mass > +/- 1 SD of the entire sample). Results Only absolute GFR and LM significantly explained variance in CysC levels, and an equation including LM explained more variance in absolute GFR than an equation including CysC level alone. Consequently, the equation including LM performed better than the equation with only CysC level, especially in patients with extreme body composition, showing reduced bias and improved limits of agreement and accuracy (71.4% versus 51.4% of patients' predicted GFR did not deviate by >30% of GFR). Conclusion: LM is a previously unrecognized, but important, factor affecting CysC level, and GFR estimation improves when including LM. CysC level is not independent of body composition, as previously assumed, and hence accounting for body composition improves CysC-based GFR estimation.