Removal and rebound kinetics of cystatin C in high-flux hemodialysis and hemodiafiltration

Abstract

Background and objectives Cystatin C is a 13.3 kD middle molecule of similar size to b2-microglobulin and a marker of GFR in CKD. This study aimed to determine cystatin C kinetics in hemodialysis to understandwhether blood concentrations may predict residual renal function and middle-molecule clearance. Design, setting, participants, & measurements Cystatin C removal and rebound kinetics were studied in 24 patients on high-flux hemodialysis or hemodiafiltration. To determine whether cystatin C concentrations are predictable, an iterative two-pool mathematical model was applied. Results Cystatin C was cleared effectively, although less than b2-microglobulin (reduction ratios±SD are 39%±11 and 51%±11). Cystatin C rebounded to 95%65% of predialysis concentration by 12 hours postdialysis. The two-pool kinetic model showed excellent goodness of fit. Modeled extracellular cystatin C pool volume is smaller than that predicted, comprising 25.5%±9.2 of total body water. Iterated parameters, including nonrenal clearance, showed wide interindividual variation. Modeled nonrenal clearance was substantially higher than renal clearance in this population at 25.1±6.6 ml/min per 1.73 m2 body surface area. Conclusions Plasma cystatin C levels may be used to measure middle-molecule clearance. Levels rebound substantially postdialysis and plateau in the interdialytic period. At low GFR, nonrenal clearance predominates over renal clearance, and its interindividual variationwill limit use of cystatin C to predict residual renal function in advanced kidney disease.