Enric Vilar1, Capella Boltiador2, Adie Viljoen3, Ashwini Machado4, Ken Farrington5. 1. Renal Unit and Department of Postgraduate Medicine, School of Life Sciences, University of Hertfordshire, Hatfield, United Kingdom; and enric.vilar@nhs.net. 2. Department of Pathology, Lister Hospital, Stevenage, United Kingdom; Department of Biological, Biomedical, and Analytical Sciences, University of the West of England, Bristol, United Kingdom. 3. Department of Pathology, Lister Hospital, Stevenage, United Kingdom; 4. Renal Unit and. 5. Renal Unit and Department of Postgraduate Medicine, School of Life Sciences, University of Hertfordshire, Hatfield, United Kingdom; and.
Abstract
BACKGROUND AND OBJECTIVES: Cystatin C is a 13.3 kD middle molecule of similar size to β2-microglobulin and a marker of GFR in CKD. This study aimed to determine cystatin C kinetics in hemodialysis to understand whether 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 β2-microglobulin (reduction ratios ± SD are 39% ± 11 and 51% ± 11). Cystatin C rebounded to 95% ± 5% 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 m(2) 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 variation will limit use of cystatin C to predict residual renal function in advanced kidney disease.
BACKGROUND AND OBJECTIVES:Cystatin C is a 13.3 kD middle molecule of similar size to β2-microglobulin and a marker of GFR in CKD. This study aimed to determine cystatin C kinetics in hemodialysis to understand whether 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 β2-microglobulin (reduction ratios ± SD are 39% ± 11 and 51% ± 11). Cystatin C rebounded to 95% ± 5% 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 m(2) 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 variation will limit use of cystatin C to predict residual renal function in advanced kidney disease.
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