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


METHODS
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.
Renal Unit and Department of Postgraduate Medicine, School of Life Sciences, University of Hertfordshire, Hatfield, United Kingdom; and enric.vilar@nhs.net.
Enric
E
Vilar
Department of Pathology, Lister Hospital, Stevenage, United Kingdom; Department of Biological, Biomedical, and Analytical Sciences, University of the West of England, Bristol, United Kingdom.
Capella
C
Boltiador
Department of Pathology, Lister Hospital, Stevenage, United Kingdom;
Adie
A
Viljoen
Renal Unit and.
Ashwini
A
Machado
Renal Unit and Department of Postgraduate Medicine, School of Life Sciences, University of Hertfordshire, Hatfield, United Kingdom; and.
Ken
K
Farrington
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001830:Body Surface Area; D001834:Body Water / Q000378:metabolism; D055316:Cystatin C / Q000097:blood*; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D017583:Hemodiafiltration; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008970:Molecular Weight; D011237:Predictive Value of Tests; D006435:Renal Dialysis
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C
GFR; cystatin C; hemodialysis; kinetics