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Cystatin C in a rat model of end-stage renal failure
A Bökenkamp1, G Ciarimboli, C Dieterich
1Bonn University Children's Hospital, Germany. a.boekenkamp@uni-bonn.de
Background:
Cystatin C (MW 13kDa) serum concentration reflects glomerular filtration rate better than creatinine. Like other low-molecular weight proteins it is not eliminated by dialysis. Still, cystatin C serum concentrations do not rise progressively in end-stage renal failure and rarely exceed 10 mg/L (i.e. 8 times the upper limit of normal).
Objective:
To study cystatin C kinetics in a rat model of end-stage renal failure.
Methods:
Sequential bilateral nephrectomy was performed seven days apart in 13 male Sprague-Dawley rats as described by Levine and Saltzman. Serum cystatin C (Cystatin C PET-kit, DAKO), creatinine and total protein were measured in daily intervals after the second nephrectomy. Linearity of the anti-human cystatin C assay for rat cystatin C was tested using dilutions of uremic rat serum. Rats were sacrificed for signs of severe uremia on days 10 (n=5), 11 (n=4) and 12 (n = 5).
Results:
At baseline, mean (+/- SE) cystatin C was 1.59+/-0.041 mg/L, creatinine 19.6+/-1.2 micromol/L. Following bilateral nephrectomy, cystatin C immediately rose to 3.82+/-0.15 mg/L, creatinine to 312+/-20 micromol/L. During the following days, cystatin C concentration stabilized to 4 mg/L approximately whereas creatinine continued to rise to 822+/-185 kmol/L on day 12. Correction for the decrease in serum total protein concentration from 48.9+/-2.3 g/L to 37.4+/-3.6 g/L did not alter these results.
Conclusion:
The kinetics of cystatin C and creatinine in this rat model of end-stage renal failure are in accordance with human data suggesting a change in cystatin C production or extra-renal elimination in severe chronic uremia.