Cystatin C in a rat model of end-stage renal failure

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 10mg/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 μmol/L. Following bilateral nephrectomy, cystatin C immediately rose to 3.82 ± 0.15 mg/L, creatinine to 312 ± 20 μmol/L. During the following days, cystatin C concentration stabilized to 4 mg/L approximately whereas creatinine continued to rise to 822 ± 185 μmol/L on day 12. Correction for the decrease in serum total protein concentration from 48.9 ± 2.3g/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.