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 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.


CONCLUSIONS
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.
Bökenkamp
A
A
Bonn University Children's Hospital, Germany. a.boekenkamp@uni-bonn.de
Ciarimboli
G
G
Dieterich
C
C
D000818:Animals; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D015853:Cysteine Proteinase Inhibitors / Q000097:blood*; D005919:Glomerular Filtration Rate; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009392:Nephrectomy; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley
C525030:CST3 protein, human; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D003404:Creatinine