Serum Cystatin C in Mouse Models: a Reliable and Precise Marker for Renal Function and Superior to Serum Creatinine

Background: Serum creatinine (SCR) and blood urea nitrogen (BUN) determine the glomerular filtration rate (GFR) improperly in acute renal failure. Serum cystatin C (CYS) has the potential to be a more precise marker for GFR. The aim of this study was to compare the sensitivity of SCR, BUN and CYS with respect to the detection of acute renal failure in mice.

Methods: In an ischaemia reperfusion (I/R) injury model, mice suffered 60-min left kidney ischaemia and right nephrectomy. In a nephrectomy model, mice were nephrectomized to a different extent: from unilateral (3/6Nx) to bilateral nephrectomy (BiNx). Blood samples were collected 2, 12 or 24 h post-op.

Results: SCR, BUN and CYS increased significantly in the I/R-model in comparison to sham mice and 3/6Nx mice at 12 and 24 h post-op (SCR P = 0.009; BUN P < 0.001 and CYS P < 0.004). There were no significant differences in all three markers between 3/6Nx and sham-operated mice. In graded nephrectomy, BUN and CYS showed already significantly the loss of kidney in 4/6Nx mice 12 h post-op [BUN (mg/dl): sham 26.4 +/- 3.5, 4/6Nx 52.3 +/- 13.4, P < 0.01; CYS (mg/l): sham 0.08 +/- 0.03, 4/6Nx 0.15 +/- 0.04, P < 0.01], whereas SCR was only significantly increased in 5/6Nx and BiNx mice 24 h post-op [SCR (mg/dl): sham 0.39 +/- 0.05, 4/6Nx 0.52 +/- 0.07, P = 0.13, 5/6Nx 1.00 +/- 0.29, P < 0.01]. In the longitudinal experiment, CYS showed the renal damage significantly earlier and to a larger extent (2 h: SCR 57 +/- 15%, BUN 40 +/- 16%, CYS 295 +/- 143%, P <0.001).

Conclusions: CYS can be used as a reliable and precise marker for renal function in mouse models. CYS is more sensitive than SCR, and it shows renal damage earlier than SCR and BUN.