Song Su, Meyer Marko, Türk Tobias R, Wilde Benjamin, Feldkamp Thorsten, Assert Roland, Wu Kun, Kribben Andreas, Witzke Oliver
Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Nephrol Dial Transplant. 2009 Apr;24(4):1157-61. doi: 10.1093/ndt/gfn626. Epub 2008 Nov 11.
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.
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.
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).
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.
在急性肾衰竭中，血清肌酐（SCR）和血尿素氮（BUN）对肾小球滤过率（GFR）的测定并不准确。血清胱抑素C（CYS）有可能成为一种更精确的GFR标志物。本研究的目的是比较SCR、BUN和CYS在检测小鼠急性肾衰竭方面的敏感性。
在缺血再灌注（I/R）损伤模型中，小鼠经历60分钟的左肾缺血和右肾切除术。在肾切除模型中，小鼠进行不同程度的肾切除：从单侧（3/6Nx）到双侧肾切除（BiNx）。术后2、12或24小时采集血样。
与假手术小鼠和3/6Nx小鼠相比，I/R模型中SCR、BUN和CYS在术后12小时和24小时显著升高（SCR P = 0.009；BUN P < 0.001，CYS P < 0.004）。3/6Nx小鼠和假手术小鼠的所有三种标志物之间没有显著差异。在分级肾切除中，BUN和CYS在4/6Nx小鼠术后12小时就已显著显示出肾功能丧失[BUN（mg/dl）：假手术组26.4±3.5，4/6Nx组52.3±13.4，P < 0.01；CYS（mg/l）：假手术组0.08±0.03，4/6Nx组0.15±0.04，P < 0.01]，而SCR仅在5/6Nx和BiNx小鼠术后24小时显著升高[SCR（mg/dl）：假手术组0.39±0.05，4/6Nx组0.52±0.07，P = 0.13，5/6Nx组1.00±0.29，P < 0.01]。在纵向实验中，CYS显示肾损伤显著更早且程度更大（2小时时：SCR升高57±15%，BUN升高40±16%，CYS升高295±143%，P <0.001）。
在小鼠模型中，CYS可作为肾功能可靠且精确的标志物。CYS比SCR更敏感，且比SCR和BUN更早显示肾损伤。
