Mussap Michele, Dalla Vestra Michele, Fioretto Paola, Saller Alois, Varagnolo Mariacristina, Nosadini Romano, Plebani Mario
Department of Laboratory Medicine, University of Padova, Padova, Italy.
Kidney Int. 2002 Apr;61(4):1453-61. doi: 10.1046/j.1523-1755.2002.00253.x.
Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Inulin and 51Cr-EDTA plasma clearances are considered the gold standard methods for estimating GFR. Unfortunately, these methods require specialized technical personnel over a period of several hours and high costs. In clinical practice, serum creatinine is the most widely used index for the noninvasive assessment of GFR. Despite its specificity, serum creatinine demonstrates an inadequate sensitivity, particularly in the early stages of renal impairment. Recently, cystatin C, a low molecular mass plasma protein freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of changes in GFR. This study was designed to test whether serum cystatin C can replace serum creatinine for the early assessment of nephropathy in patients with type 2 diabetes.
The study was performed on 52 Caucasian type 2 diabetic patients. Patients with an abnormal albumin excretion rate (AER) were carefully examined to rule out non-diabetic renal diseases by ultrasonography, urine bacteriology, microscopic urine analysis, and kidney biopsy. Serum creatinine, serum cystatin C, AER, serum lipids, and glycosylated hemoglobin (HbA1c) were measured. GFR was estimated by the plasma clearance of 51Cr-EDTA. In addition the Cockcroft and Gault formula (Cockcroft and Gault estimated GFR) was calculated.
Cystatin C serum concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger (r = 0.84) than those between serum creatinine and GFR (r = 0.65) and between Cockcroft and Gault estimated GFR and GFR (r = 0.70). As GFR decreased from 120 to 20 mL/min/1.73 m2, cystatin C increased more significantly that serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C (90%) was significantly better than those of serum creatinine (77%) and Cockcroft and Gault estimated GFR (85%) in discriminating between type 2 diabetic patients with normal GFR (>80 mL/min per 1.73 m2) and those with reduced GFR (<80 mL/min/1.73 m2). In particular, the cystatin C cut-off limit of 0.93 mg/L corresponded to a false-positive rate of 7.7% and to a false-negative rate of 1.9%; the serum creatinine cut-off limit of 87.5 micromol/L corresponded to a false-positive rate of 5.8% and to a false-negative rate of 17.0%.
Cystatin C may be considered as an alternative and more accurate serum marker than serum creatinine or the Cockcroft and Gault estimated GFR in discriminating type 2 diabetic patients with reduced GFR from those with normal GFR.
肾小球滤过率（GFR）是评估健康及患病状态下肾功能的最佳综合指标。菊粉清除率和51铬-乙二胺四乙酸（51Cr-EDTA）血浆清除率被视为估算GFR的金标准方法。遗憾的是，这些方法需要专业技术人员操作数小时，且成本高昂。在临床实践中，血清肌酐是用于GFR无创评估的最广泛使用的指标。尽管血清肌酐具有特异性，但其敏感性不足，尤其是在肾功能损害的早期阶段。最近，胱抑素C，一种低分子量血浆蛋白，可自由通过肾小球滤过，几乎完全被肾小管细胞重吸收和分解代谢，已被提议作为GFR变化的一种新的、非常敏感的血清标志物。本研究旨在测试血清胱抑素C是否可替代血清肌酐用于2型糖尿病患者肾病的早期评估。
对52例白种人2型糖尿病患者进行了研究。对白蛋白排泄率（AER）异常的患者进行了仔细检查，通过超声检查、尿液细菌学检查、尿液显微镜分析和肾活检排除非糖尿病性肾脏疾病。测量了血清肌酐、血清胱抑素C、AER、血脂和糖化血红蛋白（HbA1c）。通过51Cr-EDTA血浆清除率估算GFR。此外，还计算了Cockcroft和Gault公式（Cockcroft和Gault估算的GFR）。
随着GFR下降，胱抑素C血清浓度逐渐升高。胱抑素C倒数与GFR之间的总体关系（r = 0.84）比血清肌酐与GFR之间的关系（r = 0.65）以及Cockcroft和Gault估算的GFR与GFR之间的关系（r = 0.70）显著更强。当GFR从120降至20 mL/min/1.73 m2时，胱抑素C升高比血清肌酐更显著，在测量的GFR范围内，与肌酐相比发出更强的信号。在区分GFR正常（>80 mL/min per 1.73 m2）的2型糖尿病患者和GFR降低（<80 mL/min/1.73 m2）的患者时，血清胱抑素C的最大诊断准确性（90%）显著优于血清肌酐（77%）和Cockcroft和Gault估算的GFR（85%）。特别是，胱抑素C的截断值为0.93 mg/L时，假阳性率为7.7%，假阴性率为1.9%；血清肌酐截断值为87.5 micromol/L时，假阳性率为5.8%，假阴性率为17.0%。
在区分GFR降低的2型糖尿病患者和GFR正常的患者时，胱抑素C可被视为比血清肌酐或Cockcroft和Gault估算的GFR更准确的替代血清标志物。
