Epstein M, Parving H H, Ruilope L M
Department of Medicine, University of Miami School of Medicine, FL, USA.
Blood Press Suppl. 1997;2:52-7.
End-stage renal disease (ESRD) is a major public health problem worldwide. The past decade has witnessed increased interest and investigative attention on therapeutic manoeuvres to retard the progression of renal disease. Reduction of albuminuria is regarded as a surrogate endpoint, because this phenomenon seems to be associated with preservation of GFR (principal endpoint) in diabetic nephropathy. Studies from our laboratory suggest that reduction in albuminuria during ACE inhibition constitutes a predictor of an attenuated rate of decline in GFR in early diabetic nephropathy. Because the rate of decline in kidney function is used to assess prognosis and the efficacy of therapy on progression of renal disease, a valid method for the determination of GFR is essential. During the last two decades, several radioactive and non-radioactive filtration markers have been validated and found to be both accurate and precise compared to inulin. Plasma clearance of such filtration markers is frequently applied in clinical trials in diabetic nephropathy because patients suffering from this complication frequently also suffer from diabetic cystopathy, precluding measurements of urine volume. Measurements of serum creatinine, creatinine clearance, calculated creatinine clearance by use of the Cockroft-Gault formula must all be regarded as surrogate measurements for glomerular filtration rate. Consequently, care must be taken to select appropriate filtration markers in order to rigorously evaluate therapeutic trials in progressive renal disease.
终末期肾病（ESRD）是一个全球性的重大公共卫生问题。在过去十年中，人们对延缓肾病进展的治疗手段越来越感兴趣，并给予了更多的研究关注。减少蛋白尿被视为一个替代终点，因为在糖尿病肾病中，这种现象似乎与肾小球滤过率（主要终点）的维持有关。我们实验室的研究表明，在早期糖尿病肾病中，使用血管紧张素转换酶抑制剂（ACEI）期间蛋白尿的减少是肾小球滤过率下降速率减缓的一个预测指标。由于肾功能下降速率用于评估预后以及治疗对肾病进展的疗效，因此一种有效的肾小球滤过率测定方法至关重要。在过去二十年中，几种放射性和非放射性滤过标志物已得到验证，并且与菊粉相比，它们被发现既准确又精确。此类滤过标志物的血浆清除率常用于糖尿病肾病的临床试验，因为患有这种并发症的患者常常也患有糖尿病膀胱病，这使得尿量测量变得不可行。血清肌酐、肌酐清除率以及使用Cockcroft - Gault公式计算的肌酐清除率的测量都必须被视为肾小球滤过率的替代测量方法。因此，在评估进行性肾病的治疗试验时，必须谨慎选择合适的滤过标志物。
