This week we'll discuss creatinine clearance.
1.What is the Cockcroft-Gault formula, and how does it assist in determining the etiology of oliguria?
2.Why is knowing the creatinine clearance so important to establishing renal function?
3.Besides creatinine, are there other accepted substances used for measuring GFR?
4.What novel measurements may predict GFR?
1 什么是Cockcroft-Gault方程，此方程是如何确定少尿的？
2 为什么肌酐清除率对肾功的评价如此重要？
3 除肌酐外，是否还有其他物质可用于测定肾小球滤过率？
4 确定肾小球滤过率新颖的测量手段是什么？
参考答案（请战友指正)
1 什么是Cockcroft-Gault方程，此方程是如何确定少尿的？
Cockcroft-Gault方程根据血清肌酐浓度预测肌酐清除率，肌酐清除率= [(140-年龄) x 体重（kg）]/72 x 血清肌酐浓度。由于女患肌肉肌酐产生量少，因此在对女患计算时应乘系数0.85。此方程计算结果与实测肌酐清除率有良好的相关性（相关系数=0.83），被广泛用于评估肾功。部分上，这个从肌酐清除率演化来的方程是测定肾小球滤过率的最有效手段。此方程的计算必须与尿液采集相对比（标准24小时采样比较繁琐耗时），已经证明30分，1小时和2小时肌酐清除率可以精确评估肾小球滤过率变化。
2 为什么肌酐清除率对肾功的评价如此重要？
肌酐是肌肉中肌酸的代谢产物，在肾脏滤过时很少被吸收和分泌。此特性使对其的测量可反映肾小球滤过率，而肾小球滤过率是评价肾功最常用的指标之一。如果肾小球滤过率下降，最可能是由于肾小球受损伤后滤过面积减少导致净滤过率减少。因此肌酐清除率下降显示肾小球滤过率下降可用于评估肾脏疾病的严重程度和进程。最近使用西咪替丁阻断肾小管肌酐分泌可提高此方法对评估肾小球滤过率的精确性。
3 除肌酐外，是否还有其他物质可用于测定肾小球滤过率？
菊粉，一种多糖类物质，可被肾脏自由滤过，不被肾脏重吸收、分泌、合成和代谢，是评估肾小球滤过率的标准物质。根据传统方法持续静脉输注和同时采集血和尿液样品，菊粉清除率可精确测定肾小球滤过率。然而，其干预条件很繁琐，不太适合临床上使用，因此肌酐清除率仍然是最常用的检测肾小球滤过率的方法。
4 确定肾小球滤过率新颖的测量手段是什么？
尽管肌酐和菊粉一直用于精确研究肾小球滤过率，但他们依赖于尿样中肌酐和菊粉的精确收集。实际上，通常需要快速的诊断信息。Tsushima等发现CT检查时碘化对比剂的药物代谢动力学与菊粉相似，于是假设碘化对比剂可用于测定肾脏指数包括单位肾容积清除率 (alpha/V)和血管容积分数(fvv).在对正常和糖尿病患者两组患者进行评估后，作者观察到一次性注入对比剂后进行连续扫描，对比剂呈现时间衰减曲线。从CT计算出的肾脏清除率和校正后肾容积和肾小球滤过率在两组患者中高度相关。作者因此认为，动态CT可对肾功提供可靠信息。进一步工作经进一步完善此新的方法。
最近，曾有人提出用血清半胱氨酸蛋白酶抑制剂(SCyst)作为肾小球滤过率的标志，Chantrel 等在140名患者中应用菊粉清除率比较了SCyst、血清肌酐、Cockcroft方程测定肾小球滤过率的差别，虽然各指标间相关性良好，但根据实验绘出的SCyst和肌酐清除率图表，与理论模型有所偏差，这提示可能SCyst不只是被滤过。作者因此认为，虽然SCyst不及肌酐清除率在检测肾功衰竭方面敏感，但可用于肌酐清除率抬高患者的确定实验.
英文参考答案：
1 What is the Cockcroft-Gault formula, and how does it assist in determining the etiology of oliguria?
The Cockcroft-Gault formula (2) predicts creatinine clearance based on serum creatinine, and is derived by: Creatinine Clearance = [(140-age (yrs)) x kg]/72 x Serum Creatinine. The result is multiplied by a factor of 0.85 in women to account for the reduced production of muscle creatinine.
The formula, noted to have a favorable correlation coefficient with measured creatinine clearances (correlation coefficient=0.83), has greatly assisted in evaluating renal function. In part, this stems from creatinine clearance being the most efficient measure of glomerular filtration (GFR). This formulaic computation must then be compared to urine collections (and the standard 24 hr urine collection is cumbersome and time consuming), 30 minute, 1 hr and 2 hr creatinine clearances have been shown to be accurate in estimating changes in GFR (3).
2 Why is knowing the creatinine clearance so important to establishing renal function?
Creatinine, a substance produced by metabolism of creatine in skeletal muscle, is filtered with minimal absorption and secretion. These characteristics allow its measurement to be reflective of glomerular filtration (GFR), which is perhaps the most commonly used index of functioning renal mass. A reduction in GFR in disease states is most often due to a decrease in net permeability resulting from a loss of filtration surface area due to glomerular injury. As such, a decreased in GFR, as demonstrated by decreased creatinine clearance, can assess the severity and course of renal disease. Recently, the use of cimetidine to block renal tubular creatinine secretion has improved the evaluation of GFR using this modality (4).
3 Besides creatinine, are there other accepted substances used for measuring GFR?
Inulin, a polysaccharide which is freely filtered and not reabsorbed, secreted, synthesized, or metabolized by the kidney, represents the gold standard for estimating glomerular filtration rate. Determined by conventional methods of continuous intravenous infusion and simultaneous blood and urine sample collections, inulin clearance yields an accurate measurement of GFR. However, it does represent a cumbersome intervention, perhaps too much so for routine clinical use, and thus creatinine clearance remains the most commonly used measurement.
4 What novel measurements may predict GFR as well?
While creatinine and inulin have been utilized to accurately study GFR, they depend on meticulous collection of urine creatinine or inulin. Often, more rapid diagnostic information is desirable. Tsushima et al. (5), noted that the iodinated contrast agents used for computed tomography (CT) have pharmacokinetics similar to inulin and hypothesized that it could be used as a physiologic measure of renal indices, including clearance per unit renal volume (alpha/V) and fractional vascular volume (fvv). In evaluating both normal and diabetic patients, the authors noted that sequential scanning of a single slice of kidney after a bolus injection of contrast material allowed for the construction of time-attenuation curves. A strong correlation was observed between renal clearance values, calculated from CT and corrected for renal volume, and GFR (r = 0.87; P < 0.0001) in both normal and diabetic individuals. The authors concluded that dynamic CT can provide reliable information on renal function. Further work will have to confirm the findings of this new modality.
Most recently, serum cystatin C (SCyst) has been proposed as an indicator of GFR. Chantrel et al. compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) in 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82). Although a good correlation was found between all indicators, when Cin and SCyst were plotted, the experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. As such, the authors concluded that although SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, it could be used as a confirmatory test for patients with elevated SCreat.
References:
1.Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. 1996;334(22):1448-60.
2.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
3.Sladen RN. Oliguria in the ICU. Systematic approach to diagnosis and treatment. Anesthesiol Clin North America 2000;18(4):739-52.
4.Kemperman FA, Silberbusch J, Slaats EH, et al. Follow-up of GFR estimated from plasma creatinine after cimetidine administration in patients with diabetes mellitus type 2. Clin Nephrol. 2000;54(4):255-60.
5.Tsushima Y, Blomley MJ, Kusano S, Endo K. Use of contrast-enhanced computed tomography to measure clearance per unit renal volume: a novel measurement of renal function and fractional vascular volume. Am J Kidney Dis 1999;33(4):754-60.
6.Chantrel F, Agin A, Offner M, et al. Comparison of cystatin C versus creatinine for detection of mild renal failure. Clin Nephrol 2000;54(5):374-81.
