Zoccali Carmine, Provenzano Pasquale Fabio, Tripepi Giovanni, Carrara Fabiola, Mallamaci Francesca, Perna Annalisa, Delanaye Pierre, Ruggenenti Piero, Remuzzi Giuseppe
Renal Research Institute, New York, New York.
Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy.
Clin J Am Soc Nephrol. 2024 Oct 24;20(2):178-85. doi: 10.2215/CJN.0000000602.
GFR estimations are biased in patients with frank nephrotic syndrome, but the problem is uncharacterized in patients with non-nephrotic proteinuria. We investigated the bias and accuracy of eGFR formulas in patients with mild-to-moderate proteinuria participating in the ramipril in nondiabetic renal failure 1 and 2 trials. The CKD Epidemiology Collaboration 2009 and 2021 and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in moderate-to-severe proteinuria.
Creatinine-based GFR formulas introduce a substantial bias in GFR estimations in patients with frank nephrotic syndrome. The bias and accuracy of creatinine-based GFR estimates (eGFR) in patients with non-nephrotic proteinuria need better characterization.
We used data from the Ramipril in Nondiabetic Renal Failure (ramipril in nondiabetic renal failure [REIN] 1) and REIN 2 trials involving nondiabetic CKD patients with proteinuria to compare eGFRs derived from the CKD Epidemiology Collaboration formulas (with and without race) and the European Kidney Function Consortium equations with iohexol clearance (a gold-standard GFR measure, measured GFR [mGFR]). Bias was defined as the median difference between eGFR and mGFR while accuracy was assessed using P30 and P15 metrics, which represent the percentage of eGFR values within ±30% and ±15% of mGFR, respectively.
The median bias of the three formulas being compared did not differ, being minimal and in a strict range (0.04–0.05 ml/ml per min per 1.73 m) in the REIN 1 trial and (−0.04 to 0.03 ml/min per 1.73 m) in the REIN 2 trial. These findings were confirmed in analyses stratified by age and mGFR. The global accuracy of the three formulas regarding P30 % showed sufficient accuracy (P30 >75%) in the REIN 1 trial and all strata in the REIN 2 trial, but the mGFR stratum was <15 ml/min per 1.73 m.
The CKD Epidemiology Collaboration (with and without race) and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in patients with proteinuria. These formulas can be safely applied to nondiabetic CKD patients with moderate-to-severe proteinuria.
: This is a post hoc analysis of two trials, REIN 1 and 2, published about 20 years ago.
在患有明显肾病综合征的患者中，肾小球滤过率（GFR）估计值存在偏差，但在非肾病性蛋白尿患者中，这一问题尚未得到明确界定。我们在非糖尿病性肾衰竭1和2试验中，研究了轻度至中度蛋白尿患者中估算肾小球滤过率（eGFR）公式的偏差和准确性。慢性肾脏病流行病学协作组2009年和2021年的公式以及欧洲肾功能协会的公式在中度至重度蛋白尿患者中显示无显著偏差且准确性足够。
基于肌酐的GFR公式在明显肾病综合征患者的GFR估计中引入了实质性偏差。非肾病性蛋白尿患者中基于肌酐的GFR估计值（eGFR）的偏差和准确性需要更好地界定。
我们使用了非糖尿病性肾衰竭（REIN）1和REIN 2试验的数据，这些试验涉及有蛋白尿的非糖尿病慢性肾脏病患者，以比较慢性肾脏病流行病学协作组公式（有和没有种族因素）以及欧洲肾功能协会公式得出的eGFR与碘海醇清除率（一种金标准GFR测量值，实测GFR [mGFR]）。偏差定义为eGFR与mGFR之间的中位数差异，而准确性使用P30和P15指标进行评估，这两个指标分别代表eGFR值在mGFR的±30%和±15%范围内的百分比。
所比较的三个公式的中位数偏差没有差异，在REIN 1试验中偏差最小且在严格范围内（每分钟每1.73平方米0.04 - 0.05毫升/毫升），在REIN 2试验中为（每分钟每1.73平方米−0.04至0.03毫升）。这些发现在按年龄和mGFR分层的分析中得到了证实。关于P30%，这三个公式在REIN 1试验以及REIN 2试验的所有分层中显示出足够的准确性（P30>75%），但mGFR分层中每分钟每1.73平方米<15毫升。
慢性肾脏病流行病学协作组（有和没有种族因素）以及欧洲肾功能协会的公式在蛋白尿患者中显示无显著偏差且准确性足够。这些公式可安全应用于患有中度至重度蛋白尿的非糖尿病慢性肾脏病患者。
这是对大约20年前发表的两项试验REIN 1和REIN 2的事后分析。
