Background: The optimal criteria to select individuals with type 1 diabetes mellitus (T1D) and albuminuric or normoalbuminuric diabetic kidney disease (DKD), who are at risk of rapid kidney function decline, for clinical trials are unclear. Methods: This study analyzed data from the Preventing Early Renal Loss in Diabetes (PERL) clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with T1D and early-to-moderate DKD. Rates of iohexol GFR (iGFR) and estimated GFR (eGFR) decline during the three-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (N=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min/1.73 m2/year) in the absence of a history of albuminuria (N=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated. Results: Rates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (-3.56 [95% confidence intervals {CI} -3.17, -3.95] versus -2.35 [95% CI: -1.86, -2.84] ml/min/1.73 m2/year, p=0.001). Results were similar for iGFR decline, although the difference was not significant (p=0.07). Within the history of albuminuria group, the rate of eGFR decline was -5.30 (95% CI -4.52, -6.08) ml/min/1.73m2/year in participants with severely increased albuminuria as compared to -2.97 (95% CI 2.44, -3.50) and -2.32 (95% CI -1.61, -3.03) ml/min/1.73m2/year in those with moderately increased or normal/mildly increased albuminuria at baseline (p<0.001). Conclusions: Severely increased albuminuria at screening is a powerful criterion for selecting persons with T1D at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose but it can still identify individuals with T1D who will lose kidney function more rapidly than expected from physiological aging. Clinical Trail Registration: ClinicalTrials.gov, NCT02017171 Copyright © 2024 by the American Society of Nephrology

中文翻译：

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白蛋白尿和肾功能快速下降是 1 型糖尿病肾脏临床试验的选择标准


背景：选择患有 1 型糖尿病 （T1D） 和白蛋白尿或正常白蛋白尿的糖尿病肾病 （DKD） 个体进行临床试验的最佳标准尚不清楚，这些患者有肾功能快速下降的风险。方法： 本研究分析了预防糖尿病早期肾功能损失 （PERL） 临床试验的数据，该试验调查了别嘌呤醇是否减缓了 T1D 和早期至中度 DKD 患者的肾功能下降。通过线性混合效应回归比较三年研究期间碘海醇 GFR （iGFR） 和估计 GFR （eGFR） 下降率，比较基于中度或重度尿白蛋白升高病史 （N=394） 的参与者和基于近期肾功能快速下降史 （≥3 ml/min/1.73 m2/年） 的参与者，在没有白蛋白尿史 （N=124）。还评估了试验期间基线白蛋白尿与 iGFR/eGFR 下降之间的关联。结果：试验期间，有白蛋白尿史的参与者的 eGFR 下降率高于有肾功能快速下降病史的参与者 （-3.56 [95% 置信区间 {CI} -3.17， -3.95] 对比 -2.35 [95% CI： -1.86， -2.84] ml/min/1.73 m2/年，p=0.001）。iGFR 下降的结果相似，但差异不显著 （p=0.07）。在白蛋白尿病史中，尿白蛋白严重升高的参与者的 eGFR 下降率为 -5.30 （95% CI -4.52， -6.08） ml/min/1.73m2/年，而基线时尿白蛋白中度增加或正常/轻度增加的参与者为 -2.97 （95% CI 2.44， -3.50） 和 -2.32 （95% CI -1.61， -3.03） ml/min/1.73m2/年 （p<0.001）。 结论： 筛查时尿白蛋白严重升高是选择肾功能下降高风险的 T1D 患者的有力标准。无白蛋白尿史的 eGFR 快速下降史对此效果较差，但它仍然可以识别因生理衰老而比预期更快地丧失肾功能的 T1D 个体。临床试验注册：ClinicalTrials。gov， NCT02017171 版权所有 © 2024 美国肾脏病学会