Keum Youngshin, Caramori Maria Luiza, Cherney David Z, Crandall Jill P, de Boer Ian H, Lingvay Ildiko, McGill Janet B, Polsky Sarit, Pop-Busui Rodica, Rossing Peter, Sigal Ronald J, Mauer Michael, Doria Alessandro
Research Division, Joslin Diabetes Center, Boston, Massachusetts.
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Clin J Am Soc Nephrol. 2025 Jan 1;20(1):62-71. doi: 10.2215/CJN.0000000000000567. Epub 2024 Nov 18.
Severely increased urinary albumin excretion rate is an effective criterion to select persons with type 1 diabetes at high risk of GFR decline for enrollment in clinical trials. A history of rapid GFR decline is less effective but can be used to extend clinical trials to person with normoalbuminuric diabetic kidney disease. These findings have immediate implications for the design of clinical trials of novel renoprotective interventions in type 1 diabetes.
The optimal criteria to select individuals with type 1 diabetes mellitus and albuminuric or normoalbuminuric diabetic kidney disease, who are at risk of rapid kidney function decline, for clinical trials are unclear.
This study analyzed data from the Preventing Early Renal Loss in Diabetes clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with type 1 diabetes mellitus and early-to-moderate diabetic kidney disease. Rates of iohexol GFR (iGFR) and eGFR decline during the 3-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min per 1.73 m per year) in the absence of a history of albuminuria (=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated.
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 (CIs), −3.17 to −3.95] versus −2.35 [95% CI, −1.86 to −2.84] ml/min per 1.73 m per year, = 0.001). The results were similar for iGFR decline, although the difference was not significant ( = 0.07). Within the history of albuminuria group, the rate of eGFR decline was −5.30 (95% CI, −4.52 to −6.08) ml/min per 1.73 m per year in participants with severely increased albuminuria as compared with −2.97 (95% CI, 2.44 to −3.50) and −2.32 (95% CI, −1.61 to −3.03) ml/min per 1.73 m per year in those with moderately increased or normal/mildly increased albuminuria at baseline ( < 0.001).
Severely increased albuminuria at screening is a powerful criterion for selecting persons with type 1 diabetes mellitus 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 type 1 diabetes mellitus who will lose kidney function more rapidly than expected from physiological aging.
: NCT02017171.
尿白蛋白排泄率严重升高是筛选1型糖尿病中肾小球滤过率（GFR）下降高风险人群以纳入临床试验的有效标准。GFR快速下降史的有效性稍低，但可用于将临床试验扩展至正常白蛋白尿性糖尿病肾病患者。这些发现对1型糖尿病新型肾脏保护干预措施的临床试验设计具有直接意义。
对于筛选1型糖尿病且有白蛋白尿或正常白蛋白尿性糖尿病肾病、存在肾功能快速下降风险的个体以纳入临床试验，最佳标准尚不清楚。
本研究分析了“糖尿病早期肾脏损失预防”临床试验的数据，该试验调查了别嘌醇是否能减缓1型糖尿病和早期至中度糖尿病肾病患者的肾功能下降。通过线性混合效应回归比较了基于中度或重度白蛋白尿病史（≥394）入选的参与者与基于近期肾功能快速下降史（≥3 ml/min/1.73m²/年）且无白蛋白尿病史（=124）入选的参与者在3年研究期间的碘海醇GFR（iGFR）和估算GFR（eGFR）下降率。还评估了基线白蛋白尿与试验期间iGFR/eGFR下降之间的关联。
有白蛋白尿病史的参与者在试验期间的eGFR下降率高于有肾功能快速下降史的参与者（-3.56 [95%置信区间（CI），-3.17至-3.95] 对比 -2.35 [95%CI，-1.86至-2.84] ml/min/1.73m²/年，P = 0.001）。iGFR下降的结果相似，尽管差异不显著（P = 0.07）。在白蛋白尿病史组中，与基线时白蛋白尿中度升高或正常/轻度升高的参与者相比，严重白蛋白尿升高的参与者的eGFR下降率为-5.30（95%CI，-4.52至-6.08）ml/min/1.73m²/年，而中度升高或正常/轻度升高的参与者的eGFR下降率分别为-2.97（95%CI，2.44至-3.50）和-2.32（95%CI，-1.61至-3.03）ml/min/1.73m²/年（P < 0.001）。
筛查时严重白蛋白尿升高是筛选1型糖尿病肾功能下降高风险人群的有力标准。无白蛋白尿病史的eGFR快速下降史在此目的上有效性稍低，但仍可识别出1型糖尿病中肾功能丧失速度比生理衰老预期更快的个体。
NCT02017171 。
