美国加斯林糖尿病中心Alessandro Doria团队分析了使用别嘌呤醇降低1型糖尿病患者血清尿酸水平对肾功能的影响。该成果发表在2020年6月25日出版的《新英格兰医学杂志》上。

较高的血清尿酸水平与糖尿病肾病风险增加相关。别嘌呤醇降低血清尿酸水平可减缓1型糖尿病和早中期糖尿病肾病患者肾小球滤过率（GFR）的降低。

在一项双盲试验中，研究组招募1型糖尿病患者，其血清尿酸水平至少为4.5 mg/dL，估计GFR为40.0-99.9 mL/min·1.73m²，伴糖尿病肾病。将其随机分组，其中267名接受别嘌呤醇治疗，263名接受安慰剂治疗。主要结局为3年2个月的洗脱期后，基于碘海醇测量的校正后GFR。

参与者的平均年龄为51.1岁，平均糖尿病病程为34.6年，平均糖化血红蛋白水平为8.2％。 别嘌呤醇组中基于碘海醇的平均基线GFR为68.7 mL/min·1.73m²，安慰剂组为67.3 mL/min·1.73m²。在干预期间，别嘌呤醇组的平均血清尿酸水平从6.1 mg/dL降至3.9 mg/dL，而安慰剂组则保持在6.1 mg/dL。

洗脱期过后，两组间基于碘海醇的平均GFR的组间差异为0.001 mL/min·1.73m²。别嘌呤醇组基于碘海醇的GFR平均每年减少3.0 mL/min·1.73m²，安慰剂组平均每年减少2.5 mL/min·1.73m²，差异不显著。别嘌呤醇组洗脱后的尿液白蛋白平均排泄率比安慰剂组高40％。两组间严重不良事件发生率相差不大。

总之，对于1型糖尿病和早中期糖尿病肾病患者，使用别嘌呤醇后血清尿酸降低，但并未发现对肾脏预后有临床益处。

附：英文原文

Title: Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

Author: Alessandro Doria, M.D., Ph.D., M.P.H.,, Andrzej T. Galecki, M.D., Ph.D.,, Cathie Spino, Sc.D.,, Rodica Pop-Busui, M.D., Ph.D.,, David Z. Cherney, M.D., Ph.D.,, Ildiko Lingvay, M.D.,, Afshin Parsa, M.D., M.P.H.,, Peter Rossing, M.D.,, Ronald J. Sigal, M.D., M.P.H.,, Maryam Afkarian, M.D., Ph.D.,, Ronnie Aronson, M.D.,, M. Luiza Caramori, M.D., Ph.D.,, Jill P. Crandall, M.D.,, Ian H. de Boer, M.D.,, Thomas G. Elliott, M.B., B.S.,, Allison B. Goldfine, M.D.,, J. Sonya Haw, M.D.,, Irl B. Hirsch, M.D.,, Amy B. Karger, M.D., Ph.D.,, David M. Maahs, M.D., Ph.D.,, Janet B. McGill, M.D.,, Mark E. Molitch, M.D.,, Bruce A. Perkins, M.D., M.P.H.,, Sarit Polsky, M.D., M.P.H.,, Marlon Pragnell, Ph.D.,, William N. Robiner, Ph.D.,, Sylvia E. Rosas, M.D., M.S.C.E.,, Peter Senior, M.B., B.S., Ph.D.,, Katherine R. Tuttle, M.D.,, Guillermo E. Umpierrez, M.D.,, Amisha Wallia, M.D.,, Ruth S. Weinstock, M.D.,, Chunyi Wu, Ph.D.,, and Michael Mauer, M.D.

Issue&Volume: 2020-06-24

Abstract: Abstract

Background

Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease.

Methods

In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed.

Results

A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], 1.9 to 1.9; P=0.99). The mean decrease in the iohexol-based GFR was 3.0 ml per minute per 1.73 m2 per year with allopurinol and 2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, 0.6 ml per minute per 1.73 m2 per year; 95% CI, 1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups.

Conclusions

We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease.

DOI: 10.1056/NEJMoa1916624

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1916624