Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes
Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes
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DOI：
10.1056/nejmoa1916624
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发表时间：
2020-06-25
影响因子：
158.5
通讯作者：
Mauer, M.
中科院分区：
文献类型：
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作者：
Doria, A.;Galecki, A. T.;Mauer, M.
背景：较高的血清尿酸水平与糖尿病肾病的风险增加有关。别嘌呤醇降低血清尿酸水平可能减缓1型糖尿病和早至中度糖尿病肾病患者肾小球滤过率（GFR）的下降。方法：在一项双盲试验中，我们随机分配1型糖尿病患者，血清尿酸水平至少为每分升4.5 mg，估计GFR为每分钟每1.73 m(2)体表面积40.0至99.9 ml，并且有糖尿病肾病的证据，接受别嘌呤醇或安慰剂。主要终点是基线调整后的GFR，用碘醇测量，经过3年加上2个月的洗脱期。次要结局包括每年基于碘醇的GFR的下降和洗脱后尿白蛋白排泄率的下降。安全性也进行了评估。结果267例患者接受别嘌呤醇治疗，263例患者接受安慰剂治疗。平均年龄51.1岁，平均糖尿病病程34.6年，平均糖化血红蛋白水平8.2%。别嘌呤醇组基于碘醇的平均基线GFR为68.7 ml / min / 1.73 m(2)，安慰剂组为67.3 ml / min / 1.73 m(2)。在干预期间，别嘌呤醇组的平均血清尿酸水平从6.1毫克/分升降至3.9毫克/分升，而安慰剂组保持在6.1毫克/分升。洗脱后，基于碘hexol的平均GFR组间差异为0.001 ml / min / 1.73 m(2)（95%置信区间[CI]， -1.9 ~ 1.9； P= 0.99）。别嘌呤醇组基于碘hexol的GFR平均下降为-3.0 ml / min / 1.73 m(2) /年，安慰剂组为-2.5 ml / min / 1.73 m(2) /年（组间差异为-0.6 ml / min / 1.73 m(2) /年）；95% CI, -1.5 ~ 0.4)。别嘌呤醇组洗脱后尿白蛋白平均排泄率比安慰剂组高40% （95% CI, 0 ~ 80）。两组严重不良事件发生频率相似。结论：我们未发现别嘌呤醇降低血清尿酸对1型糖尿病和早至中度糖尿病肾病患者肾脏预后有临床意义的益处。
BACKGROUNDHigher 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.METHODSIn 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 m(2) 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.RESULTSA 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 m(2) in the allopurinol group and 67.3 ml per minute per 1.73 m(2) 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 m(2) (95% confidence interval [CI], -1.9 to 1.9; P= 0.99). The mean decrease in the iohexolbased GFR was -3.0 ml per minute per 1.73 m(2) per year with allopurinol and -2.5 ml per minute per 1.73 m(2) per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m(2) 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.CONCLUSIONSWe 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.