Gout Drug Disappoints as Renoprotective Agent in Type 1 Diab
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Reduction of serum urate with allopurinol didn't have much clinical benefit for those with type 1 diabetes and kidney disease, according to the Preventing Early Renal Loss in Diabetes (PERL) trial.

In a double-blind trial, researchers 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.

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. 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. The mean urinary albumin excretion rate after washout was 40% higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups.

Conclusively, 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 was found.

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