1. Serum urate reduction with allopurinol was not shown to clinically benefit kidney function among patients with type 1 diabetes and early-to-moderate diabetic kidney disease.
2. Serum creatinine did not improve following serum urate reduction with allopurinol.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The lifetime risk of diabetic kidney disease among patients with type 1 diabetes is high. Interventions such as glucose control and blood pressure control are implemented to slow the progression of diabetic kidney disease. However, glomerular filtration rate (GFR) preservation with these interventions is limited. Serum urate levels predict albuminuria and early GFR decline. In two small-clinical trials that were conducted previously, reduction in serum urate levels slowed GFR progression among patients with moderate chronic kidney disease. One fourth of these patients also had diabetes. The purpose of this study was to test whether serum urate level reduction with allopurinol therapy slowed GFR decline in patients with type 1 diabetes and early-to-moderate diabetic kidney disease. The results demonstrated that patients with serum urate level reduction did not have improved kidney function when compared to patients with serum urate control. One limitation of this randomized trial was time period of the study. Urate promotes damage over a long-term exposure period. Therefore, the timeframe of this trial may not be sufficient to capture the actual effects of serum urate levels on kidney damage. Nonetheless, this study was strengthened by the high treatment adherence in both groups.
In-Depth [randomized controlled trial]: This randomized control trial enrolled 609 patients in a multicenter study from 16 sites and three countries. Patients included in this study had a diagnosis of type 1 diabetes, evidence of kidney disease and a serum urate level of at least 45 mg per deciliter. The exclusion criteria for the study included having a GFR lower than 40.0 mL per minute per 1.73m2. Patients were randomized in a 1:1 ratio to receive either oral placebo or allopurinol. The primary outcome of the study was the iohexol-based GFR after three years and a two-month washout period to assess kidney function. The iohexol-based GFR measurement was more sensitive for the detection of GFR changes and decreased at similar rates for patients in the allopurinol group and the placebo group. The mean iohexol-based GFR at the end of the two-month washout period between both groups were similar, at 61.2 mL per minute per 1.73m2 (between group difference, 0.001 mL per minute per 1.73m2; 95% confidence interval [CI], -1.9 to 1.9). Furthermore, there were no differences between the two groups for serum creatinine doubling or progression to end-stage renal disease. Concisely, there were 11 patients in the placebo group and 13 patients in the allopurinol group (between group difference, 1.2; 95% CI, 0.5 to 2.9). Taken together, the reduction of serum urate with allopurinol did not clinically benefit kidney outcome in patients with diabetes type 1 and early-to-moderate diabetic kidney disease.
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