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Effects of allopurinol on renal function in patients with diabetes: a systematic review and meta-analysis.

ABSTRACT:

Background/objective

Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus.

Methods

We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis.

Results

Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment (p = 0.0001) or placebo (p < 0.00001). Moreover, the levels of 24-hour urine protein were significantly lower in the allopurinol group (p < 0.00001). The subgroup analysis of Scr showed that the Scr of patients with an allopurinol treatment duration of fewer than six months was significantly lower than that of the control group (p = 0.03). No significant difference in adverse events (AEs) was identified between the treatment and control groups.

Conclusions

Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients' renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.

SUBMITTER: Luo Q

PROVIDER: S-EPMC9307109 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsTo compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.Methods and resultsPubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).ConclusionsData from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.Systematic review registrationPROSPERO registration CRD42018089744.

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