Supplementary Material for: The effect of allopurinol on renal outcomes in patients with diabetic kidney disease: A systematic review and meta-analysis

Background: Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol administration could be of therapeutic benefit in diabetic subjects. However, there has been controversy regarding the effects of allopurinol on DKD.
Objectives: The aim of our study is to investigate the efficacy of allopurinol on renal function in patients with DKD by meta-analysis of randomized controlled trials.
Method: PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2020. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was the change in albuminuria and serum UA. Two reviewers independently assessed for risk of bias and extracted data. Standardized mean difference (SMD) or weighted mean difference (WMD) was calculated with random effects models and was reported with corresponding 95% confidence intervals (CI). Grading of Recommendations Assessment, Development and Evaluation (GRADE) of the evidence was performed after meta-analysis. International prospective register of systematic reviews registration CRD42020219132.
Results:
From 642 potentially relevant citations, 3 studies were ultimately included. Our results showed evident reduction in serum UA after allopurinol intervention (WMD = -103.80, 95% CI -159.05, -48.55, I2= 76%; P = 0.04), with a high GRADE of evidence. However, allopurinol did not significantly improve GFR (WMD = 1.07, 95% CI -1.68, 3.82, I2= 33%; P = 0.45), with a moderate GRADE of evidence. There was no significant difference on improvement of albuminuria in patients of allopurinol and those in placebo groups (SMD = -0.26, 95% CI -1.03, 0.52, I2= 94%; P = 0.52), with a moderate GRADE of evidence.
Conclusions:
The present research showed that allopurinol did not significantly improve renal function and albuminuria in patients with DKD.

背景：高尿酸血症（Hyperuricemia）是糖尿病肾病（Diabetic Kidney Disease, DKD）进展的独立危险因素。既往动物实验与队列研究表明，给予别嘌醇可使糖尿病患者获得治疗获益，但关于别嘌醇对DKD的影响仍存在争议。
研究目的：本研究旨在通过随机对照试验（Randomized Controlled Trial, RCT）的荟萃分析（meta-analysis），探讨别嘌醇对DKD患者肾功能的改善效果。
研究方法：检索PubMed、EMBASE及Cochrane Library数据库自建库至2020年10月的相关文献。主要结局指标为肾小球滤过率（glomerular filtration rate, GFR）的变化值，次要结局指标为白蛋白尿（albuminuria）与血清尿酸（serum UA, UA）的变化值。由2名研究者独立评估文献偏倚风险并提取研究数据。采用随机效应模型计算标准化均数差（Standardized Mean Difference, SMD）或加权均数差（Weighted Mean Difference, WMD），并报告对应的95%置信区间（Confidence Interval, CI）。荟萃分析完成后，采用推荐分级、评估、制定与评价（Grading of Recommendations Assessment, Development and Evaluation, GRADE）体系对证据质量进行分级。本研究已在国际系统评价前瞻性注册平台完成注册，注册号为CRD42020219132。
研究结果：初筛得到642篇潜在相关文献，最终纳入3项研究。结果显示，别嘌醇干预后患者血清UA水平显著降低（WMD=-103.80，95%CI：-159.05~-48.55，I²=76%；P=0.04），证据质量为高级。然而，别嘌醇未能显著改善患者GFR（WMD=1.07，95%CI：-1.68~3.82，I²=33%；P=0.45），证据质量为中级。别嘌醇组与安慰剂组患者的白蛋白尿改善情况无显著差异（SMD=-0.26，95%CI：-1.03~0.52，I²=94%；P=0.52），证据质量为中级。
研究结论：本研究表明，别嘌醇未能显著改善DKD患者的肾功能与白蛋白尿水平。