The Efficacy And Safety Of Allopurinol On Diabetic Nephropathy With Asymptomatic Hyperuricemia:A Meta-analysis

Objective: Lots of studies have indicated that serum uric acid(SUA)level is closely related to diabetic nephropathy(DN)progression presently.Whether it should be given uric acid lowering therapy for patients with diabetic nephropathy with asymptomatic hyperuricemia,however,there is still no unified views.So we evaluate the efficacy and safety of allopurinol on diabetic nephropathy with asymptomatic hyperuricemia by a meta-analysis of the randomized controlled trials(RCTs).Methods: Public published RCTs of comparing the effect of ULT with placebo or no treatment on DN with asymptomatic HUA of January 1950 to July 2016 were collected from PubMed,Cochrane Library database,MEDLINE,EMBASE,CNKI,Wanfang Data and so on.Relevant publications were included and analyzed according to the inclusion criteria by two reviewers separately,including urine protein quantification,serum creatinine,glomerular filtration rate,systolic pressure,diastolic pressure,progression to end-stage renal disease cases,uric acid and adverse reactions.The meta-analysis was measured with stata14.0 software.Mean difference(MD),standardized mean difference(SMD)and its 95% CI were used to evaluate continuous data,relative risk degree(RR)and its 95% CI were used to evaluate second classification data.The heterogeneity is expressed with I2.When there was no evidence of significant heterogeneity(P<0.1,I2>50%),effect sizes were decided using a fixed-effects model,and otherwise we utilized a random effects model.If the heterogeneity is too large,Egger test should be applied to verify the existence of publication bias.Results: We ultimately included 6 randomized controlled trials that conformed to the inclusion criteria,in which the treatment group and control group was 287 and 258 cases,respectively.In comparison with the control group,ULT with allopurinol is proved to the benefit of decreasing proteinuria [MD=-0.47,95%CI=(-0.63,-0.31)] by 3 articles;5 of which are good to lowering blood creatinine [MD=-0.53,95%CI=(-0.70,-0.35)];and another 5 of which make for reducing both systolic [MD=-2.90,95%CI=(-4.60,-1.19)] and diastolic [MD=-2.07,95%CI=(-3.40,-0.75)] blood pressure.But there are 2 articles do not illustrate that ULT with allopurinol can reduce the risk of diabetic nephropathy progressing to end-stage renal disease [MD=0.43,95%CI=(0.18,1.01)] clearly.There is no sufficient evidence to evaluate the effect of ULT with allopurinol on GFR,while its risk to adverse events is still safe.Conclusion: ULT with allopurinol may delay the progression of diabetic nephropathy safely,but it appears that large amount of stricter,multi-center high-quality randomized double-blind controlled trials are necessary to provide the curative effect and safety of uric acid treatment on diabetic nephropathy.