Effects Of Uric-acid-lowering Therapy In Hyperuricemia On Progression Of Chronic Kidney Disease And Cardiovascular Disease: A Meta-analysis Of Randomized Controlled Trials

Background Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease, but there is still uncertain about whether lowering urate can slow the progression of chronic kidney disease and cardiovascular disease. Therefore, we performed a meta-analysis of randomized controlled trials to assess the benefits and risks of uric-acid-lowering therapy in patients with hyperuricemia on renal function and cardiac function.Methods We searched randomized controlled trials from PubMed, EMBASE, Conchrane, SCI, CBM, CNKI, CPVIP, Wanfang and so on. Two researchers selected studies, assessed risk of bias and extracted data independently according to the inclusion and exclusion criteria. Meta-analysis was conducted for RCTs meeting the criteria.Results 46 RCTs with 3301 patients were included in this study.28 articles of them were related to the study of renal function, and 20 articles were related to the study of cardiac function. (1) Compared with the control group, uric-acid-lowering therapy group could significantly reduce serum creatinine(SMD=-0.949,95% CI:-1.306～-0.594, Z= 5.23, P= 0.000), reduce the level of blood urea nitrogen(SMD=-0.570,95%CI:-0.843～-0.296, Z=4.08, P= 0.000), and improve glomerular filtration rate (SMD=0.439,95%CI:0.258～0.619, Z=4.76, P= 0.000). (2) Uric-acid-lowering therapy group could markedly improve cardiac function, reduce left ventricular end diastolic diamete (SMD=-0.868,95%CI:-1.134～-0.601, Z=6.37, P=0.000), and increase left ventricular ejection fraction (SMD=1.055,95%CI: 0.793～1.317, Z=7.89, P= 0.000),compared to the control group. (3) Compared with the control group, uric-acid-lowering therapy group could significantly lower systolic blood pressure (SMD=-0.471,95%CI:-0.735～-0.208, Z=3.51, P= 0.000), improve flow-mediated dilation (SMD=1.032,95%CI:0.324～1.74, Z=2.86, P= 0.004) and decrease hypersensitive C-reactive protein (SMD=-0.927,95%CI:-1.545～-0.308, Z=2.94, P= 0.003). There is no statistically significant difference between the two groups in the diastolic blood pressure (SMD=-0.18,95%CI:-0.49～0.14, Z=1.09, P=0.277).(4) Regression analysis and subgroup analysis showed that there is no statistically significant association between the effect of hypouricemic therapy on renal function and cardiac function and age of patients, sample size, duration of follow-up, baseline serum uric acid, baseline serum creatine and urate-lowering strategy(P>0.05).(5) Compared with the control group, uric-acid-lowering therapy group was vulnerable to have gastrointestinal reaction, and patients with allopurinol was easy to have drug rash.Conclusion Uric-acid-lowering therapy in hyperuricemia is able to delay the progression of chronic kidney disease and improve cardiac function. However, the uric-acid-lowering therapy may have gastrointestinal reaction, and allopurinol has higher incidence of drug rash. Given the uncertainties in the evidence base, more large-scale randomized controlled trials are needed to establish the exact effect of urate lowering therapy on the outcome of CKD.