Reanalysis of CARES study to investigate the changes of estimated glomerular filtration rate after long-term febuxostat or allopurinol treatment in gout patients

Hyperuricemia is elevated uric acid in the blood, above a certain level, crystal deposits may occur leading to pain and swelling in the joints known as gout. Hyperuricemia is also associated with various health conditions such as heart disease, diabetes mellitus, and kidney disease. Of these, chronic kidney disease (CKD) has been identified as a major public health concern worldwide. Hyperuricemia is significantly associated with development and progression of CKD. Several possible mechanisms explaining this relationship have been suggested, however, it is still unclear whether hyperuricemia plays a causative role in the progression of CKD, or is an indirect marker of decreased kidney function.
Under the hypothesis that hyperuricemia is a potentially modifiable risk factor for the progression of CKD, there has been an expectation that the control of hyperuricemia using urate-lowering therapy (ULT) will have a beneficial effect on slowing the progression of CKD. There have been numerous small, single-center studies that have shown that use of ULT delayed CKD progression in patients with hyperuricemia. However, three recent multicenter, randomized controlled trials, not targeting gout patients, have not shown beneficial effect of a ULT on slowing the progression of CKD. Therefore, there is controversy over the role of ULT in the progression of CKD.

高尿酸血症（Hyperuricemia）指血液尿酸水平超出特定阈值，此时可出现尿酸盐结晶沉积，进而引发关节疼痛肿胀，即痛风。高尿酸血症还与多种健康状态相关，包括心脏病、糖尿病（diabetes mellitus）及肾脏病等。其中，慢性肾脏病（CKD）已被认定为全球范围内的重大公共卫生问题。高尿酸血症与慢性肾脏病的发生及进展显著相关。尽管已有多项假说阐释二者关联的潜在机制，但目前仍未明确高尿酸血症是否直接推动慢性肾脏病进展，或是仅为肾功能下降的间接标志物。基于“高尿酸血症是慢性肾脏病进展的潜在可干预危险因素”这一假说，学界曾预期通过降尿酸治疗（ULT）控制高尿酸血症，可延缓慢性肾脏病的进展。此前已有多项小型单中心研究证实，降尿酸治疗可延缓高尿酸血症患者的慢性肾脏病进展。然而近期三项针对非痛风患者的多中心随机对照试验并未显示降尿酸治疗对慢性肾脏病进展具有延缓益处。因此，降尿酸治疗在慢性肾脏病进展中的作用尚存争议。