Hyperuricemia and chronic kidney disease: to treat or not to treat

Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.

摘要 高尿酸血症在慢性肾脏病（chronic kidney disease, CKD）患者中极为常见，在需接受透析的患者群体中患病率可达50%。高尿酸血症可继发于慢性肾脏病所致的肾小球滤过率（glomerular filtration rate, GFR）降低。然而，高尿酸血症也可先于肾脏病发生，并可预测慢性肾脏病的发病风险。针对高尿酸血症动物模型的实验研究表明，可溶性尿酸与结晶态尿酸均可引发严重肾损伤，其病理特征表现为缺血、肾小管间质纤维化及炎症反应。但多数孟德尔随机化研究并未证实尿酸与慢性肾脏病之间存在因果关系，而相关临床试验的结果也存在较大差异。本文针对上述临床与遗传学研究的阴性结果提出了潜在解释，包括结晶态尿酸、细胞内尿酸以及黄嘌呤氧化酶活性在尿酸介导的肾损伤中的作用。同时，本文还提出了未来临床试验的研究方向，以及慢性肾脏病患者高尿酸血症的诊疗算法。