Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications

Asymptomatic hyperuricaemia (HU) is considered a pathogenic factor in multiple disease contexts, but a causative role is only proven for the crystalline form of uric acid in gouty arthritis and urate nephropathy. Epidemiological studies document a robust association of HU with hypertension, cardiovascular disease (CVD) and CKD progression, but CKD-related impaired uric acid (UA) clearance and the use of diuretics that further impair UA clearance likely accounts for these associations. Interpreting the available trial evidence is further complicated by referring to xanthine oxidase inhibitors as urate-lowering treatment, although these drugs inhibit other substrates, so attributing their effects only to HU is problematic. In this review we provide new mechanistic insights into the biological effects of soluble and crystalline UA and discuss clinical evidence on the role of asymptomatic HU in CKD, CVD and sterile inflammation. We identify research areas with gaps in experimental and clinical evidence, specifically on infectious complications that represent the second common cause of death in CKD patients, referred to as secondary immunodeficiency related to kidney disease. In addition, we address potential therapeutic approaches on how and when to treat asymptomatic HU in patients with kidney disease and where further interventional studies are required.