Back to the Physiology: Renal Tubular Handling of Uric Acid and Emerging Strategies for Managing Hyperuricemia

Hyperuricemia is a common comorbidity of chronic kidney disease (CKD) and contributes to kidney dysfunction through mechanisms involving glomerular, tubular, and vascular injuries. Although hyperuricemia has traditionally been classified into overproduction and underexcretion types, recent evidence highlights the importance of intrarenal urate handling, particularly tubular reabsorption, in the pathogenesis of CKD. In this review, we revisit the physiology of renal urate transport and summarize the clinical evidence that links hyperuricemia to CKD progression. We also summarize the current evidence regarding urate-lowering therapies, mainly focusing on novel selective urate reabsorption inhibitors (SURIs) and kidney outcomes. Based on emerging data, we propose a refined classification of hyperuricemia in CKD that stratifies patients into glomerular under-filtration and tubular over-reabsorption subtypes using a novel index that integrates both glomerular filtration and tubular reabsorption. This new classification may better guide individualized treatment strategies for CKD patients with hyperuricemia.