Verinurad (RDEA3170): A Comprehensive Monograph on a Selective URAT1 Inhibitor from Gout to Cardiorenal Indications

Introduction to Verinurad and URAT1 Inhibition

The Pathophysiology of Hyperuricemia and Gout

Hyperuricemia is a prevalent metabolic disorder defined by elevated serum uric acid (sUA) concentrations, typically at or above 6.8 mg/dL, which represents the saturation point of monosodium urate at physiological temperature and pH.[1] This condition is the central prerequisite for the development of gout, a debilitating form of inflammatory arthritis characterized by the deposition of monosodium urate crystals within joints, soft tissues, and organs.[1] The clinical manifestations of gout range from acute, intensely painful inflammatory flares to chronic, progressive disease leading to joint destruction, disfiguring tophi, and persistent pain.[2] The fundamental cause of hyperuricemia in the vast majority of patients—approximately 90%—is not the overproduction of uric acid but rather its inadequate renal excretion.[2] This critical physiological detail has established the renal urate transport system as a primary and highly logical target for therapeutic intervention.

The Role of Renal Urate Transporter 1 (URAT1) in Urate Homeostasis