Urate (UA)

Urate, the ionized form of uric acid, is the final metabolic product of purine catabolism in humans, who lack the functional uricase enzyme found in most other mammals [1]. While the kidneys are the primary route for urate excretion, the gastrointestinal tract plays a significant role, accounting for approximately one-third of total urate elimination through active secretion into the intestinal lumen [2, 4]. In the lumen, urate anions are subject to degradation by the gut microbiota or can be targeted by therapeutic interventions to manage systemic levels [3]. High levels of urate are associated with the formation of monosodium urate crystals, leading to gout and contributing to the progression of chronic kidney disease [1, 2]. Therapeutic targeting of urate in the intestinal lumen involves the use of oral urate-degrading enzymes, such as the investigational drug ALLN-346 [3]. These enzymes oxidize luminal urate into allantoin, a much more soluble compound that is easily excreted in the stool or urine [3]. By depleting urate in the gut, these therapies create a concentration gradient that pulls systemic urate from the blood into the intestine, a process sometimes referred to as enteric dialysis [2, 3]. This approach provides a non-renal pathway for lowering serum uric acid, which is particularly beneficial for patients with impaired kidney function who cannot tolerate or do not respond to traditional uricosuric agents [3, 4].

Other names

Uric acidHydrogen urate2,6,8-trioxypurineLithic acid

Enzymatic oxidation of luminal urate to allantoin, which facilitates enteric excretion and creates a concentration gradient to lower systemic serum uric acid levels.