Diuretic-induced hyperuricemia and gout
- Michael A Becker, MD
Michael A Becker, MD
- Section Editor — Crystal Diseases
- Professor Emeritus of Medicine
- University of Chicago Pritzker School of Medicine
Hyperuricemia is a relatively common finding in patients treated with a loop or thiazide diuretic and may, over a period of time, lead to gouty arthritis [1-4]. Diuretics reduce urate excretion by both directly and indirectly increasing urate reabsorption and decreasing urate secretion [2,5-7]; the effect is dose dependent (figure 1). Treatment of asymptomatic hyperuricemia is not necessary. If diuretic-induced gout occurs, it is usually treated with a urate-lowering drug such as allopurinol.
The pathogenesis, epidemiology, and an overview of treatment of diuretic-induced hyperuricemia and gout are presented in this topic. The pathophysiology, clinical manifestations, diagnosis, and treatment of acute gouty arthritis as well as the prevention of recurrent gout are discussed separately. (See "Pathophysiology of gouty arthritis" and "Clinical manifestations and diagnosis of gout" and "Treatment of acute gout" and "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi" and "Prevention of recurrent gout: Lifestyle modification and other strategies for risk reduction", section on 'Hypertension and diuretics'.)
The proximal tubule is the major site of urate handling; both secretion and reabsorption occur in this segment, with the net effect being reabsorption of most of the filtered urate (figure 2 and figure 3) [2,8-15]. Urate enters the proximal tubular cell from peritubular capillary blood through organic anion transporters 1 and 3 (OAT1 and OAT3) located on the basolateral membrane, and is secreted from the cell into the tubular fluid through solute carrier (SLC) family members SLC17A1 and SLC17A3, multidrug resistance protein 4 (MRP4), and ATP-binding cassette G2 (ABCG2) located on the luminal membrane. Urate reabsorption from the tubular fluid into the cell is mediated by urate transporter 1 (URAT1), OAT4, and OAT10, located on the luminal membrane, and from the cell back to the peritubular capillary blood through glucose transporter 9 (GLUT9) located on the basolateral membrane.
Loop and thiazide diuretics decrease urate excretion by increasing net urate reabsorption; this can occur either by enhanced reabsorption or by reduced secretion [2,5]. Two mechanisms have been proposed as contributing to diuretic-induced hyperuricemia [2,5-7]:
●A direct effect of diuretics on promoting urate reabsorption by the proximal tubule
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