Uricosuric Drugs: Once and Future Therapy for Hyperuricemia?
Uricosuric Drugs: Once and Future Therapy for Hyperuricemia?
Purpose of review: Although uricosuric agents provide the most time-honoured approach to the control of hyperuricemia, their place in the armamentarium has been eclipsed by that of xanthine oxidase inhibitors. This review considers the potential for uricosuric agents from the perspective of recent progress in the understanding of urate transport systems.
Recent findings: No new agents have yet become available, but promising new drugs are under development. Better understanding of the transporters URAT1 and ABCG2 in particular would appear to provide opportunities for more selective, better tolerated agents to increase the renal clearance of uric acid and thereby control hyperuricemia.
Summary: Conceptually, modest inhibition of renal tubular reabsorption should provide effective relief for the millions of individuals who are now hyperuricemic and who suffer from its principal consequence, gout.
Gout is the most common inflammatory arthropathy. According to the 2007–2008 National Health and Nutrition Examination Survey, the prevalence of gout among U.S. adults was 3.9% (8.3 million; 6.1 million men and 2.2 million women). Epidemiologic trends have shown that the incidence of gout is increasing, as it doubled between the 1960s and 1990s. Uric acid (or urate at physiologic pH) may serve multiple physiologic roles, including blood pressure regulation, immune enhancer and antioxidant/proxidant effects. Conversely, hyperuricemia has been linked strongly with hypertension, chronic kidney disease, atherosclerosis, diabetes and the metabolic syndrome as well as gout. Hyperuricemia may lead to urate crystal joint deposition resulting in acute gouty arthritis or chronic gouty arthropathy and tophi formation. Although largely influenced by environmental factors, hyperuricemia is also a genetic trait. Current therapy seeks to target these genetic factors that include mutations in the genes coding for urate transport proteins. This review will focus on the potential role of uricosuric agents on the urate transport proteins as well as their use in the contemporary management of gout.
Abstract and Introduction
Abstract
Purpose of review: Although uricosuric agents provide the most time-honoured approach to the control of hyperuricemia, their place in the armamentarium has been eclipsed by that of xanthine oxidase inhibitors. This review considers the potential for uricosuric agents from the perspective of recent progress in the understanding of urate transport systems.
Recent findings: No new agents have yet become available, but promising new drugs are under development. Better understanding of the transporters URAT1 and ABCG2 in particular would appear to provide opportunities for more selective, better tolerated agents to increase the renal clearance of uric acid and thereby control hyperuricemia.
Summary: Conceptually, modest inhibition of renal tubular reabsorption should provide effective relief for the millions of individuals who are now hyperuricemic and who suffer from its principal consequence, gout.
Introduction
Gout is the most common inflammatory arthropathy. According to the 2007–2008 National Health and Nutrition Examination Survey, the prevalence of gout among U.S. adults was 3.9% (8.3 million; 6.1 million men and 2.2 million women). Epidemiologic trends have shown that the incidence of gout is increasing, as it doubled between the 1960s and 1990s. Uric acid (or urate at physiologic pH) may serve multiple physiologic roles, including blood pressure regulation, immune enhancer and antioxidant/proxidant effects. Conversely, hyperuricemia has been linked strongly with hypertension, chronic kidney disease, atherosclerosis, diabetes and the metabolic syndrome as well as gout. Hyperuricemia may lead to urate crystal joint deposition resulting in acute gouty arthritis or chronic gouty arthropathy and tophi formation. Although largely influenced by environmental factors, hyperuricemia is also a genetic trait. Current therapy seeks to target these genetic factors that include mutations in the genes coding for urate transport proteins. This review will focus on the potential role of uricosuric agents on the urate transport proteins as well as their use in the contemporary management of gout.
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