Carlos Enrique Méndez Landa1. 1. Department of Nephrology, General Hospital and Medical Unit Ambulatory Care, Mexican Institute of Social Security, Mexico City, Mexico.
Abstract
BACKGROUND: From a clinical point of view, uric acid has been dismissed as a cause of injury and renal progression, and the mechanisms by which uric acid directly causes renal injury have not been fully understood. Hyperuricemia is associated with metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases. Although it remains controversial whether hyperuricemia is a causal factor for kidney disease, kidneys play a major role in the regulation of serum uric acid levels. SUMMARY: Similar to the management of other substances, renal uric acid management occurs mainly in the proximal tubule. The elevation of uric acid in blood is mainly due to an increase in its intake or a defect in its secretion. The mechanisms of renal damage go beyond the deposition of crystals at the tubular level; in this sense, renal damage also contributes to the production of chemotactic cytokines, cell proliferation, and inflammation, with the development of afferent arteriolopathy, glomerular hypertrophy and tubulointersticial fibrosis. Nevertheless, whether or not hyperuricemia plays a causal role or simply is a marker arising in the course of each related disorder remains unresolved. Although a strong relationship between hyperuricemia and metabolic syndrome has been established through animal and epidemiological studies, the potential pathophysiological mechanisms by which uric acid contributes to this disease state are just beginning to be explained and clarified. Key Messages: Experimental studies performed in animals have limitations due to the differences that exist between humans and other mammals in purine metabolism and in renal uric acid handling. Additional experimental studies aimed at evaluating the effects of lowering urate levels on the courses of these disorders are warranted in the future.
BACKGROUND: From a clinical point of view, uric acid has been dismissed as a cause of injury and renal progression, and the mechanisms by which uric acid directly causes renal injury have not been fully understood. Hyperuricemia is associated with metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases. Although it remains controversial whether hyperuricemia is a causal factor for kidney disease, kidneys play a major role in the regulation of serum uric acid levels. SUMMARY: Similar to the management of other substances, renal uric acid management occurs mainly in the proximal tubule. The elevation of uric acid in blood is mainly due to an increase in its intake or a defect in its secretion. The mechanisms of renal damage go beyond the deposition of crystals at the tubular level; in this sense, renal damage also contributes to the production of chemotactic cytokines, cell proliferation, and inflammation, with the development of afferent arteriolopathy, glomerular hypertrophy and tubulointersticial fibrosis. Nevertheless, whether or not hyperuricemia plays a causal role or simply is a marker arising in the course of each related disorder remains unresolved. Although a strong relationship between hyperuricemia and metabolic syndrome has been established through animal and epidemiological studies, the potential pathophysiological mechanisms by which uric acid contributes to this disease state are just beginning to be explained and clarified. Key Messages: Experimental studies performed in animals have limitations due to the differences that exist between humans and other mammals in purine metabolism and in renal uric acid handling. Additional experimental studies aimed at evaluating the effects of lowering urate levels on the courses of these disorders are warranted in the future.