A Role for Uric Acid in the Progression of Renal Disease

作者：Duk‐Hee Kang, Takahiko Nakagawa, Lili Feng, Susumu Watanabe, Lin Han, Marilda Mazzali, Luan D. Truong, Raymond Clement Harris, Richard J. Johnson · 发表于：Journal of the American Society of Nephrology · 年份：2002 · DOI：10.1097/01.asn.0000034910.58454.fd · 被引用次数：1312 · 研究领域：Gout, Hyperuricemia, Uric Acid、Eosinophilic Disorders and Syndromes、Case Reports on Hematomas

Hyperuricemia is associated with renal disease, but it is usually considered a marker of renal dysfunction rather than a risk factor for progression. Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results in hypertension, intrarenal vascular disease, and renal injury. This led to the hypothesis that uric acid may contribute to progressive renal disease. To examine the effect of hyperuricemia on renal disease progression, rats were fed 2% OA for 6 wk after 5/6 remnant kidney (RK) surgery with or without the xanthine oxidase inhibitor, allopurinol, or the uricosuric agent, benziodarone. Renal function and histologic studies were performed at 6 wk. Given observations that uric acid induces vascular disease, the effect of uric acid on vascular smooth muscle cells in culture was also examined. RK rats developed transient hyperuricemia (2.7 mg/dl at week 2), but then levels returned to baseline by week 6 (1.4 mg/dl). In contrast, RK+OA rats developed higher and more persistent hyperuricemia (6 wk, 3.2 mg/dl). Hyperuricemic rats demonstrated higher BP, greater proteinuria, and higher serum creatinine than RK rats. Hyperuricemic RK rats had more renal hypertrophy and greater glomerulosclerosis (24.2 +/- 2.5 versus 17.5 +/- 3.4%; P < 0.05) and interstitial fibrosis (1.89 +/- 0.45 versus 1.52 +/- 0.47; P < 0.05). Hyperuricemic rats developed vascular disease consisting of thickening of the preglomerular arteries w...