Alterations of renal function during dietary-induced hyperuricemia in the rat

Hyperuricemia was induced in rats ingesting a diet supplemented with 2 1/2+ uric acid and 5% oxonic acid (an inhibitor of hepatic uricase activity). After seven days, inulin clearance (CIn) and superficial nephron glomerular filtration rate (SNFR) were significantly lower than values recorded in healthy rats (CIn:0.94 +/- 0.10 vs. 3.61 +/- 0.13 ml/min/kg of body wt; SNFR: 54.9 +/- 3.2 vs. 129.7 +/- 6.7 nl/min/kg of body wt). Filtration rate reduction was accompanied by an increased concentration of urate in renal tissue. Gross examination of the kidney revealed the presence of whitish streaks containing negatively birefringent crystals throughout the medulla and papilla. Histological examination revealed dilatation of the collecting ducts with flattening of the epithelium and intraluminal crystalline deposits. Intraluminal hydrostatic pressure was markedly higher than that observed in healthy rats in both proximal (21.5 +/- 1.7 vs. 11.4 +/- 0.3 mm Hg) and distal convoluted tubules (20.3 +/- 2.0 vs. 7.6 +/- 0.5 mm Hg). In another group of rats ingesting a similar diet, CIn was reduced to 1.49 +/- 0.20 ml/min/kg of body wt. Partial or complete restoration of CIn toward normal was effected within seven additional days by the oral ingestion of a large volume of an alkali solution (CIn:2.63 +/- 0.44 ml/min/kg of body wt) or by the cessation of treatment with oxonic-uric acid (CIn: 4.70 +/- 0.28 ml/min/kg of body wt). These results demonstrate that oxonic/uric acid-induced hyperuricemia is accompanied by severe filtration rate reduction, and they suggest strongly that intraluminal obstruction, via the deposition of uric acid, plays an important role in its pathogenesis.