Sustained, moderately severe
hyperuricemia and severe uricosuria were produced in male Wistar rats by feeding dietary supplements of
oxonic acid (0.4 gm. per day) and
uric acid (0.6 gm per day). After 1 month, the kidneys showed the previously described histologic features of
urate-blockade nephropathy characterized by intratubular deposits, tubular injury, and an exudative response consisting of neutrophilic granulocytes with early tophus formation. After 36 and 52 weeks of
hyperuricemia, and with no gross evidence of
renal failure, the kidneys showed a predominantly interstitial mononuclear cell infiltrate around regenerated tubules, an increase in interstitial fibrous tissue, infrequent renal tophi, and renal stones. The glomeruli and blood vessels appeared completely normal. There was no evidence of
arthritis and no other target organ damage was detected. The chronic renal changes present in this animal model of induced
hyperuricemia resemble those seen in human gouty nephropathy. The evolution of the experimental
urate nephropathy observed during 1 year suggests that a primary acute inflammatory tubular injury is followed by a diffuse chronic
interstitial nephritis and that the glomeruli and blood vessels are not primarily involved in the renal disease. This animal model may provide the opportunity to study factors influencing the renal sequelae of sustained
hyperuricemia.