Читать книгу Uric Acid in Chronic Kidney Disease - Группа авторов - Страница 22

A model for hyperuricemic nephropathy was described by Stavric, Johnson, and Brice. Hyperuricemia and uricosuria were induced in rats fed with uric acid and oxonic acid. After 1 day of hyperuricemia, animals had deposits of uric acid and urate crystals within collecting tubules of the renal papillae, and tubular cells were altered. By 10 days, there was an exudative response with further injury to epithelium [3]. Electron microscopic studies indicate that human neutrophils rapidly ingest monosodium urate crystals. Within neutrophils, the crystals are enclosed phagolvsosomes containing at least one hydrolase, acid phosphatase. There is dissolution of the membrane about the phagolysosome and release of contents into the cytoplasmic matrix leading to the lysis of the neutrophil itself. The urate crystal is thereby free to initiate injury in other cells [4]. Micropuncture studies demonstrate a decrease in the single-nephron glomerular filtration rate (GFR) associated with a twofold increase in tubular hydrostatic pressure. Pathologic examination shows numerous white streaks throughout the medulla and pyramids caused by intratubular deposition of acid uric and urate crystals. Secondary tubular atrophy, infiltration of inflammatory cells, and interstitial fibrosis have also been reported [2, 4].

Johnson’s work group has found that raising the uric acid level could induce oxidative stress and endothelial dysfunction, resulting in the development of both systemic and glomerular hypertension in association with elevated renal vascular resistance and reduced renal blood flow. In normal rats, there was activation of the renin-angiotensin system, with the development of vascular disease of the afferent arteriolar system (arteriolosclerosis) and glomerular hypertrophy, and over time mild interstitial disease and glomerulosclerosis [5].

There are 2 different types of renal diseases induced by uric acid: acute uric acid nephropathy and chronic urate nephropathy.