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Adult male Sprague-Dawley rats maintained on a low sodium diet were administered 100 mg of cyclosporine per kg b.wt. per day s.c. for 4 to 10 days. Serum urea nitrogen was significantly elevated by day 4 and continued to rise, whereas serum creatinine was not elevated above control until day 10. Morphologic examination of perfusion-fixed kidneys from cyclosporine-treated rats revealed focal areas of tubular atrophy and interstitial fibrosis in the outer cortex and a generalized increase in interstitial cells in the outer medulla. No areas of acute tubular necrosis were identified. The effect of this dose of cyclosporine on renal hemodynamics was examined in conscious restrained rats. Renal blood flow, measured by microsphere injection, was 70% of control after four daily doses and remained near this level after eight daily doses. The glomerular filtration rate, measured by iodothalamate clearance, was 70% of control after four doses but fell to 34% of control after eight doses. [3H]Thymidine incorporation into renal DNA was used as a sensitive index of renal cell proliferation after cyclosporine administration (100 mg/kg/day). [3H]Thymidine incorporation was increased over control 3-fold in the outer cortex, 7-fold in the inner cortex and 11-fold in the medullary-papillary regions of the kidney after eight daily doses of cyclosporine. Histoautoradiographic examination of renal sections revealed an increase in the number of labeled nuclei in all three regions of the kidney from rats treated with cyclosporine. Morphometric analysis demonstrated that the majority of proliferating cells were located in the interstitium and not in renal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic contrast agent-induced acute renal failure is an increasingly recognized clinical event. Multiple factors have been implicated in its development. Recent experiments have demonstrated that sodium diatrizoate, a common ionic radiocontrast agent, is moderately toxic to proximal tubule cells in vitro, and that this toxicity is enhanced by hypoxia. In this study, we compare toxicities of the nonionic radiocontrast agent, iopamidol, and the commonly used ionic contrast agent, diatrizoate. Suspensions enriched in proximal tubule segments were exposed for 82.5 min to 10 or 25 mM diatrizoate or 10 or 25 mM iopamidol with or without 22.5 min or 30 min of hypoxia. Cell viability parameters, including basal and uncoupled respiratory rates, tubule cell potassium and calcium levels and cell ATP content were measured. No consistent differences in tubule viability parameters were observed between tubule suspensions exposed to 10 mM concentrations of the radiocontrast agents during either oxygenated or hypoxic conditions. Under oxygenated conditions, both 25 mM iopamidol and diatrizoate exposure produced greater metabolic alterations in renal tubules than control conditions, but the effects were not statistically significant. With concomitant hypoxia, the alterations after 25 mM diatrizoate exposure were significantly greater than those seen after exposure to 25 mM iopamidol. Iopamidol had less of a detrimental effect on renal tubule potassium content and both basal and uncoupled respiratory rates than that of diatrizoate under these conditions. Thus, diatrizoate is more toxic to rabbit renal proximal tubule cells than iopamidol in vitro, and this difference in toxicity is enhanced by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)