Mechanisms in acute oliguric renal failure induced by tetracycline infusion

Tetracycline hydrochloride (TC), 30-70 mg/kg infused intravenously in dogs in the course of a few minutes, reduced clearance of inulin (Cin) and p-aminohippuric acid (CPAH) on an average to less than 5% of control. In spite of increased intrarenal pressure (approximately 50 mm Hg), electromagnetically recorded renal blood flow was preserved, indicating that the reduction of Cin and CPAH resulted from tubular obstruction, not renal vasoconstriction. The metabolic rate of the cortex and outer medulla fell to 69% of control after TC, as measured by the heat accumulation rate. Further reduction to basal metabolic level (30% of control) was reversibly produced by elevating ureteral pressure, suggesting that the high metabolic rate was caused by continued active reabsorption of sodium chloride at about half the control rate. Thus Cin greatly underestimated glomerular filtration rate in the TC-damaged kidney. From these results and the observation of TC-containing casts in the medullary tubules, we conclude that TC caused tubular obstruction and that leakage of inulin and PAH from the tubules occurred mainly distally to the major sodium-reabsorbing tubular segments.