- The effect of 45-min clamping of the renal artery was studied in the conscious uninephrectomized rat to reproduce the syndrome of hemodynamically mediated acute renal failure in humans after a single ischemic insult. Twenty-four hours after ischemia, creatinine clearance was reduced by 90%, whereas fractional excretion of sodium was markedly increased; over the subsequent 5 days, both values returned to normal. The animals were nonoliguric. Fractional clearances of graded sizes of neutral dextrans (radii 20-44 A), employed to detect transtubular backleak of inulin, were not significantly different 24 or 48 h postischemia from those in normal animals. The implication that the normal fractional dextran clearances excluded tubular backleak was tested directly by microinjecting [methoxy-3H]inulin into the proximal tubule. In most tubules injected, the recovery of radioactivity in the urine was markedly lower 24 and 48 h postischemia than that in normal rats; in a few injected tubules of postischemic kidneys, recovery was not different from that in normal animals. The low recovery of radioactive inulin was accounted for, at least in part, by transtubular backleak, as shown in experiments in which rats subjected to renal ischemia were cross-transfused with normal animals. These studies indicate that, despite the normal fractional dextran clearances, most tubules were severely injured as shown by tubule backleak of inulin.