Further evidence of tubular blockage after acute ischemic renal failure in Tupaia belangeri and rats

Abstract

1. Acute renal failure in man can best be simulated experimentally by using either temporary occlusion of the renal artery or perfusion of noradrenaline into the renal artery. 2. The kidney of Tupaia belangeri, a primitive primate, which may allegedly die from psychogenically induced renal failure, is surprisingly more resistant to temporary occlusion of the renal artery than that of the rat. 3. The results of physiological studies (measurements of intratubular pressures, proximal passage-times, inulin clearance) and the intravital microscopic appearances of the renal surface of the Tupaia kidney varied little from those of the rat. As intravital microscopic studies showed, however, only rarely are the distal tubuli visible on the surface of Tupaia kidneys, and stop-flow pressures measured in them proved remarkably high. 4. In Tupaia as in rats, anuria developing 48 hours after temporary ischemia is brought about by intratubular proteinaceous casts blocking the flow of urinary filtrate, most likely at Henle's loop. Both the diameter of the proximal tubular lumen and the intratubular pressures increase after temporary ischemia but the severity of the diuresis and inulin clearance decrease. To demonstrate that the proteinaceous casts block the tubular lumina, we have shown that when two micropipettes are inserted into the same nephron and that nephron is perfused, the intratubular pressure rises approaching systolic pressures. Renal failure becomes more severe the longer the duration of temporary ischemia (from 1 to 3 h). As renal damage progresses and intratubular pressures fail to rise, tubular permeability increases (leakage). 5. As with occlusion of the renal artery, infusion of the artery with noradrenaline leads to massive blockage of the nephrons by proteinaceous material in 48 h in the rat. Renal function (clearance of inulin, tubular passage times etc.) decreases as the infusion is prolonged (from 45 to 120 min), whereas the diameter of the tubular lumen and intratubular pressures increase. As studies with the double insertion of micropipettes and microperfusion have shown, tubular blockage by casts also occurs after perfusion of noradrenaline. Where the tubular damage is greatest, the tubules leak. 6. Histologically, the proteinaceous material blocking the urinary flow is primarily found near the loops of Henle. Depending on the degree of damage, we often observe increasing necrosis of tubules; that represents the morphological equivalent of changes in tubular permeability (leakage).