Superficial Nephron Obstruction and Medullary Congestion after Ischemic Injury: Effect of Protective Treatments

Abstract

90 min of renal artery occlusion in previously unilaterally nephrectomized rats produce acute renal failure (ARF) (plasma creatinine at 48 h after ischemia: 636 +/- 44 vs. 133 +/- 9 mumol/l in controls). Between 1 and 48 h after releasing the occlusion, two populations of superficial nephrons could be observed, one with dilated tubules and elevated proximal tubular pressures (PTP: 39 +/- 1 vs. 12 +/- 1 mm Hg in controls) and the other with collapsed tubules and decreased PTP (9 +/- 1 mm Hg). Proximal tubular passage time (PPT) could not be determined with the Lissamine green technique. Seven methods of pretreatment were tested, 5 of which provided partial functional protection (DOCA/NaCl/NaCl, furosemide infusion, inosine bolus, mannitol bolus and the combination of the last two). Neither renal renin levels nor urinary NaCl excretion were consistently correlated with protection. Functionally protected rats consistently showed no PTP increase and normal PPT in the tubules at the kidney surface. However, plasma creatinine at 48 h differed markedly within the 5 protected groups, ranging from 168 +/- 18 to 398 +/- 35 mumol/l. Extensive medullary congestion was seen at 1-6 h after ischemia only in those rats with obstructed, high pressure nephrons at the kidney surface. To conclude: (1) Functional protection from ischemic ARF, both with and without an accompanying increase in solute excretion, was achieved by the abolition of tubular obstruction. (2) Despite similar degrees of restoration of superficial nephron function, the persisting impairment of whole kidney function differed markedly between the protected groups. (3) Impairment of deeper nephron function must therefore play a major role, perhaps through persisting obstruction in the long loops of Henle. (4) High pressure nephrons may compromise medullary venous outflow in the outer zone of the outer medulla.