Improvement of Postischemic Kidney Function by Reperfusion With a Specifically Developed Solution (BT01)

Abstract

Reperfusion is a critical phase of organ preservation. The purpose of this study was to develop a solution specifically for postischemic kidney reperfusion. Unilateral left normothermic kidney ischemia was induced for 60 minutes in two groups of micropigs. In group 1 (control pigs, n = 6) the kidney was reperfused immediately with pure blood at systemic pressure by unclamping the renal artery. In group 2 (test animals, n = 6) the kidney was initially reperfused with an intracellular flush solution enriched with solution BT01 composed of cytoprotectors (natriuretic factor, PGI2), free radical chelating agents (allopurinol, mannitol), and substrates for the mitochondrial respiratory chain (aspartate, glutamate). This solution was mixed immediately before use with blood in a ration of 1:4 parts and injected into the left renal artery with a perfuser at a constant pressure of 60 mm Hg. After 20 minutes, the kidney was reperfused with systemic blood for 100 minutes. Glomerular filtration rate (GFR) was determined by measuring inulin clearance. Kidney blood flow was measured throughout the experiment. After 120 minutes of reperfusion, the kidneys were removed for histologic examination. In the control pigs (group 1) 50% of the animals were anuric. The ratio between GFR measured in the left kidney at the end of perfusion and at equilibrium in the remaining animals was 0.16 +/- 0.01. In test animals (group 2) all animals recovered diuresis. The ratio between GFR measured in the left kidney at the end of perfusion and equilibrium was 0.51 +/- 0.12 (p < 0.001, group 2 vs. group 1). In group 2 postperfusion kidney blood flow was higher than in group 1 (63.0 ml/min vs. 27.4 ml/min; p < 0.05) because of a decrease in renal vascular resistance. Light microscopic examination of kidneys form animals in group 1 revealed tubular necrosis that extended to the parenchyma, with exposure of tubular interstitium. In group 2 only degenerative lesions with edema of tubular cells and disappearance of brush borders were observed. Our findings indicate that flushing the kidneys with BT01 solution mixed with blood improves postischemic kidney function by reducing reperfusion damage.