Na-K/2Cl transporter inhibition for reduction of postischemic kidney failure tested in autologous reperfusion.

Postischemic kidney function may be influenced by donor conditioning. The sulfamoyl-benzoate "piretanide" (P) is a diuretic agent with an inhibitory effect on the luminal Na-K-2CL-transporter system in the ascending part of the loop of Henle. A clinical pilot study demonstrated a lower rate of organ dysfunction following transplantation in humans when the donor organs were pretreated with piretanide. In an experimental ex vivo model the effect of piretanide on immediate organ function following long or short cold ischemia was studied. Porcine kidneys (n = 36) were removed after in situ transaortal hypothermic flushing with 21 Eurocollins solution. Following short storage (1 h, n = 18) or long storage (24 h, n = 18) the kidneys were reperfused with intraoperatively drawn heparinized autologous blood diluted with Ringer's lactate to a hematocrit of 25%. Urine flow was higher in the piretanide-pretreated group (p), especially after long storage. The electrolyte loss was comparable in both groups. Postischemic endogenous creatinine clearance was significantly elevated in the treatment group (4.45 +/- 0.6 ml/min per 100 mg in P vs 1.91 +/- 0.4 ml/min per 100 mg, in control, P < 0.05 Mann-Whitney test). Renal hemodynamics were improved by piretanide, resulting in significantly lower resistance and allowing higher flow during pressure-controlled perfusion. O2 consumption, representing general metabolic activity, was higher after long storage, indicating an earlier recovery from cold ischemia. In this ex vivo model, autologous reperfusion of porcine kidneys could be improved by piretanide pretreatment. Autoregulation of kidney vasculature was maintained as well as functional parameters such as creatinine clearance or gluconeogenesis. Therefore, piretanide may be used in larger clinical trials to further improve organ quality in times of donor shortage.