Influence of the Timing of FK 506 (Tacrolimus) Administration on Recovery of Renal Function From Warm Ischemic Injury in Rats

Abstract

The influence of timing of FK 506 (Tacrolimus) administration on renal function and recovery from renal warm ischemia was studied in Sprague-Dawley rats. Animals were administered FK 506 and subjected to 60 min of renal warm ischemia by temporary occlusion of the renal artery and vein. No significant differences in serum creatinine levels among rats subjected to renal ischemia, FK 506, or FK 506 vehicle (methanol and 5% dextrose in water) were demonstrated. In contrast, FK 506 administration (4 mg/kg intraperitoneally) in combination with renal warm ischemia resulted in significant deterioration of renal function with peaking of serum creatinine on day 2. The timing of FK 506 administration relative to renal ischemia did not significantly affect serum creatinine levels. Rats that received FK 506 either 24 hr pre-ischemia, 4 hr pre-ischemia, 4 hr post-ischemia, or 24 hr post-ischemia all showed similar serum creatinine levels on day 2 (3.85 +/- 0.9, 4.7 +/- 0.5, 3.8 +/- 0.9, and 5.1 +/- 0.6 mg/dl, respectively, p = NS). In all animals, serum creatinine returned to baseline values by day 10. Histopathologic examination of kidneys revealed tubular atrophy and dilatation with tubular calcifications at the corticomedullary junction in FK 506 treated animals with or without ischemia. Our data suggest the timing of FK 506 administration in rats subjected to renal warm ischemia does not influence the extent of renal injury with an equally deleterious effect seen when administered within a 24 hr period of an ischemic event. Changes in kidney morphology, however, were seen in all FK 506 treated rats, with or without a period of warm ischemia.