IMPROVEMENT OF RENAL PRESERVATION BY VERAPAMIL WITH 24-HOUR COLD PERFUSION IN THE ISOLATED RAT KIDNEY

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Abstract
There is substantial evidence that increased cellular calcium may activate processes that lead to cellular injury and death, and calcium entry blockers (CEB) have been shown to protect against renal ischemic injury. This approach has been used experimentally to enhance kidney preservation during both warm and cold ischemia. In the present study, the effect of the CEB verapamil on kidney function after 24 hr of hypothermic (4–7°C) perfusion was examined and compared with simple cold storage with Eurocollins' solution (4 hr), 4 or 24 hr cold perfusion, without the addition of verapmil. The cold perfusion media consisted of 3% albumin in phosphate-free Krebs-Henseleit saline supplemented with 5 mM glucose. Cold perfusion was performed at 40 mmHg perfusion pressure with either 0 (C) or 5 μM verapamil (V) added to the cold perfusion media. Renal functional parameters of plasma flow (RPF), inulin clearance (Cin), fractional (FRNa+) and net sodium reabsorption (TNa+) were assessed during 60 min of reperfusion at 37°C using 6.7% albumin in Krebs-Henseleit saline supplemented with glucose, inulin, and 20 amino acids. There was no increase in RPF with V (33±1 vs. 32±2 ml/min/g, NS) but Cin was significantly higher (271±30 vs. 168 ± 20 μl/min/g PNa+ (84±5 vs. 57±8%, P<.01), TNa+ (32±6 vs. 15±3 μmol/min/g, P<.01) and renal adenosine triphosphate (ATP) concentration (8.0±5 vs. 4.7±1.0 μmol/g dry tissue, P<.01). Thus, V appears not only to enhance kidney preservation with warm and cold ischemia but also improves renal function, as assessed by glomerular filtration rate (GFR) tubular function, and tissue ATP concentration with 24-hr cold perfusion.