Kidney preservation with IGL-1 solution: a preliminary report.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys.

A primate model of renal ischemia-reperfusion injury for preclinical evaluation of the antileukocyte function associated antigen 1 monoclonal antibody odulimonab.

PURPOSE: We established a primate model to investigate the effects of the antileukocyte function associated antigen 1 (CD 11a) mAb odulimomab (Imtix-Sangstad, Lyon, France) for preventing renal ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 34 Macaca cynomolgus monkeys into groups 1 and 2, which received a renal autograft after 2 hours of cold ischemia, and groups 3 and 4, which received the autograft after 24 hours of cold ischemia. Before cold ischemia all harvested kidneys were subjected to 30 to 45 minutes of warm ischemia. Groups 1 and 3 monkeys were treated with an antileukocyte function associated antigen 1 mAb before cold ischemia and then for 3 days, while groups 2 and 4 monkeys received an IgG1 isotype control. In all groups renal function was investigated before warm ischemia and 72 hours after reperfusion. Serum creatinine and the leukocyte count were determined daily. Histological studies were done and lactoferrin was measured in the autotransplanted kidney 72 hours after reperfusion. RESULTS: A decrease in renal function was shown after 2 hours of cold ischemia with tubular necrosis and mild cell infiltration, while after 24 hours of cold ischemia there was severe renal failure with tubular and glomerular necrosis, and leukocyte infiltration. A significant improvement in renal function and decrease in kidney lactoferrin content was evident in group 1 compared to group 2 at 72 hours, while no significant difference was noted in groups 3 and 4. No difference in histological patterns was evident in treated and untreated animals. CONCLUSIONS: This study provides evidence for the validity of this ischemia-reperfusion injury model in primates. The protective effects of antileukocyte function associated antigen 1 mAb on renal injury was not as dramatic as in rodent models but a significant improvement in renal function was observed in treated animals after 2 hours of cold ischemia.

Evaluation of parenchymal and nonparenchymal cell injury after different conditions of storage and reperfusion.

We used the isolated perfused rat liver model (IPRL) to assess parenchymal and nonparenchymal cell integrity after different conditions of storage and reperfusion. Two studies were performed. In study 1, the IPRL was applied to evaluate the effects of 30 min of normothermic reperfusion with Elohes solution, enriched William's medium (Wif), or Carolina rinse solution (CRS) following 24 h of cold preservation in high-K+ or high-Na+ UW solution. As indicated by creatine kinase-BB (CK-BB) release, reperfusion with CRS provided greater protection of endothelial cells after storage in high-K+ UW solution than after storage in high-Na+ UW solution. In study 2, livers were cold-preserved (24 h, 4 degrees C) in either high-K+ or high-Na+ UW solution, then flushed with either CRS or Wif solution at room temperature before reperfusion (120 min, 37 degrees C) with 5% albumin-William's medium E. There was no statistical difference between the rinse solutions for bile flow and transaminases release. However, CRS improved bile indocyanine green excretion, which is known to be a marker of parenchymal and nonparenchymal cell integrity. Therefore, we can assume that this rinse solution protects rat liver grafts from reperfusion-induced microvascular damage.

High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat liver graft.

The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K+ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na+ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na+ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na+ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na+ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K+ UW solution. Liver preservation in the high-Na+ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution.

Nifedipine improves recovery function of kidneys preserved in a high-sodium, low-potassium cold-storage solution: study with the isolated perfused rat kidney technique.

BACKGROUND: Extracellular types (high-Na) of cold-storage solution (CSS) have been shown to be more effective in preserving kidneys than intracellular CSS (high-K). On the other hand, calcium entry blockers (CEB) have been demonstrated to improve graft function when administered after and/or prior to transplantation. The ischaemia reperfusion syndrome involves, in part, an alteration in intracellular calcium metabolism that induces an increase in renal vascular resistances (RVR) and other cellular dysfunction, and high-K CSS per se are vasoconstrictive. Since CEB act via a modification in intracellular calcium metabolism on vascular smooth muscle, glomerular, and tubular cells, we evaluated the actual benefit on CEB on kidneys preserved in Belzer's CSS (K-UW) and a high-Na version of Belzer's CSS (Na-UW). METHOD: The isolated perfused rat kidney (IPK) was used, first as a vascular bed to test the effects of CSS on RVR, and the influence of nifedipine. Second, the recovery function of the IPK was assessed by GFR and tubular Na reabsorption, after 24 h preservation in K-UW and Na-UW, with or without nifedipine. Results were compared with a control group in which renal function was measured without prior cold-storage. RESULTS: K-UW but not Na-UW induced an increase in RVR when flushed into the kidney. This vasoconstriction is prevented by nifedipine. K-UW CSS was more deleterious to renal function than Na-UW. Addition of nifedipine to the flush, the CSS for 24 h, and to the normothermic reperfusate further improved recovery function of the IPK cold stored in Na-UW but not in K-UW, without any modification of RVR. CONCLUSION: Nifedipine may be of potential effect in attenuating ischaemic injury by a mechanism which does not involve its vasodilatory properties.