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Background: Further expansion of the donor pool with ischemically damaged kidneys will be predicated on the ability to develop prognostic testing. Using a well-established canine autotransplantation injury model, we assessed whether actual restoration of renal metabolism by ex vivo warm perfusion could be used to predict the status of an organ before transplantation., Methods: Kidneys were subjected to 30 min of warm ischemia followed by 24 hr of static storage in ViaSpan at 4 degrees C. After warm ischemia and static storage the kidneys were transitioned to 3 hr of warm perfusion using Exsanguinous Metabolic Support technology. During this period, parameters indicative of renal metabolism and vascular function were used to predict outcomes prospectively. Parameters included measures of oxidative metabolism, perfusion characteristics, and vascular condition. A Viability Score (VS) was calculated as the sum of the three parameters mentioned above. Results were grouped by a VS>2 and a VS<2., Results: A clear association between the severity and duration of graft dysfunction and the VS was observed. Organs with a VS>2 had a significantly milder period of acute tubular necrosis, with both a less severe rise in serum creatinine (mean of 4.4 vs. 11 mg/dl) and a shorter recovery period (mean of 8 vs. 18 days) than those with a VS<2., Conclusions: Results indicate the possibility of utilizing warm perfusion to evaluate kidneys before transplantation. The VS developed demonstrated efficacy in classifying the severity of the acute tubular necrosis and the occurrence of primary nonfunction, offering a sensitive assay for prospective organ testing.

Background: The compounding damage of warm ischemia (WI) followed by cold preservation is a major barrier in renal transplantation. Although the relative effect of WI is not yet well understood, therapeutic strategies have mostly focused on minimizing the pathology seen upon reperfusion from the cold. Our study was designed to examine the effect of restoration of renal metabolism by warm perfusion on graft survival and to investigate the compounding damage of WI., Methods: Using a known critical canine autotransplantation model (1), kidneys were exposed to 30 min WI followed by 24 hr cold storage in Viaspan. They were then either reimplanted directly or first transitioned to 3 hr of warm perfusion with an acellular perfusate before reimplantation. Contralateral kidneys were subjected to 0, 30, or 60 min WI; 24 hr cold storage, and 3 hr warm perfusion., Results: Transplanted kidneys that were warm perfused before reimplantation had both lower 24 hr posttransplant serum creatinine (median of 3.2 vs. 4.1 mg/dl) and lower peak serum creatinine (median of 4.95 vs. 7.1 mg/dl). Survival rate for warm perfused kidneys was 90% (9/10) vs. 73% (8/11). In the contralateral kidneys, metabolism was affected by the compounding damage of WI. Renal oxygen and glucose consumption diminished significantly, whereas vascular resistance and lactate dehydrogenase-release rose significantly with increasing WI., Conclusions: The results demonstrate a reduction of reperfusion damage by an acellular ex vivo restoration of renal metabolism. Furthermore, data from the contralateral kidneys substantiates the relative role of WI on metabolism in renal transplantation.

The current shortage of transplantable organs has renewed interest in kidneys obtained from non-heart-beating donors. Kidneys from these donors have suffered warm ischemia (WI). The effectiveness of two preservation solutions, i.e., the University of Wisconsin (UW) and the histidine tryptophan ketoglutarate (HTK) solutions, for preservation of kidneys that have been subjected to WI was tested in dogs. The left kidney was autotransplanted after 30 min of WI, and subsequent 24-hr cold storage (CS) in either UW (n = 6) or HTK (n = 6), with immediate contralateral nephrectomy. Surgical biopsies from the cortex were taken before WI, after 30 min of WI, after 24 hr of CS, and after 1 hr of reperfusion for electron microscopy and for analysis of energy metabolites. At 2 weeks after transplantation in the UW group, 4 out of 6 and, in the HTK group, 1 out of 6 dogs survived. As from day 2, serum creatinine was lower in the UW group as compared with the HTK group (P < 0.05). After 24 hr of CS, in the HTK group the luminal membranes of proximal tubular cells were partly denuded of microvilli. Moreover, the tubular lumen was filled with blebs and debris. In the UW group, the brush borders remained intact, although microvilli were swollen. Energy metabolites were analyzed with HPLC. Thirty minutes of WI resulted in a +/- 45% reduction of total adenine nucleotide (TAN) content. During CS, TAN levels further decreased in both groups; however, after 24 hr of CS, the levels of adenosine, inosine, hypoxanthine, and xanthine were significantly higher in the UW group as compared with the HTK group (P < 0.05, P < 0.01, P < 0.01, P < 0.01). At 1 hr of reperfusion, TAN levels were higher in the UW group as compared with the HTK group (4.66 +/- 0.16 vs. 4.02 +/- 0.28, P < 0.05). Our results show that UW is a superior solution compared with HTK in the preservation of ischemically damaged kidneys, demonstrating better survival, better recovery of kidney function, better protection against ischemia-induced ultrastructural damage, and better preservation of energy metabolism indicated by (a faster) regeneration of TAN levels after reperfusion.