Impact of Organ Preservation Using HTK for Graft Flush and Subsequent Storage in UW in Rat Kidney Transplantation

Schmitz, Volker; Klawitter, Jost; Bendrick-Peart, Jamie; Haschke, Manuel; Beckey, Virginia E.; Laudi, Sven; Neumann, Ulf; Schoening, Wenzel; Neuhaus, P.; Christians, Uwe; Puhl, Gero

doi:10.1159/000094600

Cited by 28 publications

(13 citation statements)

References 70 publications

(27 reference statements)

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“…Its sensitivity and specificity may be affected mainly by sample processing which we tried to overcome by appropriate pretreatment of the sample including microwave irradiation at basic pH values [35] . In general, the rate of apoptosis was similar to that reported by other researchers who studied renal preservation with the UW solution as we did [32,36] . Surprisingly, we nearly found no apoptotic cells in the glomeruli, which were simultaneously stained by fluorescent antibodies against podocalyxin-like protein 1 for better identification ( fig.…”

Section: Discussionsupporting

confidence: 90%

“…Other authors using the storage in the UW solution as a standard method usually performed only a unilateral nephrectomy before transplantation which enabled them to investigate the morphology and dynamics of the reparatory process but precluded them from following the onset and early evolution of the graft function [30,31] . In a paper by Schmitz et al [32] , comparable results were reported in a study arm with 24 h cold storage in the UW solution and pretransplant bilateral nephrectomy.…”

Section: Discussionmentioning

confidence: 53%

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Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia

Marada

Zacharovová²,

Saudek³

2010

Eur Surg Res

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Background: The two-layer organ preservation method (TLM) based on oxygenated perfluorocarbon overlaid with University of Wisconsin (UW) solution has been successfully used in clinical islet and experimental heart and intestine transplantation. We tested whether this technique would prevent tissue damage and improve kidney function in a model of syngeneic kidney transplantation with prolonged ischemia time. Methods: Kidneys were stored for 24 h either in UW solution (n = 16), with TLM (n = 16) or transplanted immediately (control group, n = 12). In half of the animals, survival was observed and in the other animals grafts were procured for semiquantitative histological scoring and TUNEL apoptosis assessment 24 h after transplantation. Results: One-month survival rates in the UW, TLM and control groups were 12.5, 62.5 and 100%, respectively (UW vs. TLM, p < 0.01). Median creatinine levels 24 h after transplantation were 381, 299 and 121 µM, respectively (UW vs. TLM, p < 0.02). Histological scoring showed more severe tissue damage in the UW group than in the TLM group (p < 0.05). Apoptosis was more frequent in the UW group than in the TLM group (p < 0.05). Conclusion: We demonstrated for the first time that conservation with TLM significantly improves the outcome of kidney transplantation in a rat model and should therefore be further studied in larger animals.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 53%

Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia

Marada

Zacharovová²,

Saudek³

2010

Eur Surg Res

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“…A previous study also suggested that the enhancement of cyclosporine toxicity by sirolimus is mediated by an increase in reactive oxygen species and subsequently a decrease in mitochondrial energy metabolism [34]. We have also shown that isoprostane concentrations in urine after transplantation reflect ischemia/reperfusion damage after cold ischemia and transplantation [35]. Isoprostanes are reliable in vivo markers of oxidative stress [36].…”

Section: Discussionmentioning

confidence: 80%

Metabolic Profiles in Urine Reflect Nephrotoxicity of Sirolimus and Cyclosporine following Rat Kidney Transplantation

Schmitz

Klawitter

Bendrick-Peart³

et al. 2009

Nephron Exp Nephrol

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Background: Cyclosporine and/or sirolimus impair recovery of renal transplants. This study examines the changes in urine metabolite profiles as surrogate markers of renal cell metabolism and function after cyclosporine and/or sirolimus treatment employing a rat kidney transplantation model. Methods: Using inbred Lewis rats, kidneys were transplanted into bilaterally nephrectomized recipients followed by treatment with either CsA (cyclosporine) 10, Rapa (sirolimus) 1, CsA10/Rapa1 or CsA25/Rapa1 mg/kg/day for 7 days. On day 7, urine was analyzed by ¹H-NMR spectroscopy. Blood and kidney tissue drug concentrations, tissue high-energy compounds (including ATP, ADP) and oxidative stress markers (15-F_2t-isoprostanes) in urine were measured by HPLC mass spectrometry. Results: Changes in urine metabolites followed the order Rapa1 < CsA10 < CsA10/Rapa1 < CsA25/Rapa1. Compared with controls, CsA25/Rapa1 showed the greatest changes (creatinine –36%, succinate –57%, citrate –89%, α-ketoglutarate –75%, creatine +498%, trimethylamine +210% and taurine +370%). 15-F_2t-isoprostane concentrations in urine increased in the combined immunosuppressant-treated animals ([CsA25/Rapa1]: 795 ± 222, [CsA10/Rapa1]: 475 ± 233 pg/mg/creatinine) as compared with controls (165 ± 78 pg/mg creatinine). Rapa concentration in blood and tissues increased in the combined treatment (blood: 31 ± 8 ng/ml, tissue: 1.3 ± 0.4 ng/mg) as compared with monotherapy (blood: 14 ± 8 ng/ml, tissue: 0.35 ± 0.15 ng/mg). Drug blood concentrations correlated with isoprostane urine concentrations, which correlated negatively with citrate, α-ketoglutarate and creatinine concentrations in urine. Only CsA25/Rapa1 significantly reduced high-energy metabolite concentrations in transplant kidney tissue (ATP –55%, ADP –24%). Conclusion: Immunosuppressant drugs induce changes in urine metabolite patterns, suggesting that immunosuppressant-induced oxidative stress is an early event in the development of nephrotoxicity. Urine 15-F_2t-isoprostane concentrations and metabolite profiles may be sensitive markers of immunosuppressant-induced nephrotoxicity.

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“…The beneficial effects of all components of the UWS and HTK well-tested preservation solutions have been extensively reviewed before in the literature [41,42] and are not the prime target of this publication. In this work, we particularly emphasize the main qualities of the new components introduced in the HBS solution and determine the physiological and biochemical comparative analysis of HBS, UWS, and HTK preparations.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Novel Cold Storage Solution (HBS) in a Rat Kidney Transplant Model

López-Neblina¹,

Toledo

Toledo‐Pereyra

2007

Journal of Investigative Surgery

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We developed an improved solution for hypothermic storage (0-4 degrees C) of kidneys. The cold storage solution (HBS) was composed of macromolecules, high-energy cellular substrates, and a mixture of antiproteolytic amino acids, antioxidants, and anti-inflammatory compounds. The objectives in developing this solution were to achieve superior metabolic support of the kidney during cold storage and to protect against ischemic injury. Inbred Brown Norway rats, weighing 225-250 g, were subjected to orthotopic ultrarapid technique for kidney isotransplantation to minimize warm ischemia and to test the preservation process. The kidney was transplanted after 12 h of preservation. The animals were divided into three groups based upon the preservation solution utilized: HBS solution, HTK solution (Custodiol), and UW solution (UWS)(ViaSpan). Among the recipients, each group had two subsets. The first subset of animals was used to assess survival at 7 days as well as the reperfusion damage index (RDI) based on the macroscopic physical characteristics of the kidney at the time of transplantation. The second subset in each group was utilized to measure serum creatinine and blood urea nitrogen at 4 and 7 days, and histology at death or sacrifice. Mean +/- standard deviation (M +/- SD) was used for all parameters studied. The HBS solution showed significantly better protection at 12 h when compared to HTK and UW solutions. The reperfusion damage index (RDI) showed excellent preservation in the HBS (14 +/- 1), good preservation in UWS (13 +/- 1.5), and moderate preservation in the HTK (11 +/- 2) group. Histology was in concordance with the RDI, showing better histological findings with HBS and UW solutions than with the HTK group. Serum creatinine was significantly better in the HBS group when compared to HTK and UWS. Survival was statistically different, with 80% survival at 7 days in the HBS group, 20% survival in the HTK group, and 50% survival in the UWS group (p < .05). The HBS solution offered a new alternative for kidney cold storage with significantly better results when compared to the current gold standards of HTK and UW solutions in Brown Norway rats. This solution warrants further testing in other mammals.

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Impact of Organ Preservation Using HTK for Graft Flush and Subsequent Storage in UW in Rat Kidney Transplantation

Cited by 28 publications

References 70 publications

Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia

Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia

Metabolic Profiles in Urine Reflect Nephrotoxicity of Sirolimus and Cyclosporine following Rat Kidney Transplantation

Evaluation of a Novel Cold Storage Solution (HBS) in a Rat Kidney Transplant Model

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