Short-term immunosuppressive treatment of the donor ameliorates consequences of ischemia/ reperfusion injury and long-term graft function in renal allografts from older donors1

Reutzel‐Selke, Anja; Zschockelt, Thomas; Denecke, Christian; Bachmann, U.; Jurisch, Anke; Pratschke, Johann; Schmidbauer, G.; Volk, Hans‐Dieter; Neuhaus, P.; Tullius, Stefan G.

doi:10.1097/01.tp.0000063408.97289.89

Cited by 27 publications

(25 citation statements)

References 26 publications

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“…We found that there was no structure/function protection with EP therapy nor was the long-term increase in renal NADPH-dependent O 2 – production prevented. This contrasts to studies in ALLO (Fisher to Lewis) where function/structure is improved by short-term immunosuppressive/anti-inflammatory treatment of the donor [14]. Although individual agents used in this study have been shown to give short-term renoprotection (hours to 9 days) against I/R injury, their long-term effects are unclear.…”

Section: Discussioncontrasting

confidence: 46%

Lack of Long-Term Protective Effect of Antioxidant/Anti-Inflammatory Therapy in Transplant-Induced Ischemia/Reperfusion Injury

et al. 2006

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Background: Alloantigen-independent factors contribute to long-term damage in renal transplant recipients, likely due to ischemia/reperfusion (I/R) injury at transplantation (Tx). I/R injury promotes oxidative stress and inflammation resulting in endothelial injury. Methods: In this study we investigated the long-term efficacy (22 weeks) of short-term (10 day) endothelial protection therapy (EP) in ‘optimal’ donor kidneys using the male Fisher 344 rat isograft (ISO) model. ISO-EP kidneys were compared to untreated ISO (ISO-UN) kidneys. EP involved dexamethasone to donor, ex vivo treatment of the kidney with deferoxamine and tempol, and administration to the recipient of L-arginine and tempol for 10 days. Rats were sacrificed 22 weeks following Tx and compared to age-matched, normal controls. Results: Both groups of ISO Tx rats developed similar renal dysfunction and structural damage and renal NADPH-oxidase-dependent O₂^– production was similarly elevated in ISO-UN and ISO-EP groups vs. controls. In vitro renal cortex NO synthase (NOS) activity was also similar in ISO-UN and ISO-EP rats, despite lower nNOS and eNOS protein abundance in ISO-EP. Conclusion: I/R injury-induced late graft dysfunction occurs even when optimal donors are used and when short-term EP treatment is given. Increased renal superoxide production is not prevented by short-term EP therapy.

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Section: Discussioncontrasting

confidence: 46%

Lack of Long-Term Protective Effect of Antioxidant/Anti-Inflammatory Therapy in Transplant-Induced Ischemia/Reperfusion Injury

et al. 2006

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“…Acute tubular necrosis, assessed at 1 wk, was only seen in the 5-hr groups that had a similar degree of ischemic damage. Several successful strategies have been shown to protect kidneys against ischemic damage (10,(21)(22)(23). In the field of transplantation, as postischemic inflammatory insults boost the alloimmune response, regimens that interfere with host alloresponsiveness appear to be advantageous (8).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, a recent clinical study indicated that intraoperative Thymoglobulin administration, just before reperfusion, was associated with a significant reduction in the incidence of delayed graft function (DGF), possibly by decreasing ischemia-reperfusion injury (9). Another study showed that donor pretreatment with standard immunosuppressants improved long-term graft function and structure in ischemic rat renal allografts (10).…”

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confidence: 97%

Reduction of Postischemic Immune Inflammatory Response: An Effective Strategy for Attenuating Chronic Allograft Nephropathy

et al. 2005

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Strengthening initial immunosuppression attenuates the intensity and extent of the early postischemic immune-inflammatory response as well as later function and structure of renal allografts. Severe CAN may be prevented by reducing cold ischemia or strengthening immunosuppression. Because the former approach is not always possible, reinforcement of early immunosuppression constitutes an excellent alternative.

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“…Although interpretation of survival is a critical issue, and reports of survival rates following extended cold ischemia of kidneys can vary due to factors such as rat strains used and different surgical techniques [23,24] , variability was reduced in our setting, since all our surgical procedures were performed by one surgeon under standardized conditions. However, comparison to previously reported survival rates remains difficult since removal of the recipient's native right kidney is often not performed until several days after transplantation [24,25] , and in some rat kidney transplantation models that involve bilateral nephrectomy at the time of transplantation, observation periods for survival range from 24 h [26] to 2 weeks [27] .…”

Section: Discussionmentioning

confidence: 99%

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

Schmitz

Klawitter²,

Bendrick-Peart³

et al. 2006

Eur Surg Res

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Background: In kidney transplantation, preservation has a significant influence on organ function. Since previous reports have indicated a benefit of combining histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution, we evaluated the effects of initial flush with low viscosity HTK, followed by storage in UW. Material and Methods: Kidneys from inbred Lewis rats were procured using HTK or UW for initially perfusion and re-flushed after 30 min with either solution. In a third group, after perfusion with HTK, organs were re-flushed with UW. Organs were stored for 16–24 h (4°C). Study parameters were high-energy phosphates, histology, apoptosis, recipient survival and urine excretion of 15-F_2t-isoprostanes (oxidative stress marker). Results:Prior to transplantation, tissue ATP/ADP concentrations were: HTK/UW>UW-only >HTK-only. In transplanted kidneys, histological damage was highest after preservation in HTK-only. Twenty-four hours after transplantation (24 h cold ischemia time – CIT), cleaved-PARP was most abundant using UW-only. 16 h of CIT resulted in higher urine concentrations of isoprostanes in the order HTK-only (368 ± 308) > UW-only (157 ± 105) > HTK/UW (67 ± 26), and was lower in HTK/UW after 24 h of CIT (146 ± 38) vs. UW-only (507 ± 33 pg/mg creatinine). Survival (24 h CIT) was significantly reduced, and percentage of initial non-functioning (INF) kidneys highest in HTK-only (2.6 ± 0.3 days, 100%), compared to UW-only (13 ± 4.4 days, 75%) and HTK/UW (18.5 ± 4.6 days, 33%). Conclusions: In long-term preservation, UW is superior over HTK. However, our results indicate that perfusion with HTK prior to storage in UW may improve the results of UW alone which is reflected by better survival, lower rate of INF, higher cellular energy conservation and a decrease of free radicals.

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Short-term immunosuppressive treatment of the donor ameliorates consequences of ischemia/ reperfusion injury and long-term graft function in renal allografts from older donors1

Abstract: Donor treatment with approved immunosuppressants, in particular prednisolone or FK506, represents a novel therapeutic strategy of clinical relevance, most importantly when using grafts from marginal donors.

Cited by 27 publications

References 26 publications

Lack of Long-Term Protective Effect of Antioxidant/Anti-Inflammatory Therapy in Transplant-Induced Ischemia/Reperfusion Injury

Lack of Long-Term Protective Effect of Antioxidant/Anti-Inflammatory Therapy in Transplant-Induced Ischemia/Reperfusion Injury

Reduction of Postischemic Immune Inflammatory Response: An Effective Strategy for Attenuating Chronic Allograft Nephropathy

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

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