Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.
Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012–2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A‐NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A‐NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49–67 years). Adjusted risk estimates were improved with A‐NRP for overall biliary complications (OR 0.300, 95% CI 0.197–0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042–0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267–0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373–0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001–1.007, p = .021) and re‐transplantation indication (HR 9.552, 95% CI 3.519–25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A‐NRP. While use of A‐NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.
The outcome was good, particularly in non-coinfected patients. Coinfected patients constitute an especially high-risk group for kidney transplantation.
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