Outcomes and factors leading to graft failure in kidney transplants from deceased donors with acute kidney injury—A retrospective cohort study

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.

Assessment of risk factors for hospital readmission after kidney transplantation

Background and Purpose: Hospital readmission after kidney transplantation is a real challenge for both patients and healthcare systems. Assessment of the risk factors of readmission after kidney transplantation is vital and can reduce morbidity and cost in transplant recipients and donors. The aim of the current study was to determine the risk factors of hospital readmission in patients undergoing kidney transplantation in Montaserieh Hospital of Mashhad, northeast of Iran. Materials and Methods: This retrospective study included 523 first kidney transplant patients between January 2013 and March 2019 from the Montaserieh Hospital Information System (HIS) of Mashhad, Iran. Every-time readmission was the study primary outcome. Donors and recipient's demographic data, recipient's comorbidities, reasons for end-stage renal disease (ESRD), panel reactive antibody (PRA) status, dialysis parameters, cold ischemic time, and delayed graft function (DGF) were the potential risk factors. Statistical analysis was done using Chi-square and Student's t-test. Results: Data from 523 patients were assessed for potential eligibility. Based on the exclusion criteria, data from 479 patients were included in the final analysis. 174 (36.3%) patients were never readmitted, and 305 (63.7%) were readmitted at least once post-discharge. 39 (12.8%) were readmitted within the first-month post-discharge. Older age, sex, higher prevalence of comorbidities, diabetes and hypertension, duration of primary disease before transplantation, hemodialysis and duration of pre-transplant dialysis, mean pre-transplant platelet count, intraoperative complications, increased cold ischemic time, and delayed graft function were associated with a higher prevalence of readmission (p<0.05). Conclusion Our results showed that different independent variables and patients' comorbidities were important risk factors for readmission after kidney transplantation. Early prediction of these risk factors could result in prevention from readmission in patients undergoing kidney transplantation.

Kidney transplant outcomes after medical assistance in dying

Introduction: After nearly four years of Canadian experience with medical assistance in dying (MAiD), the clinical volume of organ transplantation following MAiD remains low. This is the first Canadian report evaluating recipient outcomes from kidney transplantation following MAiD. Methods: This was a retrospective review of the first nine cases of kidney transplants following MAiD at a Canadian transplant center. Results: Nine patients underwent MAiD followed by kidney retrieval during the study period. Their diagnoses were largely neuromuscular diseases. The mean warm ischemic time was 20 minutes (standard deviation [SD] 7). The nine recipients had a mean age of 60 (SD 19.7). The mean cold ischemic time was 525 minutes (SD 126). Delayed graft function occurred in only one patient out of nine. The mean 30-day creatinine was 124 umol/L (SD 52) . The mean three-month creatinine was 115 umol/L (SD 29). Conclusions: We report nine cases of kidney transplantation following MAiD. The process minimized warm ischemia, resulting in low delayed graft function rates, and acceptable post-transplant outcomes. Further large-scale research is necessary to optimize processes and outcomes in this novel clinical pathway.

Predictors of CMV Infection in CMV-seropositive Kidney Transplant Recipients: Impact of Pre-transplant CMV-specific Humoral Immunity

Introduction Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a relatively lower risk of CMV infection than CMV-seronegative recipients who receive allograft from CMV-seropositive donors, some patients remain at risk of CMV infection after transplant. We investigated the pre-transplant CMV-specific humoral immunity (CHI) and other CMV infection predictors in CMV-seropositive kidney transplant (KT) recipients. Methods This retrospective study was conducted on adult CMV-seropositive KT recipients during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. CHI, measured with an enzyme-linked fluorescent immunoassay and other predictors for CMV infection, was analyzed using Cox proportional hazards models. Results Of the 340 CMV-seropositive KT recipients (37% female; age [mean ± SD]: 43±11 years), 69% received deceased-donor allograft and 64% received induction therapy. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%. In multivariate analysis, low pre-transplant CHI (defined as anti-CMV IgG titer &lt;20 AU/ml) was significantly associated with CMV infection (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant predictors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]). Conclusion A low pre-transplant CHI is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. A quantitative anti-CMV IgG assay could potentially stratify CMV-seropositive patients at risk of CMV infection after KT.

Systematic Assessment of Safety Threshold for Donor Age in Cadaveric Liver Transplantation

Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature.Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model.Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P &gt; 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P &lt; 0.05). A spline model showed that transplants using grafts from donors &lt;43 years old were not associated with age-related risks (P &gt; 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P &lt; 0.05).Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.

Transcriptomic investigation reveals donor specific gene signatures in human lung transplants

RationaleTransplantation of lungs from donation after circulatory death (DCD) in addition to donation after brain death (DBD) became routine worldwide to address the global organ shortage. The development of ex vivo lung perfusion (EVLP) for donor lung assessment and repair contributed to the increased use of DCD lungs. We hypothesise that better understanding of the differences between lungs from DBD and DCD donors, and between EVLP and directly transplanted (non-EVLP) lungs, will lead to discovery of the injury specific targets for donor lung repair and reconditioning.MethodsTissue biopsies from human DBD (n=177) and DCD (n=65) donor lungs assessed with or without EVLP, were collected at the end of cold ischemic time. All samples were processed with microarray assay. Gene expression, network and pathway analyses were performed using R, Ingenuity Pathway Analysis and STRING. Results were validated with protein assay, multiple logistic regression and 10-fold cross validation.ResultsOur analyses showed that lungs from DBD donors have up-regulation of inflammatory cytokines and pathways. In contrast, DCD lungs display a transcriptome signature of pathways associated with cell death, apoptosis and necrosis. Network centrality revealed specific drug targets to rehabilitate the DBD lungs. Moreover, in DBD lungs, TNFR1/2 signalling pathways and macrophage migration inhibitory factor associated pathways were activated in the EVLP group. A panel of genes that differentiate the EVLP from non-EVLP group in DBD lungs was identified.ConclusionThe examination of gene expression profiling indicates that DBD and DCD lungs have distinguishable biological transcriptome signatures.