Kidney Recipients Research Articles

Treatments for pathogen infection rescued 2 patients with renal artery rupture after kidney transplantation: A case report.

Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death. Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery. The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens. The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days). The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19. In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue.

Norovirus Management and Outcomes in a Multicenter Pediatric Kidney Transplant Population.

Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2-11.2 years), and median time post-transplant was 1.9 years (IQR 0.8-3.8 years). Median diarrheal duration was 16 days (IQR 6.0-41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty-one (53%) patients developed acute kidney injury. Thirty-five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: -17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment.

The effect of remote ischemic conditioning on mortality after kidney transplantation: the systematic review and meta-analysis of randomized controlled trials

BackgroundIschemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes.MethodsResearchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1.ResultsOut of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13–75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14–3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23–1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30–1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73–1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61–1.56, P = 0.93).ConclusionsIt could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future.Systematic review registrationPROSPERO CRD42022336565.

Renal cell carcinoma in a transplanted kidney: a retrospective evaluation

IntroductionKidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48–82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10–30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature.ObjectiveTo determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development.Materials and methodsA retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm.ResultsThe incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient.ConclusionLaparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease.

Revolutionizing Organ Transplantation With Robotic Surgery.

The aim of this study was to evaluate the impact of robotic techniques on organ transplantation outcomes. The evolution of organ transplantation is becoming influenced by the adoption of minimally invasive techniques, transitioning from laparoscopic to robotic methods. Robotic surgery has emerged as a significant advancement, providing superior precision and outcomes compared with traditional approaches. This perspective includes a systematic review of the literature, original data from a high-volume center, as well as an international survey focusing on perceptions related to robotic versus laparoscopic and open approaches. The systematic review and meta-analysis revealed lower morbidity with robotic donor nephrectomy, recipient kidney transplant and donor hepatectomy. Our center's experience, with over 3000 minimally invasive transplant procedures (kidney, liver, donor, and recipient), supports the superiority of robotic transplant surgery (RTS). The global survey confirms this shift, revealing a preference for robotic approaches due to their reduced morbidity, despite challenges such as access to the robotic system and cost. This comprehensive overview including a systematic review, original data, and perceptions derived from the international survey demonstrate the superiority of robotic transplant surgery (RTS) across a range of organ transplantations, for both donors and recipients. The future of RTS depends on the efforts of the surgical community in addressing challenges such as economic implications, the need for specialized surgical training for numerous surgeons, as well as wide access to robotic systems worldwide.

The SElf-Care After REnal Transplantation Study: A Retrospective Evaluation of a Home-Monitoring Program Implemented as Standard Care.

After transplantation self-management is essential for graft survival and optimal quality of life. To address the need for home-based support in self-management, we implemented the "SelfCare after Renal Transplantation" (SeCReT) box, containing home-monitoring equipment combined with a smartphone application that was linked to the electronic patient records. This study investigated the uptake and continuation, protocol adherence, and subjective evaluation of this home-monitoring program. All "de novo" kidney recipients who received the SeCReT-box in the study period (Aug 2021-Dec 2022) were eligible for inclusion. Protocol adherence was defined as ≥75%. Subjective evaluation was assessed with a 5-item questionnaire. Of the 297 recipients transplanted, 178 participants (60%) were included in the analysis. Protocol adherence was 83%, 73%, 66%, and 57% respectively at 5, 10, 20, and 40weeks of the protocol. With regard to continuation, 135 participants were still in the program at the end of the study period (75% retention rate). Regarding subjective evaluations, 82% evaluated the program positively, and 52% reported lower care needs due to home-monitoring. Results are positive among those who entered and continued the program. Qualitative research is needed on barriers to entering the program and facilitators of use in order to promote optimal implementation.

SARS-CoV-2 Vaccination Rates and Uptake of Tixagevimab-Cilgavimab Among a Cohort of Pediatric Solid Organ Transplant Recipients.

There is a lack of data regarding SARS-CoV-2 vaccination rates and tixagevimab-cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates. We reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS-CoV-2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS-CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months. Our study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS-CoV-2 vaccines. Sixty-eight (61.8%) patients received at least one vaccine. This varied by age group, with f of≥12 years olds, 40.9% of 5-11 year olds and 14.3% of under 5 year olds (p=0.001). Seven patients (6.4%) were up-to-date (UTD) for age. There was no difference in UTD status by organ type (p=0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p=0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p=0.158) or whether they saw ID (p=0.273). Despite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS-CoV-2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS-CoV-2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Mechanical Preservation and Delayed Graft Function and Hospital Length of Stay as Deployed in the United States: Analysis of the Last Decade.

BACKGROUND Mechanical preservation (MP) of deceased donor kidney transplants showed a 30% to 50% reduction in delayed graft function (DGF) as defined by dialysis in the first week, when compared with cold storage. DGF is associated with longer hospital stays and increased costs. In this study, we sought to understand the impact of MP on rates of DGF and length of hospital stays in a contemporary cohort of deceased donor kidney transplants in the United States. MATERIAL AND METHODS All single deceased donor kidney transplants performed between January 1, 2010, and September 2, 2020, were identified in the Scientific Registry of Transplant Recipients database. Donor kidneys were considered pumped if the transplant center received the kidney on the pump. RESULTS Multivariate logistic regression showed that MP had similar odds of reduction of DGF for all subsets of donors. The unadjusted rate of DGF for pumped brain-dead standard criteria donor (BDSCD) recipients was similar to that of donors stored on ice. The rate of DGF for expanded criteria donors (ECD) and donors after cardiac death (DCD) was lower in the recipients who received MP. The similar DGF rates in BDSCD donor recipients were due to longer cold ischemia times in MP kidneys. The lower DGF rates seen in ECD and DCD recipients of pumped kidneys did not translate into a shortened length of hospitalization after transplant. CONCLUSIONS As currently deployed, only DCD and ECD donor recipients of MP kidneys experienced a lower DGF rate. In all subsets of patients, MP did not appreciably shorten the hospital length of stay.

Late Onset of Renal Abscess Mimicking Malignancy in a Retransplant Female

Abstract A 67-year-old female, a retransplanted kidney recipient from her daughter in 2012 on triple immunosuppressants with chronic kidney disease Stage IIIb, presented with fever, loss of appetite, right iliac fossa pain, and tiredness for 2 weeks. Her first kidney transplant was done in 1998 with external iliac vessels being used for the anastomosis. She is a diabetic, hypertensive, hypothyroid, and post-COVID status who had previously recurrent urinary tract infections since 2022. She was found to have a right iliac fossa mass at the site of the first kidney transplant, which was tender. Imaging including ultrasound and positron emission tomography/computed tomography showed a metabolically active right iliac fossa mass infiltrating the anterior abdominal wall. Surgery revealed a mass and on histopathology revealed a renal abscess which grew Candida ciferrii and tissue culture grew Enterobacter cloacae. She was treated with injection levofloxacin and tablet posaconazole and she recovered. This patient was presented for the interesting finding of coinfection in the late posttransplant period.

Incidence and Outcomes of BK Virus Nephropathy in Kidney Transplant Recipients With Steroid-Free Maintenance Immunosuppression

BackgroundBK virus nephropathy (BKVN) is a significant complication in kidney transplant recipients, resulting in graft dysfunction and potentially leading to graft loss. This study aims to investigate the incidence and outcomes of BKVN in kidney transplant recipients receiving steroid-free maintenance immunosuppression in a Latin -American cohort. MethodsCase series study of BKVN among kidney transplant recipients who underwent transplantation between 2008 and 2023. The primary outcome was graft loss caused by BKVN, excluding death with function. Secondary outcomes included graft function and acute rejection episodes. The statistical analysis involved descriptive statistics and the Kaplan-Meier (K-M) method to plot the overall probabilities of not initiating dialysis. ResultsDuring the 15-year period, 2236 kidney transplants were performed, BKVN was histologically diagnosed in 38 kidney recipients and 33 cases were analyzed. Median age was 50 years and men were 48.5% of patients. A total of 45.4% of BKVN occurred within the first 12 months of transplant. The incidence of BKVN was 1.6% but it varied by era. The rate of graft loss was 75.7% (25 cases). The K-M graft survival probability at 6 months and 12 months after diagnosis of BKVN was 38.3% (95% CI 24.7–59.4) and 22.3% (95% CI 11.7–42.8), respectively. ConclusionBKVN affected 1.6% of transplant recipients and it was associated with high-rate of graft loss. We observed that significant graft disfunction at the time of diagnosis resulted in worse outcomes with a reduced probability of graft survival.

Outcomes of Deceased Donor Kidney Recipients From the Same Donor Based on Donor-Recipient Sex Discordance.

Outcomes of deceased donor kidney transplant (DDKT) recipients from the same donor with donor-recipient sex discordance have been studied with inconsistent results. Adult DDKT where both kidneys from the same donor occurred at our center in two different recipients of different sexes were included. Outcomes were analyzed separately for male and female donors, based on the concordance or discordance between donor-recipient sex: Male-male (M-m) versus Male to female (M-f) or vice versa, F-f versus F-m. Acute rejection (AR) and uncensored graft failure were primary outcomes of interest. The univariate and multivariate risks for AR and graft failure were conducted using the Cox proportional hazards model and log-rank tests. A total of 130 donors, 84 male and 46 female fulfilled our selection criteria and were transplanted in 260 recipients. With respect to the concordant groups (M-m or F-f), sex discordance was not significantly associated with the risk of rejection in multivariate analysis (M-f vs. M-m HR 1.15 [0.53-2.53, P=0.72]; F-m vs. F-f HR 1.77 [0.71-4.39, P=0.23]). Sex discordance was also not significantly associated with graft failure in multivariate analysis. Interestingly, risk factors for AR differed among male donors and female donors. The higher calculated panel reactive antibodies (cPRA) and nonwhite recipients were at increased risk for AR in F-m, but not in M-f. Donor-recipient sex discordance was not significantly associated with AR or graft failure. Risk factors for AR may differ across male and female donors.

Evolving trends in immunosuppression use and cytomegalovirus infection risk over the past decade in kidney transplantation.

The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years. This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses. Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years. Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection. Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV. A more individualized immunosuppression regimen based on infection risk merits consideration.

Recent Insights in Noninvasive Diagnostic for the Assessment of Kidney and Cardiovascular Outcome in Kidney Transplant Recipients.

Kidney transplantation improves quality of life and prolongs survival of patients with end-stage kidney disease. However, kidney transplant recipients present a higher risk for cardiovascular events compared to the general population. Risk assessment for graft failure as well as cardiovascular events is still based on invasive procedures. Biomarkers in blood and urine, but also new diagnostic approaches like genetic or molecular testing, can be useful tools to monitor graft function and to identify patients of high cardiovascular risk. Many biomarkers have been introduced, whereas most of these biomarkers have not been implemented in clinical routine. Here, we discuss recent developments in biomarkers and diagnostic models in kidney transplant recipients. Because many factors impact graft function and cardiovascular risk, it is most likely that no biomarker will meet the highest demands and standards. We advocate to shift focus to the identification of patients benefitting from molecular and genetic testing as well as from analysis of more specific biomarkers instead of finding one biomarker fitting to all patients.

Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older.

Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60-69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45-54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. The median patient follow-up time was 9.3 y (interquartile range, 5.3-13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60-69 y and 45-54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60-69 y and 45-54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging.

Frailty and post-transplant adverse outcomes among kidney transplant recipients A systematic review and meta-analysis.

Frailty is a good predictor of adverse outcomes among older patients, especially those who have undergone surgery. The prevalence of frailty among kidney transplant candidates is higher than the general population. This study aimed to explore the predictive value of frailty on post-transplant adverse outcomes among kidney recipients. A systematic review was performed for relevant studies until May 20, 2022, using four databases (Embase, Medline, Cochrane, and PsycINFO) for prospective design studies (PROSPERP: CRD42022331022). Random-effect meta-analysis modeling was undertaken in RevMan 5.3 to estimate the predictive value of frailty on adverse outcomes after kidney transplant. This systematic review included 14 studies, eight of which were suitable for meta-analysis. Frailty increased the risk of mortality (pooled hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.48-2.64), surgical complications (risk ratio [RR] 2.14, 95% CI 1.01-4.54), death-censored graft failure (DCGF) (pooled HR 3.31, 95% CI 1.27-8.62), length of stay (LOS) (pooled RR 1.59, 95% CI 1.05-2.39), length of stay ≥2 weeks (pooled odds ratio [OR] 1.72, 95% CI 1.26-2.35), and other common adverse outcomes among kidney transplant recipients. Frailty is associated with adverse outcomes after kidney transplant. This systematic review suggests the importance of assessing frailty among kidney transplant candidates prior to transplantation. Further research focusing on pre-transplant assessment combined with frailty is warranted to improve kidney transplant management.

Pig organs in humans: a forum on xenotransplantation

ABSTRACT What if one of your organs, say, the kidney, the heart or the liver, deteriorates completely, and you are not lucky enough to have a human organ for transplantation? Do you want to receive an organ from a pig? That is not a joke, but a subject some physicians and researchers are working on—a field of research known as ‘xenotransplantation’.In 2022, David Bennett, a 57-year-old patient with terminal heart disease, received a pig heart and survived for 2 months after the surgery. Another recipient, Lawrence Faucette, survived for 40 days after similar surgery in 2023. Then, in 2024, Rick Slayman, the world's first recipient of a pig kidney, passed away 2 months after the surgery. Rick was able to get out of the hospital during these 2 months and the transplant team said there is no indication that his sudden passing was the result of failure of the pig kidney graft. Rather, it was related to his heart disease. In China, a liver xenotransplantation from pig to a brain-dead patient was reported in 2024 and the transplanted liver survived in the human body for as long as 10 days.On April 2024, National Science Review organized a panel discussion on xenotransplantation, which was chaired by Prof. Liangxue Lai and involved six other experts in the field. The panelists had in-depth discussions on xenotransplantation, covering its history and the (i) gene editing of the donor pigs, (ii) immunosuppressive regimens required by the recipients, (iii) challenges in preclinical and clinical research, (iv) relevant ethical issues and (v) prospects for the future of xenotransplantation. Gang Chen Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China David K.C. Cooper Massachusetts General Hospital, Harvard Medical School, Boston, USA Yifan Dai School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China Dengke Pan ClonOrgan Biotechnology Company, Neijiang, China Lin Wang Xijing Hospital, Air Force Medical University, Xi'an, China Xuan Zhang Xijing Hospital, Air Force Medical University, Xi'an, China Liangxue Lai (Chair) Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

Hypothermia for expanded criteria organ donors in kidney transplantation in France (HYPOREME): a multicentre, randomised controlled trial

Expanded criteria donors help to increase graft availability, but provide organs with an increased risk of delayed graft function. We aimed to investigate whether donor hypothermia decreases the risk of delayed graft function compared with normothermia. We did this multicentre, randomised, controlled, parallel-arm trial at 53 intensive care units and transplant centres in France. We included expanded criteria donors in whom death was diagnosed based on neurological criteria, in compliance with French law, and the recipients of their kidney grafts. Eligible expanded criteria donors were older than 60 years or were aged 50-59 years and had at least two other risk factors (history of hypertension, creatinine >132 μmol/L, or cerebrovascular cause of death). Donors were randomly assigned to hypothermia (34-35°C) or normothermia (36·5-37·5°C). Machine perfusion was used routinely. Randomisation was done using a computer-generated, interactive, web-response system, in permuted blocks (block size six), stratified by centre. Outcome assessors were masked; investigator masking was not feasible. The primary outcome was the proportion of kidney recipients with delayed graft function, defined as renal replacement therapy within 7 days after transplantation, assessed in the modified intention-to-treat (mITT) population, which included all recipients who received at least one kidney from an expanded criteria donor, with the exception of those under guardianship. Secondary outcomes in expanded criteria donors were the number of organs recovered and transplanted, kidney function, body temperature, total volume of fluids administered, blood pressure and need for vasopressors and inotropes, and adverse events (cardiovascular events, metabolic disturbances, and coagulation disorders). Secondary outcomes in kidney recipients were duration of hospital stay, kidney graft function and vital status at day 7, day 28, 3 months, and 1 year after transplantation, and adverse events (infections, cardiovascular events, and surgical complications). Secondary outcomes were assessed in the mITT population. The trial was registered at ClinicalTrials.gov, NCT03098706. Between Nov 9, 2017, and March 3, 2021, 365 donors were randomly assigned, of whom 298 (151 [51%] male, 147 [49%] female) provided kidneys to 526 recipients (323 [61%] male, 203 [39%] female). 251 recipients in the hypothermia group and 275 recipients in the normothermia group were included in the analysis. Graft function was delayed in 40 (16%) of 251 recipients in the hypothermia group and 58 (21%) of 275 recipients in the normothermia group (odds ratio 0·71 [95% CI 0·44-1·13]; p=0·14; absolute difference -5·2% [95% CI 11·8-1·5]). Compared with donors in the normothermia group, donors in the hypothermia group had higher highest mean arterial pressure (115 mm Hg [SD 22] vs 108 mm Hg [20]; p=0·001). 1 year after transplantation, recipients in the hypothermia group had a lower mean creatinine concentration (152·4 μmol/L [SD 59·1] vs 169·7 μmol/L [51·4]; p=0·0351) and a higher mean creatinine clearance (42·3 mL/min/1·73 m2 [15·8] vs 40·5 mL/min/1·73 m2 [17·9]; p=0·0414) than those in the normothermia group. No significant differences between groups were identified for any other secondary outcomes. Hypothermia in expanded criteria donors whose organs were routinely stored using machine perfusion did not decrease the frequency of delayed kidney graft function. However, hypothermia was associated with a lower serum creatinine concentration and a higher creatinine clearance 1 year after transplantation. French Ministry of Health and French Intensive Care Society.

T cell-mediated rejection and cancer risk in 579,905 organ transplant recipients.

10552 Background: Prolonged immunosuppression following organ transplant raises post-transplant malignancy (PTM) risk without affecting chronic rejection graft failure (CRGF) rates. Our study investigated if T cell responses during rejection could protect against cancer, whereas T cell suppression in PTM might prevent rejection. Methods: Data from 1987 to 2023 on adult first-time single-organ transplant recipients were collected from the UNOS-OPTN database, excluding those with a history of malignancy. Time-dependent Cox regression and landmark analyses (at 1, 2, 3, 5, 10, 15, and 20 years) were used to explore the link between rejection-induced graft failure (RGF) and PTM. Results: The study included 579,905 recipients (kidney 386,878, liver 108,390, heart 45,046, lung 37,643, pancreas 1,948), with a mean follow-up of 7.3 years. RGF occurred in 9.5% of recipients (kidney 12.1%, liver 1.8%, heart 3.9%, lung 12.0%, pancreas 10.2%; p&lt;0.001), with 2.1% experiencing acute rejection graft failure (ARGF) and 7.4%, CRGF. PTM occurred in 12.0% of recipients (kidney 9.9%, liver 12.4%. heart 20.9%, lung 22.6%, pancreas 11.3%; p&lt;0.001), including breast (0.5%), digestive (1.2%), genitourinary (1.7%), gynecologic (0.1%), head and neck (0.3%), hematologic (1.4%), musculoskeletal (0.1%), neurologic (0.0%), respiratory (1.1%), and skin/Kaposi sarcoma (6.4%). In recipients with RGF, PTM risk significantly decreased (HR 0.21 [0.19-0.24]; p&lt;0.001), with consistent trends observed across seven time landmarks (HR 0.20-0.07; p&lt;0.001). Both ARGF and CRGF were associated with lower PTM risk (HR 0.23 [0.18-0.29], 0.21 [0.19-0.24]; p&lt;0.001). In organ-specific analyses, kidney transplants showed similar outcomes for RGF, ARGF, and CRGF (HR 0.21-0.22; p&lt;0.001). Lung transplants exhibited significant risk reductions with RGF (HR 0.44 [0.22-0.89]; p=0.02) and CRGF (HR 0.47 [0.24-0.94]; p=0.03), with no significant results in other organs. All findings remained consistent even after excluding re-transplantations and deaths due to rejection. Excluding PTM-related deaths from PTM cases significantly lowered RGF risk (HR 0.69 [0.65-0.73]; p&lt;0.001), a trend that was consistent across all time landmarks (HR 0.51-0.80; p&lt;0.001). This inverse pattern was seen in kidney, liver, heart, and lung transplants (HR 0.90 [0.84-0.95], 0.21 [0.11-0.38], 0.21 [0.14-0.31], 0.18 [0.14-0.23]; p&lt;0.001) but not in pancreas transplants (HR 1.62 [0.69-3.77]; p=0.27). Conclusions: This study shows that rejection lowers cancer risk in kidney and lung transplants and that PTM reduces rejection risk in kidney, liver, heart, and lung transplants. Implementing enhanced cancer screening for those who have not experienced rejection may be considered. Further research is needed to elucidate the underlying T cell biology specific to each type of transplant.

Clinical characteristics of renal cell carcinoma in the transplanted kidney in renal transplant recipients: A systematic scoping review.

Clinical characteristics of renal cell carcinoma in the transplanted kidney in renal transplant recipients: A systematic scoping review.

Myosteatosis and not low muscle mass is associated with lower survival in kidney transplant recipients

AbstractBackgroundMyosteatosis, that is muscle fat infiltration, is an important marker of muscle quality, affecting quality of life and survival in patients with chronic kidney disease (CKD). However, the connection between myosteatosis, skeletal muscle index (SMI) and survival in kidney transplant (KTx) recipients remains unclear.MethodsThis retrospective observational study included a cohort of consecutive adult kidney recipients transplanted between 2010 and 2017 in Stockholm. Preoperative abdominal computed tomography (CT) images obtained after diagnosis of CKD 5 and within 36 months of transplantation were collected. Using established criteria, we measured muscle area at the third lumbar vertebra (L3 level) and identified low attenuation muscle, indicating myosteatosis. Each area was divided by height squared providing the SMI, and fatty muscle index (FMI). Given that there is no commonly accepted definition of sarcopenia, two cut‐offs for SMI were used to define low muscle mass, Cut‐off 1 (≤32.8 for women and ≤44.7 for men) and Cut‐off 2 (≤38.5 for women and ≤52.4 for men). Average radiodensity of skeletal muscle and Charlson comorbidity index were calculated for each patient. The influence on survival from SMI, FMI, SMI/FMI ratio, and radiodensity was analysed.ResultsOut of 582 KTx recipients, 266 (46%) had a pre‐transplant abdominal CT available. Applying SMI Cut‐off 1, 30 recipients (11%) had sarcopenia compared with 106 (40%) with Cut‐off 2. Neither SMI nor FMI was associated with survival. Yet there was an association between SMI/FMI ratio and survival, patients with the lowest quintile SMI/FMI ratio having a significantly lower survival when compared with the highest quintile, both in the crude model and when adjusted for age, gender, and comorbidity. Additionally, FMI, radiodensity, and SMI/FMI, but not SMI, were significantly associated with Charlson comorbidity index (P &lt; 0.01).ConclusionsThe SMI/FMI ratio may be associated with both pre‐transplant comorbidity and post‐transplant survival even though the significance of SMI is unclear. This suggests that SMI/FMI ratio is a better indicator of muscular impairment than skeletal muscle quantity alone. The finding may reflect the complex interplay between muscle mass, muscular fat infiltration and metabolic health, all important determinants of wellness and longevity. In summary, our study underscores the potential of the SMI/FMI ratio as a predictor of outcome after KTx, a finding possibly transferable to other patient populations.