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Background: Patients with end-stage kidney disease often prefer home-based dialysis due to higher self-efficacy, which relates to improved medical treatment adherence. Kidney transplantation (KT) success depends on adhering to immunosuppressive medication post-transplant., Objectives: To investigate whether adherence post-kidney transplantation (KT) and patients' attitudes toward immunosuppression were influenced by their prior dialysis type modality. Additionally, the study examined if adherence and patient's attitudes towards immunosuppression are associated with kidney graft survival., Methods: This cross-sectional single-center study included 201 KT patients. Adherence was assessed using BAASIS and the coefficient of variation of calcineurin inhibitors (COV-CNI). Patient attitudes towards medication were evaluated using the Q-method. Pill burden, comorbidity score and HRQoL and medication complexity, were scored. Cox regression was applied to determine KT survival outcomes over a 14-year follow-up period (until Dec 2021)., Results: Prior dialysis modality was not associated with adherence to immunosuppression post-KT evaluated by BAASIS on average 4.7 years post-KT. Previous in-center hemodialysis patients had a higher CNI-COV (p = 0.011). The Q-sort analysis identified fully adherent patients linked to profile 1 (organized, resilient) whereas profile 2 patients were more careless. Patients linked to profile 3 (challenging, nervous) had higher education, a higher pill burden, and experienced more immunosuppression side effects. Death-censored graft loss increased by 7.6% with each additional pill, quadrupled if one dose of immunosuppression was missed, and increased by 2.9% for each point of COV-CNI rise., Conclusions: Adherence to immunosuppression post-KT using BAASIS was not associated with prior dialysis type, despite in-center hemodialysis patients showing the highest COV-CNI. Taking COV-CNI into account, managing missed doses of immunosuppressants, and exploring patient attitudes could potentially enhance adherence and consequently improve KT survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ortiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

HLA typing and matching have been crucial in kidney transplantation, but methods for assessing tissue histocompatibility have advanced significantly. While serological-level HLA typing remains common, it captures only a small fraction of true HLA variation, and molecular matching is already replacing traditional HLA matching. Recent studies have expanded our understanding of genetic tissue compatibility beyond HLA loci. Candidate gene analyses and genome-wide association studies (GWAS) have identified genetic factors linked to post-transplant complications, though replication of these findings is challenging. An alternative approach involves genome-wide matching of genes or genetic variations. This method has shown promise in hematopoietic stem cell and kidney transplantation. For instance, homozygous gene deletions in LIMS1 or complement factor H (CFH) genes have been associated with acute rejection risk. This may be due to alloimmune responses against proteins absent in the patient but present in the graft, or due to the missing protein's function. Genetic studies in clinical medicine face challenges due to the interplay of genetic and environmental factors, necessitating large datasets for meaningful associations. International collaboration and large consortia, like iGeneTRAin, are essential for validating findings and advancing the field. This review highlights recent advancements in immunogenetics and tissue histocompatibility, emphasizing future research directions., Competing Interests: SM, JP, and KH are employed by the Finnish Red Cross Blood Service. Outside the current work, IH holds research funds from Hansa Biopharma and MSD, and has ongoing consultancy agreements with AstraZeneca, Hansa Biopharma, MSD, and Takeda., (Copyright © 2024 Helanterä, Markkinen, Partanen and Hyvärinen.)

Background: Lysinuric protein intolerance (LPI) is a metabolic disorder that leads to dysfunctional intestinal absorption and kidney clearance of cationic amino acids. Chronic kidney disease develops in many LPI patients and leads to end-stage kidney disease in at least 10% of patients. Since data on kidney transplants in LPI patients are limited, we analysed the outcomes of LPI patients after transplantation in Finland., Methods: This retrospective cohort study includes all Finnish LPI patients who have received a kidney transplant. The data were collected from the Finnish Transplant Registry and electronic medical records from 2005 through May 2023 or patient death. The plasma amino acid profile was analysed before and after transplantation., Results: Eight LPI patients (75% female, mean age at transplant 41.9 years) received a kidney allograft and two of the patients received a second transplant. Nine transplants were from deceased donors and one was from a living donor. Acute rejection occurred after four transplantations (two T-cell mediated and two antibody mediated). One patient died 6 months after transplantation due to alveolar proteinosis. Apart from lower citrulline and higher lysine concentrations, plasma amino acid levels showed no changes after transplantation. The 1-, 5- and 10-year graft survivals were 80%, 68.6% and 51.4%, and patient survivals were 88%, 86% and 50%, respectively., Conclusions: Kidney transplantation is feasible in patients with LPI, although the acute rejection rate seems high and severe complications such as pulmonary alveolar proteinosis may occur. Transplantation led to changes in plasma citrulline and lysine concentrations., Competing Interests: I.H. has received research funding from Hansa Biopharma and MSD and has ongoing consultancy agreements with AstraZeneca, Hansa Biopharma, MSD and Sandoz. K.A. receives lecture fees from Hansa Biopharma and Astellas. F.O. has consultancy agreements with Vifor, Takeda, GSK, MSD and Stada and receives lecture fees from AstraZeneca and Astellas. M.L. receives lecture fees from Astellas and is a board member of Scandiatransplant. S.K. receives support for attending meetings and/or travel from Novo Nordisk, Amicus and Kyowa Kirin., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes., Methods: We included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance., Results: Among 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach., Conclusions: Competing and noncompeting risk models performed similarly in predicting long-term kidney graft failure., (Copyright © 2024 by the American Society of Nephrology.)

The optimal calcineurin inhibitor after liver transplantation (LT) for primary biliary cholangitis (PBC) remains debated. We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis from the Scientific Registry of Transplant Recipients. We included adults with PBC who underwent primary LT from 1995 to 2022. Patients with initial cyclosporine treatment were 1:3 matched with those with initial tacrolimus treatment, ensuring exact calendar-period match. Primary outcomes were patient and graft survival. After matching, 579 patients with PBC and initial cyclosporine and 1348 with tacrolimus were well balanced for baseline characteristics. During a median follow-up of 11.1 years, 1044 (54%) deaths and 124 (6%) re-LTs occurred. In the overall matched sample, no significant survival difference emerged between cyclosporine and tacrolimus. However, tacrolimus conferred a survival advantage in some secondary analysis, such as LT after year 2000 and women, and in a 6-month landmark analysis excluding early postoperative events and calcineurin inhibitor switches. Cyclosporine did not reduce graft loss from PBC recurrence or affect laboratory markers of recurrence. In conclusion, we found no benefit of starting immunosuppression with cyclosporine after LT for PBC., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/- abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another., Methods: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival., Results: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy., Conclusions: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Kidney living donation carries risks, yet standardized information provision regarding nephrectomy risks and psychological impacts for candidates remains lacking., Objective: This study assesses the benefit of interactive health technology in improving the informed consent process for kidney living donation., Methods: The Kidney Hub institutional open portal offers comprehensive information on kidney disease and donation. Individuals willing to start the kidney living donation process at Helsinki University Hospital (January 2019-January 2022) were invited to use the patient-tailored digital care path (Living Donor Digital Care Path) included in the Kidney Hub. This platform provides detailed donation process information and facilitates communication between health care professionals and patients. eHealth literacy was evaluated via the eHealth Literacy Scale (eHEALS), usability with the System Usability Scale (SUS), and system utility through Likert-scale surveys with scores of 1-5. Qualitative content analysis addressed an open-ended question., Results: The Kidney Hub portal received over 8000 monthly visits, including to its sections on donation benefits (n=1629 views) and impact on donors' lives (n=4850 views). Of 127 living kidney donation candidates, 7 did not use Living Donor Digital Care Path. Users' ages ranged from 20 to 79 years, and they exchanged over 3500 messages. A total of 74 living donor candidates participated in the survey. Female candidates more commonly searched the internet about kidney donation (n=79 female candidates vs n=48 male candidates; P=.04). The mean eHEALS score correlated with internet use for health decisions (r=0.45; P<.001) and its importance (r=0.40; P=.01). Participants found that the Living Donor Digital Care Path was technically satisfactory (mean SUS score 4.4, SD 0.54) and useful but not pivotal in donation decision-making. Concerns focused on postsurgery coping for donors and recipients., Conclusions: Telemedicine effectively educates living kidney donor candidates on the donation process. The Living Donor Digital Care Path serves as a valuable eHealth tool, aiding clinicians in standardizing steps toward informed consent., Trial Registration: ClinicalTrials.gov NCT04791670; https://clinicaltrials.gov/study/NCT04791670., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2021-051166., (©Fernanda Ortiz, Juulia Grasberger, Agneta Ekstrand, Ilkka Helanterä, Guido Giunti. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.07.2024.)

Background and Hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient., Methods: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes., Results: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year., Conclusions: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function., (© 2024. The Author(s).)

Background: A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation., Methods: This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor-recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model., Results: The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40-60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential., Conclusions: The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: The clinical significance of kidney transplant protocol biopsies has been debated. We studied the frequency of borderline changes and T cell-mediated rejection (TCMR) in 1-y protocol biopsies in standard risk kidney transplant recipients., Methods: Consecutive non-HLA-sensitized recipients of kidney transplants between 2006 and 2017, who underwent a protocol biopsy at 1 y in 2 national transplant centers were studied retrospectively (N = 1546). Donor-specific HLA antibodies (DSAs), graft function (plasma creatinine), and proteinuria were measured at the time of 1-y protocol biopsy. The occurrence of subclinical acute TCMR (i2t2v0 or higher) or borderline changes suspicious of TCMR (i1t1v0 or higher) in the protocol biopsy was studied, together with frequency of findings causing changes in the composite score iBox., Results: Subclinical acute TCMR was detected in 30 of 1546 (1.9%) of the protocol biopsies, and borderline or TCMR in 179 of 1546 (12%). Among patients with no history of acute rejection, and no proteinuria or DSA, TCMR was detected in only 1 of 974 (0.1%) and borderline or TCMR in only 48 of 974 (4.9%) patients at 1 y. In the absence of proteinuria (<30 mg/g, or equivalent as measured with a negative dipstick proteinuria) or DSA, or history of acute rejection, only 50 of 974 (5.1%) biopsies showed any lesions significant for the iBox score., Conclusions: The likelihood of pathological findings in 1-y protocol biopsies in non-HLA-sensitized patients without previous immunological events is low. Clinical usefulness of protocol biopsies seems limited in these patients., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients ( n  = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R- patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R- SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis ( P  = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21-41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis., Competing Interests: The following authors have received speaker's fees from Astellas Pharma (KA, IH, ML, FO), Sandoz (IH, ML), Novartis (ML), Hansa Biopharma (KA, IH), Takeda (IH). IH holds research grant from MSD and Hansa Biopharma, and has ongoing consultancy agreements with MSD, Novartis, Hansa Biopharma, and Takeda. FO received consultancy honoraria from GSK, Sandoz, and STADA. AE serves on the advisory board of Baxter, Sanofi-Genzyme, Astra-Zeneca, and Vifor Pharma. ML Serves on the advisory board of Sandoz. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ahopelto, Grasberger, Ortiz, Ekstrand, Nordin, Lempinen and Helanterä.)

Background: Kidney disease is common after liver transplantation (LT), but postoperative kidney failure is difficult to predict. Current guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with pre-LT estimated glomerular filtration rate (eGFR) below 30-40 mL/min, which might be too liberal. The aim of this study was to evaluate the risk of kidney failure after LT. We also assessed the predictive ability of pretransplantation eGFR using various equations., Methods: This single-center study included patients undergoing primary LT 2006-2020. Patients undergoing simultaneous liver-kidney transplantations or on dialysis before LT were analysed separately. We calculated 5 different eGFR equations measured just before LT and assessed their predictive ability using Kaplan-Meier cumulative incidence estimates., Results: Among 556 LT patients with a median follow-up of 5.0 years (IQR 2.0-8.5), 20 developed kidney failure during follow-up, 7 of them within 1-year post LT. Six of these 7 suffered from major perioperative complications. Depending on the eGFR equation used, the incidence of kidney failure within 1-year was 3.9-6.7% at pre-LT eGFR-values <30 mL/min, 1.2-3.1% at eGFR 30-60 mL/min, and 0.6-0.9% at eGFR >60 mL/min., Conclusions: Kidney failure within 1-year post-LT could not be reliably predicted by pre-LT eGFR. However, kidney failure was uncommon even in patients with severely reduced pre-LT glomerular filtration rate (eGFR <30 mL/min), and extremely rare in patients unaffected by major perioperative complications. Our data prompts further consideration regarding the guidelines for SLKT in patients with a reduced preoperative eGFR.

Background: Cardiovascular diseases are an important cause of mortality in patients who have undergone kidney transplantation, but the knowledge on trends of cardiovascular mortality and specific causes of cardiovascular death among these patients is scarce., Methods: Our aim was to compare the cardiovascular mortality rates after kidney transplantation in Finland between 1990-1999, 2000-2009, and 2010-2019 using data from the Finnish Registry for Kidney Diseases. We analyzed 1-year and long-term cardiovascular mortality rates as well as the specific causes of cardiovascular death and the trends in them., Results: In total, 4946 patients underwent first kidney transplantation in 1990-2019. During the follow-up time (median 8.3 years, interquartile range 4.0-14.5), there were 1392 deaths, of which 582 were cardiovascular deaths. In an unadjusted Cox regression model, the risk of long-term cardiovascular mortality was similar in the different periods. However, when adjusted for age, sex, duration of dialysis, and cause of kidney disease, the long-term cardiovascular mortality risk was significantly lower in 2000-2009 and 2010-2019 (hazard ratio 0.60 [95% confidence interval, 0.49 to 0.73] and hazard ratio 0.51 [95% confidence interval, 0.39 to 0.66], respectively) compared with 1990-1999. The results were similar regarding 1-year cardiovascular mortality. The distribution of different causes of cardiovascular death remained unchanged during the study period, with coronary artery disease accounting for 47% of deaths. During the first year after transplantation, pulmonary embolisms and arrhythmias were more common than in the long term., Conclusions: Cardiovascular disease remained the most common cause of death in kidney transplant recipients, but adjusted cardiovascular mortality risk has decreased significantly during the past three decades. Coronary artery disease was the most frequent cause of cardiovascular death, and the proportion of coronary artery disease-related cardiovascular deaths increased after the first year after transplantation., (Copyright © 2023 by the American Society of Nephrology.)

Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland ( n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry ( n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors., Competing Interests: IH holds research grants from Hansa Biopharma, and MSD and has received consultancy fees from AstraZeneca, Hansa Biopharma, Takeda, and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ahlmark, Sallinen, Eerola, Lempinen and Helanterä.)

The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups., Competing Interests: IH reports receiving consulting fees from Novartis, Hansa Biopharma, MSD, and Takeda, and research funding from MSD and Hansa Biopharma outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grasberger, Ortiz, Ekstrand, Sallinen, Ahopelto, Finne, Gissler, Lempinen and Helanterä.)

Background & Aims: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US., Methods: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates., Results: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant., Conclusions: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC., Impact and Implications: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019., Methods: This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program., Results: During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in ≥3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility.Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023., Conclusions: The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Despite advances in monitoring and treatment, cytomegalovirus (CMV) infections remain one of the most common complications after solid organ transplantation (SOT). CMV infection may fail to respond to standard first- and second-line antiviral therapies with or without the presence of antiviral resistance to these therapies. This failure to respond after 14 days of appropriate treatment is referred to as "resistant/refractory CMV." Limited data on refractory CMV without antiviral resistance are available. Reported rates of resistant CMV are up to 18% in SOT recipients treated for CMV. Therapeutic options for treating these infections are limited due to the toxicity of the agent used or transplant-related complications. This is often the challenge with conventional agents such as ganciclovir, foscarnet and cidofovir. Recent introduction of new CMV agents including maribavir and letermovir as well as the use of adoptive T cell therapy may improve the outcome of these difficult-to-treat infections in SOT recipients. In this expert review, we focus on new treatment options for resistant/refractory CMV infection and disease in SOT recipients, with an emphasis on maribavir, letermovir, and adoptive T cell therapy., Competing Interests: RA has received grant/research support from Aicuris, Astellas, Astra-Zeneca, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda. NK is member of advisory boards of MSD Merck Sharp & Dohme, Pfizer and Gilead Sciences and member of the data safety management boards of Pulmocide and Idorsia Pharmaceuticals Ltd. IH holds research grants for investigator-initiated studies from MSD and Hansa Biopharma, and has ongoing consultancy agreements with Hansa Biopharma, MSD, Novartis, and Takeda. IH is an associate editor of Transplant International. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Walti, Khanna, Avery and Helanterä.)

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Kidney transplantation is the preferred treatment for individuals with end-stage kidney disease. From a modeling perspective, our understanding of kidney function trajectories after transplantation remains limited. Current modeling of kidney function post-transplantation is focused on linear slopes or percent decline and often excludes the highly variable early timepoints post-transplantation, where kidney function recovers and then stabilizes. Using estimated glomerular filtration rate (eGFR), a well-known biomarker of kidney function, from an aggregated dataset of 4904 kidney transplant patients including both observational studies and clinical trials, we developed a longitudinal model of kidney function trajectories from time of transplant to 6 years post-transplant. Our model is a nonlinear, mixed-effects model built in NONMEM that captured both the recovery phase after kidney transplantation, where the graft recovers function, and the long-term phase of stabilization and slow decline. Model fit was assessed using diagnostic plots and individual fits. Model performance, assessed via visual predictive checks, suggests accurate model predictions of eGFR at the median and lower 95% quantiles of eGFR, ranges which are of critical clinical importance for assessing loss of kidney function. Various clinically relevant covariates were also explored and found to improve the model. For example, transplant recipients of deceased donors recover function more slowly after transplantation and calcineurin inhibitor use promotes faster long-term decay. Our work provides a generalizable, nonlinear model of kidney allograft function that will be useful for estimating eGFR up to 6 years post-transplant in various clinically relevant populations., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland., Methods: In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics., Results: A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB., Conclusions: The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB., Competing Interests: The other authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Introduction: Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program., Methods: This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records., Results: A total of 166 SPKs were performed (median 2 per year in the first 3 years, 17.5 per year for the following 4 years, and 23 per year for the past 3 years). Seven patients (4.1%) died with a functioning graft with a median 43 months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36 mmol/mol (SD 5.57) and creatinine was 107 μmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N = 28). No pancreas or kidney graft failure from thrombosis occurred., Conclusion: A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A brain-death-induced cytokine storm damages organs in an organ donor. However, a longer time period between declaration of brain death and organ procurement (procurement interval) is associated with improved outcomes in kidney, liver, heart, and lung transplantation. The aim of this study was to find the optimal procurement interval for pancreas transplantation. Association of procurement interval with pancreas graft outcomes was analyzed using multivariable models adjusted for variables possibly affecting procurement interval and outcomes. Altogether 10,119 pancreas transplantations were included from the Scientific Registry of Transplant Recipients. The median follow-up was 3.2 (IQR 1.01-6.50) years. During the first year, 832 (9.0%) grafts were lost, including 555 (6.0%) within the first 30 days. Longer procurement interval was associated with increased death-censored graft survival in a multivariable model (HR 0.944 95% CI 0.917-0.972, per 10-h increase, p < 0.001). A decreasing hazard of graft loss was observed also with 1-year, but not with 30-day graft survival. During 1-year follow-up, 953 (12.1%) patients had an acute rejection, and longer procurement interval was also associated with less acute rejections (OR 0.937 95% CI 0.900-0.976, per 10-h increase, p = 0.002) in the multivariable model. In conclusion, longer procurement interval is associated with improved long-term outcomes in pancreas transplantation., Competing Interests: IH reports receiving consulting fees from Novartis, Hansa Biopharma, and Takeda, and research funding from MSD and Hansa Biopharma outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eerola, Sallinen, Lempinen and Helanterä.)

In elective pancreatic surgery, somatostatin-analogues pasireotide and octreotide are variably used to reduce postoperative complications, but knowledge on their role in pancreas transplantation is limited. This study compared pasireotide and octreotide for their association with complications after simultaneous pancreas-kidney transplantation (SPK). This retrospective study included consecutive patients undergoing SPK's from July 2013 to July 2022. Between July 2013 and April 2020, octreotide was administered 0.1 mg s.c. once daily and between May 2020 and July 2022 pasireotide was administered 0.9 mg twice daily, both until third postoperative day. Complications within 90 days postoperatively were collected, and reoperation rate and Comprehensive Complication index (CCI) ≥ 33.7 (morbidity equal to one reoperation) were used as primary outcomes. Of the 213 patients undergoing SPK, 150 patients received octreotide and 63 pasireotide. Baseline characteristics were comparable. Reoperation rate was 25.3% ( n = 38) and 17.5% ( n = 11) ( p = 0.213) and rate of CCI ≥ 33.7 was 40.7% ( n = 61) and 30.2% ( n = 19) ( p = 0.148) in octreotide and pasireotide groups, respectively. When adjusted with donor BMI, pancreas donor risk index, and donor sex, receiving pasireotide translated into OR 0.49 (95% CI: 0.25-0.96 p = 0.037) for CCI ≥ 33.7. Pasireotide was independently associated with lower postoperative morbidity within 90 days of SPK compared to octreotide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahopelto, Bonsdorff, Grasberger, Lempinen, Nordin, Helanterä and Sallinen.)

Competing Interests: Unrelated to the current manuscript, I.H. holds research funds from MSD and Hansa Biopharma and is receiving consultancy honoraria from Novartis, Hansa Biopharma, and Takeda. The other authors declare no conflicts of interest.