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Background The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Methods In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, −0.1; 95% confidence interval [CI], −13.0% to 12.7%; P =.064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P <.001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. Clinical Trials Registration NCT02538172. [ABSTRACT FROM AUTHOR]

Summary: Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60–70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow‐up was 4.7 years. Failure‐free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure‐free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5‐year failure‐free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post‐transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure‐free outcome, with sustained quality of life. [ABSTRACT FROM AUTHOR]

Background Patients returning to dialysis after graft loss have high early morbidity and mortality. Methods We used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded. Results Seventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft. Conclusion In summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation. [ABSTRACT FROM AUTHOR]

In Switzerland, organ procurement is well organized at the national-level but transplant outcomes have not been systematically monitored so far. Therefore, a novel project, the Swiss Transplant Cohort Study (STCS), was established. The STCS is a prospective multicentre study, designed as a dynamic cohort, which enrolls all solid organ recipients at the national level. The features of the STCS are a flexible patient-case system that allows capturing all transplant scenarios and collection of patient-specific and allograft-specific data. Beyond comprehensive clinical data, specific focus is directed at psychosocial and behavioral factors, infectious disease development, and bio-banking. Between May 2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients involving 1,721 transplantations, and a total of 1,800 organs implanted in 15 different transplantation scenarios. 10 % of all patients underwent re-transplantation and 3% had a second transplantation, either in the past or during follow-up. 34% of all kidney allografts originated from living donation. Until the end of 2011 we observed 4,385 infection episodes in our patient population. The STCS showed operative capabilities to collect high-quality data and to adequately reflect the complexity of the post-transplantation process. The STCS represents a promising novel project for comparative effectiveness research in transplantation medicine. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors. Methods: We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry. Results: Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041). Conclusion: The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks. [ABSTRACT FROM AUTHOR]

Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants., Methods: We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants., Results: We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss., Conclusion: The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Deng, Frischnknecht, Wehmeier, de Rougemont, Villard, Ferrari-Lacraz, Golshayan, Gannagé, Binet, Wirthmueller, Sidler, Schachtner, Schaub and Nilsson.)

Background: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population., Methods: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity., Results: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild., Conclusions: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate., Clinical Trials Registration: Clinicaltrials.gov NCT03699839., Competing Interests: Potential conflicts of interest. O. M. reports receiving grants from Lophius Bioscience and participated in advisory boards of Takeda and MSD. N. J. M. reports receiving grants from the Swiss Transplant Cohort Study, receiving support for attending a meeting by Biotest, and participating in the board of the Swiss Society for Infectious Diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome., Methods: We investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants., Results: There was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (<6.5k), graft survival was not significantly different., Discussion: Our results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation., 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 de Rougemont, Deng, Frischknecht, Wehmeier, Villard, Ferrari-Lacraz, Golshayan, Gannagé, Binet, Wirthmueller, Sidler, Schachtner, Schaub, Nilsson and the Swiss Transplant Cohort Study.)

Background: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM)., Methods: We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls., Results: Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR., Conclusion: Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA., 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 © 2022 Frischknecht, Deng, Wehmeier, de Rougemont, Villard, Ferrari-Lacraz, Golshayan, Gannagé, Binet, Wirthmueller, Sidler, Schachtner, Schaub, Nilsson and the Swiss Transplant Cohort Study.)

We aimed to identify, assess, compare and map research priorities of patients and professionals in the Swiss Transplant Cohort Study. The project followed 3 steps. 1) Focus group interviews identified patients' ( n = 22) research priorities. 2) A nationwide survey assessed and compared the priorities in 292 patients and 175 professionals. 3) Priorities were mapped to the 4 levels of Bronfenbrenner's ecological framework. The 13 research priorities (financial pressure, medication taking, continuity of care, emotional well-being, return to work, trustful relationships, person-centredness, organization of care, exercise and physical fitness, graft functioning, pregnancy, peer contact and public knowledge of transplantation), addressed all framework levels: patient ( n = 7), micro ( n = 3), meso ( n = 2), and macro ( n = 1). Comparing each group's top 10 priorities revealed that continuity of care received highest importance rating from both (92.2% patients, 92.5% professionals), with 3 more agreements between the groups. Otherwise, perspectives were more diverse than congruent: Patients emphasized patient level priorities (emotional well-being, graft functioning, return to work), professionals those on the meso level (continuity of care, organization of care). Patients' research priorities highlighted a need to expand research to the micro, meso and macro level. Discrepancies should be recognized to avoid understudying topics that are more important to professionals than to patients., 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 © 2022 Beckmann, Mauthner, Schick, Rochat, Lovis, Boehler, Binet, Huynh-Do, De Geest, the Psychosocial Interest Group, and the Swiss Transplant Cohort Study.)

Introduction: The effect of age on health outcomes in kidney transplantation remains inconclusive. This study aimed to analyze the relationship between age at time of kidney transplantation with mortality, graft loss and self-rated health status in adult kidney transplant recipients. Methods: This study used data from the Swiss Transplant Cohort Study and included prospective data of kidney transplant recipients between 2008 and 2017. Time-to-event analysis was performed using Cox' regression analysis, and -in the case of graft loss- competing risk analysis. A random-intercept regression model was applied to analyse self-rated health status. Results: We included 2,366 kidney transplant recipients. Age at transplantation linearly predicted mortality. It was also predictive for graft loss, though nonlinearly, showing that recipients aged between 35 and 55 years presented with the lowest risk of experiencing graft loss. No relationship of age with self-rated health status was detected. Conclusion: Higher mortality in older recipients complies with data from the general population. The non-linear relationship between age and graft loss and the higher scored self-rated health status at all follow-up time-points compared to the pre-transplant status -regardless of age- highlight that age alone might not be an accurate measure for risk prediction and clinical decision making in kidney transplantation., 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 © 2022 Beerli, Denhaerynck, Binet, Dahdal, Dickenmann, Golshayan, Hadaya, Huynh-Do, Schnyder, De Geest and Mauthner.)

Purpose: The Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine., Participants: Over 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients., Findings to Date: Detailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the last decade. Interdisciplinary contributions in diverse fields of transplantation medicine such as infectious diseases, genomics, oncology, immunology and psychosocial science have resulted in approximately 70 scientific papers getting published in peer-review journals so far., Future Plans: The STCS will deepen its efforts in personalised medicine and digital epidemiology, and will also focus on allocation research and the use of causal inference methods to make complex matters in transplant medicine more understandable and transparent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Living donor renal transplantation is widely performed in Switzerland with a superior long-term outcome and lower waiting time compared with deceased renal transplantation. However the chances of receiving a living donor kidney transplant are not the same for all transplant candidates. The current study aimed to identify psychosocial and demographic characteristics that predict lower access to living kidney donation in Switzerland., Methods: The study was a nationwide multicentre study nested within the Swiss Transplant Cohort Study. Pre-transplant demographic, psychosocial and health characteristics of 1126 deceased and 859 living renal transplant recipients were compared using logistic regression analysis., Results: Transplant candidates with higher age (odds ratio [OR] per 10 years 0.67, 95% confidence interval [CI] 0.60&ndash;0.74), lower education (OR 0.46, 95% CI 0.36&ndash;0.59), a work capacity of less than 50% (OR 0.48, 95% CI 0.35&ndash;0.66), single or formerly married (OR 0.38, 95% CI 0.26&ndash;0.53 / OR 0.37, 95% CI 0.26&ndash;0.53) or with a higher hospital depression score (OR per 5 points 0.61, 95% CI 0.50&ndash;0.74) were less likely to receive an allograft from a living donor. In some regions of Switzerland candidates were more likely to undergo living transplantation than in other regions. No association was found with gender or income., Conclusions: Interventions to increase access to kidney transplantation from living donors should target transplant candidates of older age, lower education, lower working capacity and not living in a committed relationship. The observed regional differences suggest that additional determinants of living donation may play a role such as population and health professional attitudes toward living donation.

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis., Competing Interests: The authors have declared that no competing interests exist.

Background: The impact of pre-transplant social determinants of health on post-transplant outcomes remains understudied. In the United States, poor clinical outcomes are associated with underprivileged status, as assessed by the Social Adaptability Index (SAI), a composite score of education, employment status, marital status, household income, and substance abuse. Using data from the Swiss Transplant Cohort Study (STCS), we determined the SAI's predictive value regarding two post-transplant outcomes: all-cause mortality and return to dialysis., Methods: Between 2012 and 2018, we included adult renal transplant patients (aged ≥ 18 years) with pre-transplant assessment SAI scores, calculated from a STCS Psychosocial Questionnaire. Time to all-cause mortality and return to dialysis were predicted using Cox regression., Results: Of 1238 included patients (mean age: 53.8 ± 13.2 years; 37.9% female; median follow-up time: 4.4 years [IQR: 2.7]), 93 (7.5%) died and 57 (4.6%) returned to dialysis. The SAI's hazard ratio was 0.94 (95%CI: 0.88-1.01; p = .09) for mortality and 0.93 (95%CI: 0.85-1.02; p = .15) for return to dialysis., Conclusions: In contrast to most published studies on social deprivation, analysis of this Swiss sample detected no significant association between SAI score and mortality or return to dialysis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims of the Study: The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation., Methods: Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs)., Results: A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3&ndash;65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged &gt;65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7&ndash;6.0)., Conclusion: The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.

Aims of the Study: Primary maintenance immunosuppressive therapies for renal transplant recipients underwent significant changes in recent years. We aimed to assess time trends and the impact of immunosuppressive regimens in first renal transplant recipients without immunological risk (blood group incompatibility, pre-existing donor-specific antibodies, positive B/T cell cross-match) in a prospective national multicentre cohort., Methods: The Swiss Transplant Cohort Study (STCS) prospectively enrols all patients receiving solid organ transplants in Switzerland since 2008 and systematically collects high quality clinical and laboratory data using standardised definitions. The current STCS nested study enrolled all adult transplant-na&iuml;ve normal-immunological risk renal transplant recipients up to the end of 2017 and investigated different immunosuppressive strategies across a variety of transplantation relevant outcomes., Results: Of 1191 recipients enrolled at six transplant centres, 115 (10%) died with a functioning allograft and 92 (8%) lost their allograft during a median follow-up time of 5.8 years. The predominant immunosuppressive therapy comprised tacrolimus, mycophenolate mofetil and prednisone (73.7%), whereas 24.3% were treated with ciclosporin instead of tacrolimus. Primary immunosuppression with an mTOR inhibitor (1.1%) or other immunosuppressive combinations (0.8%) was rare. In the years following 2011, ciclosporin-based immunosuppression decreased significantly. The incidence of graft loss was significantly higher in patients with ciclosporin-based than with tacrolimus-based immunosuppression (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.29&ndash;2.14; p &lt;0.01), but the occurrence of acute transplant rejections did not differ significantly (adjusted HR 1.48, 95% CI 0.82&ndash;2.65; p = 0.19). The longitudinal course of the renal allograft function was significantly better (p = 0.013) in recipients of tacrolimus-based immunosuppressive therapy. Graft failure-free survival was higher (HR 1.25, 95% CI 0.97&ndash; 1.6; p = 0.08) with tacrolimus-based than with ciclosporin-based immunosuppression. Cytomegalovirus infections occurred more frequently with ciclosporin-based immunosuppression (9.7% vs 6.4% after 1 year), whereas the incidence of BK virus infections was similar in both groups. The median time to prednisone discontinuation was 1.9 years and did not differ between the two groups. Eleven cases of post-transplantation lymphoproliferative disorder were observed during the follow-up period (1 with ciclosporin-based and 10 with tacrolimus-based immunosuppression)., Conclusions: The available data show that primary maintenance immunosuppression with tacrolimus has displaced ciclosporin-based therapies. The tacrolimus-based immunosuppression therapy showed consistently better results across almost all assessed clinically relevant outcomes. (ClinicalTrials.gov Number: NCT01204944).

Background: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method., Methods: Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results., Results: Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%)., Conclusions: Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.

New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n 1  = 696). Positive results were tested in a first STCS replication sample (n 2  = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n 3  = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Weight gain after liver transplantation (LTx) facilitates development of new-onset obesity; however, its risk factors and outcomes are poorly understood. We identified the impact of new-onset obesity on cardiovascular events (CVEs) and patient survival, and risk factors for new-onset obesity. Multiple Cox regression models examined risk factors for CVEs, patient survival, and new-onset obesity in 253 adults (mean age 52.2 ± 11.6 years, male gender 63.6%, mean follow up 5.7 ± 2.1 years). Cumulative incidence of post-LTx CVE was 28.1%; that of new-onset obesity was 21.3%. Regardless of CVE at LTx, post-LTx CVEs were predicted by new-onset obesity [Hazard Ratio (HR), 2.95; P = 0.002] and higher age at LTx (HR, 1.05; P < 0.001). In patients without known pre-LTx CVEs (n = 214), risk factors for post-LTx CVEs were new-onset obesity (HR, 2.59; P = 0.014) and higher age (HR, 1.04; P = 0.001). Survival was not associated with new-onset obesity (P = 0.696). Alcoholic liver disease predicted new-onset obesity (HR, 3.37; P = 0.025), female gender was protective (HR, 0.39; P = 0.034). In 114 patients with available genetic data, alcoholic liver disease (HR, 12.82; P = 0.014) and hepatocellular carcinoma (HR, 10.02; P = 0.048) predicted new-onset obesity, and genetics remained borderline significant (HR, 1.07; P = 0.071). Early introduction of post-LTx weight management programs may suggest a potential pathway to reduce CVE risk., (© 2018 Steunstichting ESOT.)

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland., Methods: This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD., Results: We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined., Conclusions: At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Background and Objectives: Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored., Design, Settings, Participants, & Measurements: Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study., Results: In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions., Conclusions: There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion., (Copyright © 2015 by the American Society of Nephrology.)