Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

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.

Deceased donor kidney transplanted in childhood functioning well after 52 years.

BACKGROUND: Kidney transplantation in children in 1970 was considered by many to be unethical, as long-term survival was minimal. It was therefore risky at the time to offer transplantation to a child. CASE DIAGNOSIS/TREATMENT: A 6-year-old boy with kidney failure due to haemolytic uraemic syndrome received 4 months of intermittent peritoneal dialysis followed by 6 months of haemodialysis until at 6 years and 10 months, he underwent bilateral nephrectomy and received a kidney transplant from a deceased 18-year-old donor. Despite moderate long-term immunosuppression of prednisone (20 mg/48 h) and azathioprine (62.5 mg/day), at the last visit in September 2022, he was well, normotrophic, with a serum creatinine of 157 µmol/l (eGFR 41 ml/min/1.73 m2) and no haematuria, proteinuria or hypertension. Except for benign skin lesions due to azathioprine, and undergoing an aortic valve replacement and an aortic aneurysm repair in adulthood, the now 58-year-old man has had no major complications. CONCLUSIONS: We speculate that stable and unmodified immunosuppressive therapy, started before the era of calcineurin inhibitors, the lack of significant rejection episodes, the absence of donor-specific antibodies, and the young donor age have contributed to maintaining exceptional long-term kidney transplant survival. Luck, a robust health system and an adherent patient are also important. To the best of our knowledge, this is the longest functioning kidney transplant from a deceased donor performed in a child worldwide. Despite its risky nature at the time, this transplant paved the way for others.

Anonymity in Kidney Paired Donation: A Systematic Review of Reasons.

The objective of this study was to investigate reasons for or against anonymity that are pertinent to kidney paired donations (KPD). We conducted a systematic review of reasons using PubMed and Google Scholar until May 2022 and through snowballing. Inclusion criteria were publications that: 1) discussed organ donation anonymity; 2) was peer-reviewed; 3) presented at least one reason on anonymity. Exclusion criteria: 1) not published in a scientific journal; 2) grey literature and dissertations. Four researchers independently reviewed and selected papers based on the criteria, extracted text passages and coded them into narrow and broad reason types, selected reasons that were valid for kidney paired donations. 50 articles were included, 62 narrow reasons (n = 24 for; n = 38 against) and 13 broad reasons were coded. Broad reasons were: protection against harm, general benefits, gratitude, curiosity, unrealistic to implement, fundamental rights, respect people's wishes, professional neutrality, timing is important, information disclosure, altruism, reciprocity and donation pool. We did not find reasons that justify legal prohibition of donor-recipient interactions for KPD, if they consented to meet. Professional counselling, follow-up and careful evaluations to prevent potential harm.

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. METHODS: The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. FINDINGS: Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. INTERPRETATION: In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. FUNDING: Swiss National Science Foundation.

Recurrence of IgA nephropathy after kidney transplantation: experience from the Swiss transplant cohort study.

BACKGROUND: Recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in about 30% of patients. The relevance of recurrence for the long-term graft survival is expected to increase, since graft survival continues to improve. METHODS: In a nested study within the Swiss Transplant Cohort Study the incidence of IgAN recurrence, predictive factors, graft function and graft and patient survival were evaluated. Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex were measured using ELISA-based immunologic assays. RESULTS: Between May 2008 and December 2016, 28 women and 133 men received their kidney allograft for end-stage kidney disease due to IgAN in Switzerland. Over a median follow-up time of 7 years after transplantation, 43 out of 161 patients (26.7%) developed an IgAN recurrence, of which six (13.9%) had an allograft failure afterwards and further four patients (9.3%) died. During the same follow-up period, 6 out of 118 patients (5%) each experienced allograft failure or died without prior IgAN recurrence. After 11 years the risk for IgAN recurrence was 27.7% (95%-CI: 20.6-35.3%). Renal function was similar in patients with and without recurrence up to 7 years after transplantation, but worsened thereafter in patients with recurrence (eGFR median (interquartile range) at 8 years: 49 ml/min/1.73m2 (29-68) vs. 60 ml/min/1.73m2 (38-78)). Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex within the first year posttransplant showed no significant effect on the recurrence of IgAN. Younger recipients and women had a higher risk of recurrence, but the latter only in the short term. CONCLUSIONS: Our study showed a recurrence risk of 28% at 11 years after transplantation, which is consistent with previous literature. However, the predictive value of known biomarkers, such as serum Gd-IgA1 and IgA-IgG IC, for IgAN recurrence could not be confirmed.

Infection Risk in the First Year After ABO-incompatible Kidney Transplantation: A Nationwide Prospective Cohort Study.

BACKGROUND: ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised. METHODS: In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection. RESULTS: We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461). CONCLUSIONS: The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1-2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long-term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Sustained Trichodysplasia Spinulosa Polyomavirus Viremia Illustrating a Primary Disseminated Infection in a Kidney Transplant Recipient.

Novel human polyomaviruses (HPyV) have been recently identified in solid organ transplant recipients. Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus (TSPyV). We report here a case of primary and disseminated TSPyV infection after kidney transplantation with extensive skin lesions, sustained viremia, and high viral loads in urine specimens, anal, nasal and throat swabs, assessed via specific real-time PCR for TSPyV during a follow-up period of 32 months after transplantation. The detection of TSPyV with a high viral load in respiratory and anal swab samples is compatible with viral replication and thus may suggest potential respiratory and oro-fecal routes of transmission.

Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study.

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2 ) at one year. Two hundred and twenty-one (221/2215; 10%) transplants showed a poor first-year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First-year patient's death was rare (48/2215; 2%). There were no statistically significant differences between DSA-positive and DSA-negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA-positive transplants experienced more frequently rejection episodes, mainly antibody-mediated rejection (both P < 0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death-censored allograft survival (P < 0.0001). In conclusion, presence of pre-transplant DSA per se does not affect first year outcomes. However, DSA-positive transplants experiencing first year rejection are a high-risk population for poor allograft survival and may benefit from intense clinical surveillance.

Demographic, psychosocial and health disparities between living and deceased renal allograft recipients in Switzerland.

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] 0.60–0.74), lower education (OR 0.46, 95% CI 0.36–0.59), a work capacity of less than 50% (OR 0.48, 95% CI 0.35–0.66), single or formerly married (OR 0.38, 95% CI 0.26–0.53 / OR 0.37, 95% CI 0.26–0.53) or with a higher hospital depression score (OR per 5 points 0.61, 95% CI 0.50–0.74) 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.

Successful treatment of central nervous system lymphoproliferative disorder in a kidney-pancreas and stem cell transplanted patient using intrathecal rituximab.

Central nervous system lymphoproliferative disorder (CNS-PTLD) after organ transplant is a unique clinicopathological entity and is associated with poor survival rates. When the CNS is involved, intravenous rituximab might not be the treatment of choice, due to its poor CNS penetration. However, intrathecal (IT) administration of rituximab has shown to be safe and efficient in small studies and in case series. We report here the case of a patient with late development of CNS-PTLD after kidney-pancreas transplantation who achieved complete remission after surgical resection and four cycles of IT rituximab and we provide a review of the literature for this treatment option.

Infectious complications and graft outcome following treatment of acute antibody-mediated rejection after kidney transplantation: A nationwide cohort study.

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.

Data and optimisation requirements for Kidney Exchange Programs.

Kidney Exchange Programs (KEP) are valuable tools to increase the options of living donor kidney transplantation for patients with end-stage kidney disease with an immunologically incompatible live donor. Maximising the benefits of a KEP requires an information system to manage data and to optimise transplants. The data input specifications of the systems that relate to key information on blood group and Human Leukocyte Antigen (HLA) types and HLA antibodies are crucial in order to maximise the number of identified matched pairs while minimising the risk of match failures due to unanticipated positive crossmatches. Based on a survey of eight national and one transnational kidney exchange program, we discuss data requirements for running a KEP. We note large variations in the data recorded by different KEPs, reflecting varying medical practices. Furthermore, we describe how the information system supports decision making throughout these kidney exchange programs.

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

Outcome of kidney transplantation from very senior donors in Switzerland - a national cohort study.

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.

Age at Time of Kidney Transplantation as a Predictor for Mortality, Graft Loss and Self-Rated Health Status: Results From 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.

SARS-CoV-2 / COVID-19 in patients on the Swiss national transplant waiting list.

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 45.3–65.8), 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 >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 2.7–6.0). 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.

Immunosuppression management in renal transplant recipients with normal-immunological risk: 10-year results from the Swiss Transplant Cohort Study.

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-naïve 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] 1.29–2.14; p <0.01), but the occurrence of acute transplant rejections did not differ significantly (adjusted HR 1.48, 95% CI 0.82–2.65; 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– 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).

Dialysis after graft loss: a Swiss experience.

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.

[Diabetes after kidney transplantation†: current knowledge]. / Diabète après transplantation rénale†: mise au point.

The onset of diabetes after kidney transplantation is a frequently encountered entity by both the nephrologist, the diabetologist and the primary care physician. This article discusses various aspects related to diabetes after kidney transplantation such as epidemiology, risk factors, pathogenesis, diagnosis, associated complications and therapeutic management.

La survenue d'un diabète après transplantation rénale est une entité fréquemment rencontrée tant par le néphrologue, le diabétologue que par le médecin de premier recours. Cet article fait le point sur différents aspects liés au diabète après transplantation rénale tels que l'épidémiologie, les facteurs de risque, la pathogenèse, le diagnostic, les complications associées et la prise en charge thérapeutique.