Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).

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.

Outcome of kidney transplantation from senior deceased donors: a single centre study.

BACKGROUND: Addressing the current demographic development, the efficacy and safety of kidney transplantations from very senior donors needs to be carefully evaluated. The aim of this study was to analyse patient and graft outcomes of kidney allograft recipients stratified by donor age. METHODS: We retrospectively investigated n = 491 patients from a prospective, observational renal transplant cohort. Patients with kidneys from very old donors (n = 75, aged >70 years), elderly donors (n = 158, between 60-70 years), and regular donors (n = 258, aged <60 years) were investigated. The primary outcome was death-censored graft survival within the predefined donor age groups. RESULTS: Overall, n = 57 death-censored graft losses occurred. Graft loss was proportionally highest in the very old donor group (n = 11/75), but this did not reach statistical significance when compared to the elderly (14/158) and regular donor groups (32/258); (p = 0.37). Kaplan-Meier analysis demonstrated that 3-year/5-year death-censored graft survival in the very old donor group was 96%/86% and did not differ from the other age groups (p = 0.44). Median estimated glomerular filtration rate (eGFR), calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (in ml/min/1.73 m2 of body surface) 12 months post-transplant did not differ between the elderly donor and very old donor groups (p = 0.53). However, patients who received regular donor kidneys had higher median eGFR compared to recipients in both the elderly and very old donor groups (p <0.0001). During follow-up, 31% of patients developed at least one acute rejection episode. Time-to-event analysis demonstrated no difference in occurrence of any acute rejection event across all three groups (p = 0.11). CONCLUSIONS: This study demonstrates that kidney transplantation from carefully selected very old donors seems a valid option with reasonable short- and mid-term outcomes.

Urine CXCL10 to Assess BK Polyomavirus Replication After Kidney Transplantation.

BACKGROUND: Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication. METHODS: We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d. RESULTS: Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol. CONCLUSIONS: Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty.

Randomized Trial to Assess the Clinical Utility of Renal Allograft Monitoring by Urine CXCL10 Chemokine.

SIGNIFICANCE STATEMENT: This study is the first randomized controlled trial to investigate the clinical utility of a noninvasive monitoring biomarker in renal transplantation. Although urine CXCL10 monitoring could not demonstrate a beneficial effect on 1-year outcomes, the study is a rich source for future design of trials aiming to explore the clinical utility of noninvasive biomarkers. In addition, the study supports the use of urine CXCL10 to assess the inflammatory status of the renal allograft. BACKGROUND: Urine CXCL10 is a promising noninvasive biomarker for detection of renal allograft rejection. The aim of this study was to investigate the clinical utility of renal allograft monitoring by urine CXCL10 in a randomized trial. METHODS: We stratified 241 patients, 120 into an intervention and 121 into a control arm. In both arms, urine CXCL10 levels were monitored at three specific time points (1, 3, and 6 months post-transplant). In the intervention arm, elevated values triggered performance of an allograft biopsy with therapeutic adaptations according to the result. In the control arm, urine CXCL10 was measured, but the results concealed. The primary outcome was a combined end point at 1-year post-transplant (death-censored graft loss, clinical rejection between month 1 and 1-year, acute rejection in 1-year surveillance biopsy, chronic active T-cell-mediated rejection in 1-year surveillance biopsy, development of de novo donor-specific HLA antibodies, or eGFR <25 ml/min). RESULTS: The incidence of the primary outcome was not different between the intervention and the control arm (51% versus 49%; relative risk (RR), 1.04 [95% confidence interval, 0.81 to 1.34]; P = 0.80). When including 175 of 241 (73%) patients in a per-protocol analysis, the incidence of the primary outcome was also not different (55% versus 49%; RR, 1.11 [95% confidence interval, 0.84 to 1.47]; P = 0.54). The incidence of the individual end points was not different as well. CONCLUSIONS: This study could not demonstrate a beneficial effect of urine CXCL10 monitoring on 1-year outcomes (ClinicalTrials.gov_ NCT03140514 ).

Differences Between Centers in Psychosocial Evaluations for Living Kidney Donors Do Not Influence Outcome: Results From an Observational Multicenter Study.

Rather little is known about how psychosocial evaluations for living kidney donation (LKD) are performed. We aimed to explore whether Swiss transplant centers (STCs) vary regarding the rate of living kidney donors refused for psychosocial reasons, the psychosocial evaluation process, and the characteristics of the donors. Methods: We investigated 310 consecutive candidates for LKD in 4 of 6 existing STC during mandatory psychosocial evaluations. We registered (i) sociodemographic data, (ii) the type of the decision-making process regarding LKD (ie, snap decision, postponed, deliberate, other), (iii) the evaluator's perception of the donor's emotional bonding and his/her conflicts with the recipient, (iv) the donor's prognosis from a psychosocial perspective, (v) time taken for the psychosocial evaluation, and (vi) its result (eligible, eligible with additional requirements, not eligible). Results: Centers had comparable proportions of noneligible donors (2.9%-6.0%) but differed significantly in the percentage of donors accepted with additional requirements (3.4%-66%, P < 0.001). Significant differences emerged between centers regarding the time needed for evaluation (75-160 min [interquartile range (IQR) 75-180 min] per single exploration, P < 0.001), the perception of the donor's emotional bonding (visual analogue scale [VAS] 8-9 [IQR 6-10], P < 0.001), his/her conflicts with the recipient (VAS 1.5-2 [IQR 0-3], P = 0.006), the donor's psychosocial prognosis (VAS 8-9 [IQR 7-10], P < 0.001), and the type of decision concerning LKD (59%-82% with snap decision "yes," P = 0.008). However, despite differences in the psychosocial evaluation process, the rates of patients accepted for transplantation (eligible and eligible with additional requirements versus noneligible) were comparable across STC (P = 0.72). Conclusions: Our results emphasize that it is more important to establish clear guidelines to identify potential psychosocial risks than to stringently standardize the procedure for psychosocial evaluation of living kidney donors.

Cohort profile: The Swiss Transplant Cohort Study (STCS): A nationwide longitudinal cohort study of all solid organ recipients in Switzerland.

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.

Evolution of disability pension after renal transplantation: methods and results of a database linkage study of the Swiss Transplant Cohort Study and Swiss Disability Insurance.

AIMS: In Switzerland, certain patients with disabilities and reduced working ability are entitled to a disability pension granted by the Swiss Federal Social Insurance Office (FSIO). The aim was to assess the evolution of disability pension and work capacity after kidney transplantation and thereby pilot the procedures linking FSIO data with Swiss Transplant Cohort Study (STCS) data. METHODS: The current study pilot tested the record linkage of FSIO data with data from the STCS in a single-centre, observational setting. Patients were requested to consent to the use of their Swiss social security number (SSSN) for the purpose of record linkage. A privacy preserving trust centre approach was implemented with blinded statistical analysis. RESULTS: Between May 2008 and December 2015, 282 working-age renal transplant recipients of the University Hospital of Basel transplant centre were eligible for inclusion and 136 (48%, median age 48 years) consented to the use of their social security number and record linkage. The FSIO datasets of all patients were successfully retrieved and linked to STCS data in the trust centre and were numerically analysable. Yearly FSIO allowance data were available for the entire study duration. Fifty-five patients (40%) were registered as disability insurance recipients (DIR). In the entire population, the proportion of working patients slightly decreased from 76% to 72% between the pre-transplant and the post-transplant period. This was due to the lower proportion of patients working after transplantation in DIR compared with non-recipients (non-DIR) (DIR: 60% before vs 44% after; non-DIR: 83% before vs 88% after). In the DIR group, the proportion of patients not working increased from 36% to 49%, whereas in non-DIR the proportion changed only marginally (14% to 12%). The average disability insurance allowance was CHF 1172 per month. It changed from CHF 1135 before transplantation to CHF 1209 after transplantation (p = 0.59). CONCLUSIONS: In the Swiss healthcare and social insurance system, record linkage studies combining clinical datasets with data from FSIO are feasible but associated with great efforts and resource needs. The lack of changes in disability allowances after kidney transplantation should be further investigated in the nationwide setting.

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.

Outcome of Husband-to-Wife Kidney Transplantation With Mutual Children: Single Center Experience Using T Cell-Depleting Induction and Review of the Literature.

Few data on husband-to-wife transplantations with mutual children (H2W) exist in the current era. We investigated the outcome of H2W transplantations (n = 25) treated with T cell-depleting induction compared to women with prior pregnancies also receiving their first HLA-mismatched kidney transplant, but from a different donor source: (i) other living donor (n = 52) and (ii) deceased donor (n = 120). Seventy-four percent of the women had ≥2 pregnancies; median follow-up time was 5 years. Death-censored allograft survival was significantly lower in the H2W group compared to the other two groups (p = 0.03). Three of four graft losses in the H2W group were due to rejection. 5-year patient survival in the H2W group was high and similar compared to the other living donor group (100 vs. 98%; p = 0.28). The incidence of (sub)clinical antibody-mediated rejection was higher in the H2W group (36 vs. 20 vs. 18%) (p = 0.10). The frequency of infections was similar among the three groups. No immunological parameter was predictive for rejection or graft loss in H2W transplantations. In conclusion, H2W transplantation is a valuable option, but associated with a higher risk for allograft loss due to rejection despite T cell-depleting induction. Further research is required for better risk prediction on an individual patient level.

Temporal trends of COVID-19 related in-hospital mortality and demographics in Switzerland - a retrospective single centre cohort study.

AIMS: The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland. METHODS: In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients’ characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality. RESULTS: During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53–76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45–2.26; p <0.001), male sex (aOR 1.68, 95% CI 1.00–2.82; p = 0.048), immunocompromising condition (aOR 2.09, 95% CI 1.01–4.33; p = 0.048) and chronic kidney disease (aOR 2.25, 95% CI 1.35–3.76; p = 0.002). CONCLUSION: In our study in-hospital mortality was 9.5%, 10.2% and 5.4% in the first, second and third waves, respectively. Age, immunocompromising condition, male sex and chronic kidney disease were factors associated with in-hospital mortality. Importantly, patients without any comorbidity had a very low in-hospital mortality regardless of age.

Short- and long-term impact of neutropenia within the first year after kidney transplantation.

The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (<1.5-1.0*109 /l; n = 105), grade 3 (<1.0-0.5*109 /l; n = 65), and grade 4 (<0.5*109 /l; n = 55). Most neutropenia episodes were presumably drug-related (71%) and managed by reduction/discontinuation of potentially responsible drugs (mycophenolic acid [MPA] 51%, valganciclovir 25%, trimethoprim/sulfamethoxazole 19%). Steroids were added/increased as replacement for reduced/discontinued MPA. Granulocyte colony-stimulating factor was only used in 2/357 neutropenia episodes (0.6%). One-year incidence of (sub)clinical rejection, one-year mortality, and long-term patient and graft survival were not different among patients without neutropenia and neutropenia grade 2/3/4. However, the incidence of infections was about 3-times higher during neutropenia grade 3 and 4, but not increased during grade 2. In conclusion, neutropenia within the first year after kidney transplantation represents no increased risk for rejection and has no negative impact on long-term patient and graft survival. Adding/increasing steroids as replacement for reduced/discontinued MPA might supplement management of neutropenia.

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.

Acute kidney injury in patients with COVID-19: a retrospective cohort study from Switzerland.

BACKGROUND: Data about patients in Europe with corona virus disease-2019 (COVID-19) and acute kidney injury (AKI) are scarce. We examined characteristics, presentation and risk factors of AKI in patients hospitalised with COVID-19 in a tertiary hospital in Switzerland. METHODS: We reviewed health records of patients hospitalised with a positive nasopharyngeal polymerase chain reaction test for SARS-CoV2 between 1 February and 30 June 2020, at the University Hospital of Basel. The nadir creatinine of the hospitalisation was used as baseline. AKI was defined according the KDIGO guidelines as a 1.5× increase of baseline creatinine and in-hospital renal recovery as a discharge creatinine <1.25× baseline creatinine. Least absolute shrinkage and selection operator (LASSO) regression was performed to select predictive variables of AKI. Based on this a final model was chosen. RESULTS: Of 188 patients with COVID-19, 41 (22%) developed AKI, and 11 (6%) required renal replacement therapy. AKI developed after a median of 9 days (interquartile range [IQR] 5-12) after the first symptoms and a median of 1 day (IQR 0-5) after hospital admission. The peak AKI stages were stage 1 in 39%, stage 2 in 24% and stage 3 in 37%. A total of 29 (15%) patients were admitted to the intensive care unit and of these 23 (79%) developed AKI. In-hospital renal recovery at discharge was observed in 61% of all AKI episodes. In-hospital mortality was 27% in patients with AKI and 10% in patients without AKI. Age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.01­1.08; p = 0.024), history of chronic kidney disease (aOR 3.47, 95% CI 1.16­10.49;p = 0.026), C-reactive protein levels (aOR 1.09, 95% CI 1.03­1.06; p = 0.002) and creatinine kinase (aOR 1.03, 95% CI 1.01­1.06; p = 0.002) were associated with development of AKI. CONCLUSIONS: AKI is common in hospitalised patients with COVID-19 and more often seen in patients with severe COVID-19 illness. AKI is associated with a high in-hospital mortality.

Screening strategy for de novo donor-specific HLA antibodies beyond the first year after kidney transplantation: Personalized or "one size fits all"?

Screening for de novo donor-specific HLA antibodies (DSAs) after kidney transplantation is widely recommended. The aim of this single-center, cross-sectional study was to investigate the frequency of therapeutic interventions triggered by de novo DSA screening. We included 464 patients screened for de novo DSA at annual visits after a median of 5 years post-transplant (range 1 to 19 years). Overall, de novo DSAs were detected in 55/464 patients (11.9%) with a stepwise increase of the prevalence from 4.9% at 1 year post-transplant to 18.9% at >10 years post-transplant. Subsequent allograft biopsies were performed in 24/55 patients (44%). The main reasons to omit biopsies were good/stable allograft function and anticipated lack of clinical consequences (eg, relevant comorbidities). Rejection processes were detected in 16/24 biopsies (67%). Therapeutic interventions were made in 18/464 screened patients (3.9%) with a significantly higher rate in the youngest quartile of patients (≤48 years; 7.9%) compared to the middle 50% (49-67 years; 3%) and the oldest quartile (≥68 years; 1.7%) (P = .03). Our study suggests that the frequency of therapeutic interventions triggered by de novo DSA screening after kidney transplantation is overall low, but significantly higher in younger patients, arguing for a personalized, age-adapted de novo DSA screening strategy.

First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study.

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, comprehensive data of SARS-CoV-2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS-CoV-2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety-five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow-up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS-CoV-2 infection in middle-aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

EBV-associated mucocutaneous ulcer, a rare cause of a frequent problem.

This report presents a 74-year-old renal transplant patient suffering of polymorphic-post-transplant-associated lymphoproliferative disease (P-PTLD) within an Eppstein-Barr Virus (EBV) associated mucocutaneous rectal ulcer (MCU). He was initially treated by stapled hemorrhoidopexy for a symptomatic grade III hemorrhoidal prolapse refractory to conservative treatment and rubber band ligations. This leads to severe urge, frequency and stool fragmentation. The symptoms were investigated with a number of interventions until a proctoscopy with biopsies finally revealed the diagnosis. The patient had triple therapy of tacrolimus, mycophenolate mofetil and prednisone initially after transplant several years ago with recent reduction to mycophenolate. The MCU was successfully treated with Retuximab and there was no sign of relaps after 6 months. As EBV-associated PTLD is a well known complication after renal transplant, rectum-MCU seems a rare and only recently described subform of this disease that should be excluded in case of ulcerating lesions in immunosuppressed patients.

Revisiting cytomegalovirus serostatus and replication as risk factors for inferior long-term outcomes in the current era of renal transplantation.

BACKGROUND: Cytomegalovirus (CMV) serostatus and CMV replication are considered as risk factors for inferior graft and patient survival after renal transplantation, but long-term outcome data are limited. The aim of this retrospective single-centre study was to investigate the impact of CMV serostatus and CMV replication/disease on long-term outcomes in a well-defined cohort managed by a standardized CMV prevention/treatment protocol. METHODS: We investigated 599 consecutive kidney transplantations having a CMV prevention protocol consisting of either prophylaxis (D+/R- and R+ with ATG induction) or screening/deferred therapy (R+ without ATG induction). Patients were grouped according to CMV serostatus [high risk (D+/R-): n = 122; intermediate risk (R+): n = 306; low risk (D-/R-): n = 171] and occurrence of CMV replication/disease (no CMV replication: n = 419; asymptomatic CMV replication: n = 110; CMV syndrome: n = 39; tissue-invasive CMV disease: n = 31). The median follow-up time was 6.5 years. RESULTS: Graft and patient survival were not different among the three CMV serostatus groups as well as the four CMV replication/disease groups (P ≥ 0.44). Eighty-seven patients died, 17 due to infections (21%), but none was attributable to CMV. The overall hospitalization incidence for CMV-related infection was 3% (17/599 patients). The incidence of clinical and (sub)clinical rejection was similar among the groups (P ≥ 0.17). In a multivariate Cox proportional hazard model, neither CMV serostatus, nor CMV replication, nor CMV disease were independent predictors for patient death or graft failure, respectively. CONCLUSIONS: This retrospective single-centre study suggests that the negative impact of CMV infection on long-term patient and allograft survival as well as on allograft rejection can be largely eliminated with current diagnostic/therapeutic management.

Daratumumab for Treatment of Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation.

We report the effectiveness of daratumumab, a human IgGκ monoclonal antibody targeting CD38 on plasma cells, for therapy-refractory antibody-mediated rejection (AMR) due to blood group antibodies in a 59-year-old man who received a living ABO-incompatible kidney transplantation. Standard treatment options for AMR due to blood group antibodies including immunoadsorption, lymphocyte depletion with anti-human T-lymphocyte globulins, intravenous methylprednisolone pulses and eculizumab limited tissue injury, however failed to sufficiently suppress blood group antibody production. After administration of daratumumab as a rescue therapy, blood group antibody titers decreased and remained at low levels without further immunoadsorption and allowed kidney graft function to recover.

Differential Impact of Delayed Graft Function in Deceased Donor Renal Transplant Recipients With and Without Donor-specific HLA-antibodies.

BACKGROUND: Delayed graft function (DGF) and pretransplant donor-specific HLA-antibodies (DSA) are both regarded as risk factors for rejection and lower graft survival. However, the combined impact of DGF and DSA has not been studied in detail. METHODS: We investigated 375 deceased donor kidney transplantations, which had DSA assignment by single-antigen bead technology and which had surveillance biopsies at 3 of 6 months. Median follow-up time was 6.1 years. RESULTS: DGF occurred in 137 of 375 patients (37%), and DSA were present in 85 of 375 patients (23%). The incidence of DGF was similar in DSA-positive (DSApos)-patients and DSA-negative (DSAneg)-patients (40% versus 36%; P = 0.45). In DSAneg-patients, 5-year graft survival was not different with/without DGF (81% versus 83%; P = 0.48). By contrast, in DSApos-patients, 5-year graft survival was significantly lower with DGF (64% versus 79%; P = 0.01). Moreover, DSApos-patients with DGF had a higher 1-year incidence of subclinical rejection, which were mostly antibody-mediated or mixed rejection phenotypes. Graft loss due to rejection was significantly more frequent in DSApos-patients with DGF (5/34; 15%) compared to DSApos-patients without DGF (2/51; 4%), and DSAneg-patients with/without DGF (3/103; 3% and 4/187; 2%, respectively) (P = 0.005). In a multivariate Cox model, DSA with DGF was an independent predictor for graft (hazard ratio = 2.84 [95% confidence interval, 1.54-5.06]; P = 0.001) and death-censored graft loss (hazard ratio = 4.65 [95% confidence interval, 1.83-11.51]; P = 0.002). CONCLUSIONS: DGF has a much more detrimental impact in DSApos-patients than in DSAneg-patients, which is likely related to a higher incidence of antibody-mediated rejection. If possible, the combined risks of DGF and DSA should be avoided.