COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

SARS-CoV2 mRNA Vaccine-Specific B-, T- and Humoral Responses in Adolescents After Kidney Transplantation.

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12-18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 ("Comirnaty"; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults.

Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring.

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.

Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients.

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.

Time-dependent effects of cadaveric renal transplantation on arterial compliance in patients with end-stage renal disease.

BACKGROUND: Cardiovascular complications are the leading cause of mortality in patients undergoing hemodialysis. Increased arterial stiffness is a strong and independent predictor of cardiovascular risk in these patients. In the present study, we investigated the time-dependent effects of cadaveric renal transplantation on arterial elasticity in end-stage renal disease patients. METHODS: Thirty-six patients underwent successful cadaveric kidney transplantation. Pulse-wave analysis of the radial artery was performed prior to transplantation (day 0) and at six defined intervals after transplantation (day 1 to 90). Compliance of large conduit arteries (C1) and of small resistance arteries (C2) was assessed using a modified Windkessel model of the circulation. RESULTS: Both large artery and small artery compliance were transiently improved within the first four weeks posttransplant reaching a maximum of 122 +/- 42% (C1) and 147 +/- 93% (C2) between day 19 and 23. After the first month, however, elasticity gradually deteriorated to reach baseline values three months after transplantation again. CONCLUSION: The benefits of cadaveric renal transplantation on oscillatory and capacitive artery compliance are only transient. It may be speculated that the subacute and long-term vasoactive effects of calcineurin inhibitors counteract the metabolic benefits of increased renal function on the vasculature.

Convenience of ambulatory blood pressure monitoring: comparison of different devices.

OBJECTIVE: Twenty-four-hour ambulatory blood pressure monitoring has emerged as an important tool supporting physicians in the diagnosis and management of arterial hypertension. Compared with office measurements and self-measurements, however, ambulatory blood pressure monitoring shows the lowest patients' acceptance. The present study compares the convenience of different monitors in order to examine whether the patients benefit from new technologies. METHODS: In a prospective randomized study, we compared the side effects of the Spacelabs 90207 with the I.E.M. Mobilograph monitor in 250 patients by means of a questionnaire that covered the following aspects: restriction in everyday activities, noise, sleep disturbance, pain and mobility. Complaints were measured by a five-point scale ranging from 'no complaints at all' to 'severe complaints'. RESULTS: In all, 205 patients returned completed surveys (101 patients of the I.E.M. group, 104 patients of the Spacelabs group), yielding an 82% final response rate. The overall mean complaint score was significantly higher in the Spacelabs group than in the I.E.M group (2.24 vs. 1.78; P<0.001). The Mobilograph revealed less discomfort in every single question and differences were significant for restrictions in everyday activities, noise, pain, disturbance of the patient's or the patient's partner's sleep and restrictions in walking. Sleep disturbance was the aspect with the highest difference in the two groups. CONCLUSION: The present work confirms that ambulatory blood pressure monitoring monitors are cumbersome to wear. Devices, however, differ in their comfort. Monitors with an improved convenience might lead to a higher patients' acceptance of this powerful diagnostic tool.