Kidney transplant recipients (KTRs) are extremely vulnerable to SARS‐CoV‐2 infection and show an impaired immune response to SARS‐CoV‐2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS‐CoV‐2 spike S1 subunit and their neutralization capacity after SARS‐CoV‐2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78–519] BAU/ml versus 1826 [560–3180] BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF‐free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22–54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R −0.354, p < .001) supporting a dose‐dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.

Background: Kidney failure patients on dialysis or after renal transplantation have a high risk for severe COVID-19 infection and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in kidney failure patients, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in dialysis patients and in kidney transplant recipients (KTR) are still missing. Methods: In this prospective multicentric cohort study, antibody responses COVID-19 mRNA vaccines (BNT162b2; Biontech/Pfizer or mRNA-1273; Moderna) were measured in 32 dialysis patients and in 28 KTRs. SARS-CoV-2-specific antibodies and neutralization capacity were evaluated and compared to controls (n=78) in a similar age-range. Results: After the first vaccination, SARS-CoV-2-specific antibodies were nearly undetectable in kidney failure patients. After the second vaccination, 93% of the controls and 88% of dialysis patients but only 37% of KTRs developed SARS-CoV-2-specific IgG above cut-off. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared to dialysis patients (503±481 BAU/ml, p<0.01). Both KTRs as well as dialysis patients had significantly lower IgG levels compared to controls (1992±2485 BAU/ml; p<0.001 and p<0.01). Importantly, compared to controls, neutralizing antibody titers were significantly lower in KTRs and dialysis patients. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2 suggesting impaired seroprotection. Conclusions: Kidney failure patients show a significantly weaker antibody response compared to controls. Most strikingly, only one out four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in immune transplant and dialysis patients.

Modification of vaccination strategies is necessary to improve the immune response to SARS‐CoV‐2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the effects of the third SARS‐CoV‐2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion ( P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2–2.5) μg/ml and were more likely to seroconvert than matched controls ( P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS‐CoV‐2 vaccination in KTRs.

Background: Modification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). Methods: This multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success. Results: 18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels (<≤>206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76-353) BAU/ml and median neutralizing capacity titer of 1:10 (0-1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09-1.76), graft function (OR 0.05, 95% CI 0.01-0.39), time after transplantation (OR 1.04, 95% CI 1.02-1.07) and MMF trough levels (OR 0.43, 95% CI 0.21-0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels <≥>35.2 BAU/ml than their matched KTRs (p=0.02). Conclusions: Temporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.

Patients with primary aldosteronism (PA) are more susceptible to cardiovascular disease and mortality than patients with primary hypertension. This is mostly attributed to excess production of aldosterone and its effects on the development of vascular injury. A novel functional test (T50) measures serum calcification propensity. Lower T50-values predict higher cardiovascular risk. We investigated serum calcification propensity and vascular calcification in PA and resistant hypertension (RH). T50 measurement was performed in patients with PA (n = 66) and RH (n = 28) at baseline and after 403 (279–640) and 389 (277–527) days of treatment. No significant differences in T50-values were observed between the groups (371 ± 65 and 382 ± 44 min, in PA and RH group, respectively, p &gt; 0.05). However, higher aldosterone-to-renin ratios were associated with lower T50-values in PA-patients (r −0.282, p &lt; 0.05). Furthermore, lower T50-values were associated with increased abdominal aortic calcification measured by Agatston score in PA (r −0.534, p &lt; 0.05). In both, PA and RH, higher atherosclerotic cardiovascular disease (ACSVD) scores (r −0.403, p &lt; 0.05) and lower HDL (r 0.469, p &lt; 0.05) was related to lower T50-values in a linear regression model. Adrenalectomy or medical treatment did not increase T50-values. In comparison to patients with stable T50-values, PA patients with a decrease in T50 after intervention had higher serum calcium concentrations at baseline (2.24 ± 0.11 vs. 2.37 ± 0.10 mmol/l, p &lt; 0.05). This decline of T50-values at follow-up was also associated with a decrease in serum magnesium (−0.03 ± 0.03 mmol/l, p &lt; 0.05) and an increase in phosphate concentrations (0.11 ± 0.11 mmol/l, p &lt; 0.05). Resistant hypertension patients with a decrease in T50-values at follow-up had a significantly lower eGFR at baseline. In summary, these data demonstrate an association between a high aldosterone-to-renin ratio and low T50-values in PA. Moreover, lower T50-values are associated with higher ACSVD scores and more pronounced vascular calcification in PA. Thus, serum calcification propensity may be a novel modifiable risk factor in PA.

Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

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Zusammenfassung Anamnese Wir berichten über einen 57-jährigen Patienten, der in unserer Klinik zur geplanten AB0-inkompatiblen Lebendnierentransplantation aufgenommen wurde. Untersuchungen und Diagnose An Tag 3 post operationem bildeten sich laborchemisch eindeutige Hinweise für eine De-novo-TMA aus. Die renale Entgiftung stagnierte bei initialem regelrechtem Verlauf. Therapie und Verlauf Durch den Einsatz von Eculizumab 900 mg an d3 und d10 post operationem konnten wir die TMA mit einem anhaltenden Erfolg unterbinden. Folgerung Zu diskutieren ist, ob ein frühzeitiger Einsatz von Eculizumab bei V. a. De-novo-TMA ein sicherer Weg ist, eine Transplantatdysfunktion zu unterbinden und somit die in der Literatur beschriebene schlechte Prognose für Transplantat und Empfänger zu verbessern.