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Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

Introduction and Aims: Various programs of physical exercise have been shown to improve outcomes in hemodialysis (HD) patients. Increasing age and comorbidity, however, are perceived to limit options for therapeutic exercise on HD. An individually structured physical exercise program (SPEP), broadly applicable also for frail and elderly patients, was introduced in five units of a large non-profit provider. We compared outcomes in SPEP patients with propensity-score (PS) matched controls. Methods: Patients ( pts) were offered a supervised SPEP consisting of 30 mins. each of strength-and endurance training twice weekly. Data were collected prospectively from the electronic health records through a quality registry. Controls were selected based on a PS including age, sex, vascular access, albumin and 16 other variables. Outcomes assessed were survival and hospitalization rate. Results: 98 pts participated in the SPEP and were matched with 490 controls (mean age: 68.6 yrs (IQR 58-78), mean vintage 56.4 mo (SD 55.0), 45.4% female, 51.4% diabetic, 33.7% with PVD). 17.9% were > 80 years old, 10.5% had a baseline albumin of < 35g/l, 45.7% had > 4 co-morbidities, 78.4% had permanent contra-indications to transplantation. After one year of training, important outcome-associated parameters improved in SPEP pts. but not in controls. Hemoglobin increased 1.3 % (0.15 g/dl, p = n.s.), and serum anorganic phosphate decreased 1.8 % (0.03 mmol/l, p = 0.04). Survival at one year was higher in SPEP-pts than in controls ( p=n.s.), and hospitalizations were lower ( p=0.03). Conclusions: These results confirmed that improving strength and endurance by exercise while dialyzing was not only associated with improved surrogate markers but decreased hospitalizations and, possibly, mortality. Individualized training was feasible also in elderly and frail HD patients. This will likely translate into improved patients' well-being, care perception, and fall prevention. This SPEP, therefore, should be considered as a non-pharmaceutical and patient-centered routine part of hemodialysis treatment.

Background and Aims SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis (DP) and kidney transplant patients (KTR). Recently, we demonstrated that established vaccination related immunity (via positive seroconversion) fades faster in DP and at a lesser extent in KTR compared to medical personnel (MP).[1] We hypothesized that a longer follow up period might be able to profoundly show immunity fading differences specific to different patient groups and identify strong fading risk factors that are relevant for patient management especially in vulnerable groups. Method We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy MP (125), DP (595), KTR (111), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Results Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time (see Fig. 1 and Table 1). By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. Conclusion While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.

Background and Aims Immunity development and fading after SARS-CoV-2mRNA vaccination differently affects high risk populations such as dialysis or renal transplant patients compared to general population. We hypothesized that COVID-19 preexposure influences not only vaccination dependent development of immunity but also protects from immunity fading depending on vaccine type and patient group. Method We evaluated two and nine months follow up data in our observational DIA-Vacc study exploring specific cellular (interferon-γ release assay = IGRA) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 2615 participants including medical personnel (300 MP), dialysis patients (1831 DP), kidney transplant recipients (484 KTR). Study participants were separated into COVID-19 preexposure positive (n = 405) versus negative (n = 2210) groups, where symptomatic or asymptomatic COVID-19 disease before start of vaccination was confirmed by clinical symptoms, PCR positivity and/or Spike S1/core antiSARS-CoV-2 antibodies. Results Two months (T2) after first vaccination, seroconversion and T-cell immunity success rates for MP and DP were excellent (86-100%) and independent on COVID-preexposure. In KTR, vaccination-related seroconversion rate on T2 almost doubled with COVID-preexposure (84% versus 45% without), a result consistent with all different antibody measurements (IgA, IgG, or receptor binding domain-RBD). Nine months after first vaccination in COVID-19 negative study patients, the percentage of patients with RBD-antibody fading results &gt;50% remained low in MP (18%), high in DP (53%) and intermediate in KTR (39%). In contrast, in all patient groups with COVID-19 preexposure RBD-antibody fading reactions &gt;50% within nine months after vaccination were almost vanished (4% in MP, 8% in DP and 0% in KTR). COVID-19 preexposure in DP also reduced T-cell immunity fading as measured by IGRA, where only 9% of patients showed a &gt;50% titer decrease compared to 34% of DP without any COVID-19 preexposure. Similar results were also seen regarding vaccination dependent regulation of antiSARS-Cov-2 IgG antibodies dependent on COVID-19 preexposure. These results are also reflected by increased mean antibody titers for IgG- and RBD-antibodies nine months after vaccination in all COVID-19 preexposed compared to non-exposed groups. In addition, the degree of antibody fading after vaccination was not just dependent on COVID-19 preexposure status but also on mRNA vaccine type being used. In MP with COVID-preexposure, 22% of BNT162b2mRNA but 0% of 1273-mRNA vaccinated study participants experienced RBD-antibody fading &gt;50% within nine months after vaccination start. This significant difference was even greater in COVID-19 preexposed DP, in whom vaccination with BNT162b2mRNA caused RBD-antibody fading &gt;50% in 36% compared to 6% of 1273-mRNA treated DP. The patient number in the KTR group was not high enough for a vaccine type comparison. This vaccine dependent influence on antibody fading is consistent with our results in patient groups without COVID-19 preexposure. Conclusion Long term immunity time course is markedly modified via COVID-preexposure in a mRNA vaccine dependent matter. Hybrid immunity after COVID-19 preexposure almost completely lacks immunity fading between two and nine months especially in 1273-mRNA vaccinated MP, DP, or KTR. Immune monitoring shows great individual variability dependent on personal patient history and should be especially used for pandemic patient management in vulnerable groups such as DP and KTR.