Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth, and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased the serological response rate to 75% in comparison to the no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.
Background. Early haemodynamic assessment is of particular importance in the evaluation of haemodynamically compromised patients, but is often precluded by the invasiveness and complexity of the established cardiac output (CO) monitoring techniques. The FloTrac TM /Vigileo TM system allows minimally invasive CO determination based on the arterial pressure waveform derived from any standard arterial catheter, and the algorithm underlying CO calculation was recently modified to allow a more precise estimate of aortic compliance.Methods. Using the new software, we studied 25 haemodynamically unstable patients who had a radial artery catheter and underwent invasive haemodynamic monitoring with the PiCCO TM system. PiCCO TM -derived transpulmonary thermodilution and pulse contour CO (reference-CO) were compared with the CO values obtained with the FloTrac TM /Vigileo TM system (AP-CO). Reported CO values are indexed to body surface area. Agreement between reference-CO and AP-CO recorded during routine clinical care was assessed using Bland -Altman statistics.Results. Overall bias between the reference-CO and the AP-CO (n¼324) was 0.68 litre min 21 m 22 with a high percentage error of +58.8% (95% limits of agreement +1.94 l min 21 m 22 ). There was a significant difference (P,0.001) between the radial and the femoral mean arterial pressures, and bias was significantly larger for a mean pressure difference of .5 mm Hg (0.93 vs 0.57 litre min 21 m 22 , P¼0.032). No connection was found between the norepinephrine dose and the CO agreement.Conclusions. Despite the updated algorithm, AP-CO still showed a limited agreement with the reference-CO and systematically underestimated the CO so that the method is not suitable to replace invasive CO monitoring at present.
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