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Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.

Budde K (2022) The natural history of de novo donor-specific HLA antibodies after kidney transplantation.

Immunosuppression withdrawal after graft failure seems to favor sensitization. A high percentage of calculated panel-reactive antibody (cPRA) and the development of de novo donor specific antibodies (dnDSA) indicate human leukocyte antigen (HLA) sensitization and may hinder the option of retransplantation. There are no established protocols on the immunosuppressive treatment that should be maintained after transplant failure. A retrospective analysis including 77 patients who lost their first renal graft between 1 January 2006–31 December 2015 was performed. Two sera were selected per patient, one immediately prior to graft loss and another one after graft failure. cPRA was calculated by Single Antigen in all patients. It was possible to analyze the development of dnDSA in 73 patients. By multivariate logistic regression analysis, the absence of calcineurin inhibitor (CNI) at 6 months after graft failure was related to cPRA > 75% (OR 4.8, CI 95% 1.5–15.0, p = 0.006). The absence of calcineurin inhibitor (CNI) at 6 months after graft loss was significantly associated with dnDSA development (OR 23.2, CI 95% 5.3–100.6, p < 0.001). Our results suggest that the absence of CNI at the sixth month after graft loss is a risk factor for sensitization. Therefore, maintenance of an immunosuppressive regimen based on CNI after transplant failure should be considered when a new transplant is planned, since it seems to prevent HLA allosensitization.

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49–16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2–8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65–11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.

No abstract

The Banff 2017 report permits the diagnosis of pure chronic antibody-mediated rejection (cAMR) in absence of microcirculation inflammation. We retrospectively investigated renal allograft function and long-term outcomes of 67 patients with cAMR, and compared patients who received antihumoral therapy (cAMR-AHT, n = 21) with patients without treatment (cAMRwo, n = 46). At baseline, the cAMR-AHT group had more concomitant T-cell-mediated rejection (9/46 (19.2%) vs. 10/21 (47.6%); p = 0.04), a higher g-lesion score (0.4 ± 0.5 versus 0.1 ± 0.3; p = 0.01) and a higher median eGFR decline in the six months prior to biopsy (6.6 vs. 3.0 mL/min; p = 0.04). The median eGFR decline six months after biopsy was comparable (2.6 vs. 4.9 mL/min, p = 0.61) between both groups, and three-year graft survival after biopsy was statistically lower in the cAMR-AHT group (35.0% vs. 61.0%, p = 0.03). Patients who received AHT had more infections (0.38 vs. 0.20 infections/patient; p = 0.04). Currently, antihumoral therapy is more often administered to patients with cAMR and rapidly deteriorating renal function or concomitant TCMR. However, long-term graft outcomes remain poor, despite treatment.

BackgroundTransplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated.Methods282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT).ResultsUp to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (−3.0 vs. −2.0 vs. −2.8 ml/min/1.73 m2 per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m2), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure.ConclusionsThe occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.