Humoral Immune Response to SARS-CoV-2 Vaccination after a Booster Vaccine Dose in Two Kidney Transplant Recipients with Fabry Disease and Variable Secondary Immunosuppressive Regimens

The urgent need to fight the COVID-19 pandemic has accelerated the development of vaccines against SARS-CoV-2 and approval processes. Initial analysis of two-dose regimens with mRNA vaccines reported up to 95% efficacy against the original strain of the SARS-CoV-2 virus. Challenges arose with the appearance of new strains of the virus, and reports that solid organ transplant recipients may have reduced vaccination success rates after a two-dose mRNA vaccination regimen encouraged health authorities to recommend a booster in immunocompromised patients. Fabry disease is an X-linked inherited lysosomal disorder, which may lead to chronic end-stage renal disease. We report on two patients with advanced Fabry disease, renal graft and adjunctive immunosuppressive therapies who exhibited variable humoral vaccination-related immune responses against SARS-CoV-2 after three vaccine doses. The first patient developed mild COVID-19 infection, while the second patient did not seroconvert after three shots of an mRNA vaccine. Both cases emphasize that patients with Fabry disease and renal graft are susceptible to develop a weak response to COVID-19 vaccination and highlight the importance of maintaining barrier protection measures. Vaccination of family members should be encouraged to lower the risk of viral transmission to immunocompromised, transplanted patients, including vaccinated ones.

IMMUNOLOGICAL PREDICTORS OF RENAL GRAFT REJECTION IN THE EARLY POSTOPERATIVE PERIOD

Objective. To determine the immunological predictors of renal graft rejection in the early postoperative period. Methods. Three groups were formed out of the 197 renal graft recipients. The group PGF (n=101) was made up of patients with satisfactory primary graft function. The group PGD (n = 82) included patients with primary graft dysfunction without episodes of rejection. The group RGR (n=14) consisted of patients with primary dysfunction and renal graft rejection. On the 7^th day after transplantation the early kidney graft function was assessed on the basis ofserum creatinine levels. When the serum creatinine value was lower than 300 μmol/L the function was considered to be primary, at a creatinine concentration was equal to or higher than 300 μmol/L, as well as in the case of needfor maintenance dialysis on the first week after transplantation, the state was classified as the renal graft dysfunction. In the early postoperative period, the number of LIN-HLA-DR+ dendritic cells with the LIN-HLA-DR+CD11c+CD123- and LIN-HLA-DR+CD11c-CD123+ phenotypes in the fluid from the drainage installed to the kidney graft during surgery was determined. Predictive characteristics of the mDC and pDC levels in the drainage fluid were determined to predict renal graft rejection, and diagnostic capability of this indicator were identified. Results. It has been revealed that renal graft rejection is characterized by a significant growth of the total number of dendritic cells in the drainage fluid, mainly due to myeloid ones. Predictive characteristics were determined by the level of myeloid and plasmacytoid dendritic cells in the drainage fluid. The cut-off point of the level of myeloid dendritic cells was determined at the level of 60.32%, and for plasmacytoid dendritic cells it corresponded to 39.68%. Conclusion. With the level of myeloid dendritic cells in the drainage fluid greater or equal 60.32%, and plasmacytoid cells lower or equal 39.68%, renal graft rejection is predicted with a sensitivity of 99% and 93%, respectively, and a specificity of 89% and 91%, respectively. What this paper adds The level of dendritic cells and their subpopulations in the drainage fluid in renal graft recipients has been firstly studied. It has been established that acute renal graft rejection is associated with a high concentration of the total number of dendritic cells in the drainage fluid. More over this increase occurs mainly due to myeloid dendritic cells. The determination of the level of myeloid and plasmacytoid dendritic cells in the drainage fluid can be used as a predictor of renal graft rejection.

Simultaneous heart-kidney transplantation results in respectable long-term outcome but a high rate of early kidney graft loss in high-risk recipients – a European single center analysis

Background In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. Methods This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe’s largest transplant centers. Results Median follow-up was 100.33 (0.46–362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). Conclusions Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a “kidney-after-heart” program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.