Predicting Kidney Transplantation Outcomes from Donor and Recipient Characteristics at Time Zero: Development of a Mobile Application for Nephrologists.

(1) Background: We report on the development of a predictive tool that can estimate kidney transplant survival at time zero. (2) Methods: This was an observational, retrospective study including 5078 transplants. Death-censored graft and patient survivals were calculated. (3) Results: Graft loss was associated with donor age (hazard ratio [HR], 1.021, 95% confidence interval [CI] 1.018-1.024, p < 0.001), uncontrolled donation after circulatory death (DCD) (HR 1.576, 95% CI 1.241-2.047, p < 0.001) and controlled DCD (HR 1.567, 95% CI 1.372-1.812, p < 0.001), panel reactive antibody percentage (HR 1.009, 95% CI 1.007-1.011, p < 0.001), and previous transplants (HR 1.494, 95% CI 1.367-1.634, p < 0.001). Patient survival was associated with recipient age (> 60 years, HR 5.507, 95% CI 4.524-6.704, p < 0.001 vs. < 40 years), donor age (HR 1.019, 95% CI 1.016-1.023, p < 0.001), dialysis vintage (HR 1.0000263, 95% CI 1.000225-1.000301, p < 0.01), and male sex (HR 1.229, 95% CI 1.135-1.332, p < 0.001). The C-statistics for graft and patient survival were 0.666 (95% CI: 0.646, 0.686) and 0.726 (95% CI: 0.710-0.742), respectively. (4) Conclusions: We developed a mobile app to estimate survival at time zero, which can guide decisions for organ allocation.

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients.

Introduction: Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. Methods: To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. Results: Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. Discussion: In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study.

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P < .001) with similar Cmin and 30% lower TDD levels (P < .0001). The incidence of treatment failure was 3.9% in the LCPT group and 9.0% in the PR-Tac group (P = .117). Study discontinuation rates were 6.2% in the LCPT group and 12.4% in the PR-Tac group (P = .113). Adverse events, renal function and other complications were comparable between groups. The median accumulated dose of tacrolimus in the LCPT group from day 14 to month 6 was 889 mg. Compared to PR-Tac, LCPT showed higher relative bioavailability, similar effectiveness at preventing allograft rejection, comparable effect on renal function, safety, adherence, treatment failure and premature discontinuation rates.

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.