RESUMO
Background: There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of allograft rejection with that of infections and malignancy. At our center, KTRs are managed with either a "preemptive" dose reduction strategy, where the MMF dose is reduced after the first year before the development of adverse events, or with a "reactive" dosing strategy, where they are maintained on the same MMF dose and only reduced if they develop an adverse event. We hypothesized that a preemptive MMF dosing strategy after the first year of transplantation is associated with decreased infections without increasing alloimmune complications. Methods: We conducted a retrospective cohort study of all KTRs receiving MMF from January 1, 2015, to December 31, 2020. The primary outcome was the incidence of infections requiring hospitalization. Results: One hundred forty-two KTRs met the inclusion criteria, of whom 44 (31%) were in the preemptive group and 98 (69%) were in the reactive group. The median follow-up was 4 y (interquartile range, 3.8-4.0). Multivariable analysis showed that a preemptive MMF dose reduction strategy was associated with a lower risk of infections requiring hospitalization (adjusted hazard ratio = 0.39; 95% confidence interval, 0.16-0.92). There was no difference in graft loss, rejection, or estimated glomerular filtration rate slope. Conclusions: Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection. Randomized clinical trials are needed to confirm these findings.
RESUMO
Introduction: Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited. Materials and methods: To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2. Results: At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.