Immunosuppressive therapy management during sepsis in kidney transplant recipients: a prospective multicenter study

Sepsis is the leading cause of Intensive Care Unit (ICU) admissions in kidney transplant recipients (KTRs). However, the optimal immunosuppressive therapy (IST) management in this context is not well-defined. We aimed to evaluate the impact of IST management in the ICU on mortality rates and kidney graft function 6 months after inclusion in KTRs admitted for sepsis.

We conducted a multicenter, prospective, observational study over 1 year in 11 French ICUs. Inclusion criteria were all KTRs who have been transplanted for at least 3 months, admitted to the ICU for sepsis. All changes of IST (7 days prior to ICU admission or throughout the ICU stay) were collected. The primary outcome was MAKE 180 (Major Adverse Kidney Event), a composite outcome including mortality, kidney graft dysfunction and dialysis requirement at 180 days after inclusion.

One hundred and twenty-four patients were included. The main cause of ICU admission was respiratory failure for 78 patients (62.9%). Predominant IST management was mycophenolic acid (MPA) discontinuation for 74 patients (59.7%) and calcineurin inhibitor (CNI) continuation for 63 patients (50.8%). By multivariable analysis, after adjustment for age, non-renal SOFA score at admission, kidney function at admission, sex, and history of cellular rejection we did not find any significant association between MAKE 180 and CNI discontinuation (adjusted OR = 1.05, 95% CI 0.87-1.26, p = 0.6). In contrast, MPA discontinuation was significantly associated with MAKE 180 (adjusted OR = 1.45, 95% CI 1.07-1.96, p = 0.018). No significant association was found between IST discontinuation and ICU-acquired infections (adjusted OR = 1.14, 95% CI 0.95-1.36, p = 0.157). Among ICU survivors, only 2 graft rejections occurred during the year following ICU discharge.

This study is the first prospective investigation to suggest an association between MPA discontinuation and adverse outcomes during sepsis in critically-ill KTRs. These findings must be interpreted with caution given the potential confounding introduced by SARS-Cov-2-specific treatment protocols. Further interventional trials are necessary to optimize immunosuppressive drug strategies in KTRs during sepsis.