Sepsis after renal transplantation: Clinical, immunological, and microbiological risk factors

Abstract

Background: As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease-free survival after renal transplantation.

Methods: We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. In all, 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV-specific and alloreactive T cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations.

Results: Five-year patient survival was 70.3% with sepsis compared to 88.2% without (P<.001). Five-year estimated glomerular filtration rate was lower in KTRs developing sepsis (P<.001). Upon multivariate analysis, diabetes, lymphocyte-depleting induction, donor age, CMV replication, and acute rejection increased the risk of sepsis (P<.05). Age, diabetes, underweight/obesity, and pneumonia as site of infection were predictive factors of mortality (P<.05). Early-onset sepsis was associated with decreased CD3+ and CD4+ T cells pre-transplantation (P<.05). Impaired CMV-specific cellular immunity pre-transplantation was associated with CMV replication and early-onset sepsis (P<.05). High frequencies of alloreactive T cells were associated with acute rejection, lymphocyte-depleting rejection treatment, and early-onset sepsis (P<.05).

Conclusion: KTRs developing sepsis show inferior patient survival and allograft function. Identified risk factors and differences in lymphocyte counts, CMV-specific immunity, and alloreactivity may prove useful to identify KTRs at increased risk.

Keywords: CMV; T cells; alloreactivity; renal transplantation; sepsis.