Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression

Background: Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined.

Methods: SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria.

Results: Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07).

Conclusions: We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.