Allograft Loss in Renal Transplant Recipients with Cryptococcus Neoformans Associated Immune Reconstitution Syndrome

Abstract

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans

“…Patients were recruited as part of an ongoing study of C. neoformans infection in organ transplant patients (57). Briefly, patients undergoing solid organ transplant who had a cryptococcal isolate from sterile fluid and a confirmatory positive cryptococcal antigen were recruited from the University of Pittsburgh Medical Center.…”

Cryptococcosis

“…Drug interactions between fluconazole and immunosuppressive agents should be anticipated due to fluconazole-induced CYP3A4 inhibition, and preemptive adjustment (reduction) in calcineurin inhibitors should be made. Management of immunosuppression in the setting of cryptococcal infection requires recognition of the increased risk of IRIS associated with abrupt withdrawal or reduction of immunosuppression in organ transplant recipients with increased rates of allograft loss reported in some patients [95][96][97]. Stepwise reduction in immunosuppression is recommended, though the approach should be individualized for each patient.…”

“…Proposed criteria for IRIS include onset of symptoms within 12 months of HAART initiation (with concomitant CD4 + recovery) [109]. In addition, IRIS is estimated to occur in 5-11 % of SOT recipients with cryptococcal infection and has been associated with an increased risk of allograft failure [95,[110][111][112][113][114]; cryptococcal IRIS may also be observed in non-HIV-infected, nontransplant patients [115].…”

Cellulitis Revealing a Cryptococcosis-Related Immune Reconstitution Inflammatory Syndrome in a Renal Allograft Recipient

“…Renal transplant recipients with cryptococcosis-related IRIS are more likely to experience graft rejection and/or loss, which occurred in up to 66% in a recent series (9). Corticosteroid therapy has been successful for the control of cryptococcosis-related IRIS in HIV patients (5).…”

“…neoformans-associated IRIS has mostly been described in HIV-infected patients under highly active antiretroviral therapy (HAART) (5,8). C. neoformans-associated IRIS has also been described in solid organ transplant patients, with an estimated incidence of 4.8% in all SOT recipients (6) and 5.5% in the subpopulation of renal transplant recipients (9), and usually occurred shortly after antifungal treatment's initiation. C. neoformans-associated IRIS has also been described after recovery from alemtuzumab therapy for T-cell prolymphocytic leukaemia (10).…”