Cryptococcosis in kidney transplant recipients: Current understanding and practices

Abstract

Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.

Keywords: Cryptococcosis; Kidney transplant recipients; Amphotericin B; Immunosuppression; Fluconazole

Core Tip: Cryptococcosis is the third most common invasive fungal infection in solid organ transplant recipients. As an opportunistic infection, it poses substantial morbidity and mortality in kidney transplant recipients. Mortality rates for cryptococcosis range from 10% to 25%. In immunocompromised patients, especially in cryptococcus-endemic areas, cryptococcosis must be suspected and diagnosed with a low threshold. Compared to India ink and fungal cultures, tests for the cryptococcal antigen detection in cerebrospinal fluid or plasma test are more sensitive and specific. The management of cryptococcosis poses considerable difficulties, mostly done with reduction or optimization of immunosuppression in addition to lipid formulations of amphotericin B and fluconazole.