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Cryptococcosis is a frequent invasive fungal infection in solid organ transplant (SOT) recipients, being the third most frequent invasive mycosis. Worldwide prevalence is 5-10% and the incidence is 0.2 to 5%. The median time onset in all organ transplants is usually 16 to 21 post transplant-months. However, the time of onset in kidney transplant recipients is later.
We retrospectively assessed the prevalence of cryptococcosis in kidney transplant patients at Hospital Italiano de Buenos Aires (Argentina) between 1988 and 2023. We analyzed the following variables: age, sex, type of transplant, lymphopenia, immunosuppressive induction treatment, rejection and treatment.
A total of 951 patients received a kidney transplant, 168 received a combined kidney-pancreas, 43 received a liver-kidney transplant and 15 received a heart-kidney transplant between 1988 and 2023. Of these, 25 (2.6%) patients had developed cryptococcosis (Cs), 56% were females. All had dialyzed before transplantation (median of 39 months) and 68.2% had received immunosuppression before transplantation due to glomerulonephritis or prior transplant (thymoglobulin, cyclophosphamide, steroids and/or rituximab). 22 out of 25 patients were isolated kidney transplant (Cs prevalence 2.31%), 2 simultaneous liver-kidney transplants (Cs prevalence 4.65%) and 1 simultaneous pancreas-kidney transplant (Cs prevalence 0.59%). 64% received kidneys from deceased donors. 3 patients had had a previous transplant. The median onset of cryptococcosis was 35 months, with a higher proportion of cases in the first 50 months. Meningeal was the main localization (36%). 52% of patients presented disseminated disease. Mean total lymphocytes count at time of diagnosis was 710 cells/mm3. A total of 4 deaths (16%) were vinculated to cryptococcosis. Thymoglobulin was used as induction therapy in 82.6% of cases (median 6.5 mg/kg IQR 4.250 - 7.75 mg/kg). 40% of patients had been treated for rejection within a year before the development of cryptococcosis.
All patients received immunosuppression with triple therapy: steroids, calcineurin inhibitors and mycophenolic acid . Only 3 patients developed cryptococcosis in between 1988 and 2015 (period 1) (0.11 cases/year). After 2015, in coincidence with development of new diagnostic tools for acute AMR (Antibody Mediated Rejection) and the consequent increase of burden immunosuppressive therapy, 22 patients had cryptococcosis (2.75 cases/year). This reflects a higher Cs prevalence in kidney transplants between periods: 0.051% in period 1 vs 5.09% in period 2 (p < 0.0001).
In this population we observed in the last years an increased incidence in cs infection in kidney transplant patients. This increase seems to be due to a higher dose of immunosuppression.