Hyponatremia as an indicator of central nervous system cryptococcosis in renal transplant recipients

A report of two cases.

Abstract

Introduction: Cryptococcosis is a major invasive fungal infection in kidney transplant recipients and is associated with high morbidity and mortality, particularly when it involves the central nervous system. Its clinical presentation is often nonspecific, which can delay diagnosis. Evidence regarding the association between hyponatremia and central nervous system cryptococcosis in this population is limited.

Materials and methods: A retrospective study of two cases of central nervous system cryptococcosis in kidney transplant recipients with hyponatremia. Demographic variables, transplant characteristics, immunosuppression regimens, clinical presentation, biochemical and microbiological findings, antifungal treatment, and clinical outcomes were analyzed.

Results: Two cases of late-onset central nervous system cryptococcosis were documented, diagnosed 6 and 12 years after kidney transplantation. The patients were receiving maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone. Both presented with neurological manifestations associated with hyponatremia upon admission. Diagnosis was confirmed via multiplex PCR of cerebrospinal fluid, direct examination with India ink, and isolation of *Cryptococcus neoformans* in culture. Induction therapy consisted of amphotericin B and fluconazole, adjusted based on therapeutic availability. Regarding clinical outcomes, one patient achieved neurological recovery. The second patient showed partial improvement during hospitalization but died at home three months later—during the consolidation phase—while receiving fluconazole treatment.

Conclusions: The late onset of central nervous system cryptococcosis in kidney transplant recipients underscores the need to maintain a high index of clinical suspicion beyond the period of peak immunosuppression. The coexistence of hyponatremia and neurological manifestations may indicate central nervous system cryptococcosis and should prompt early microbiological investigation to establish a diagnosis and initiate timely antifungal treatment.