Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France

Abstract

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.

Diagnosis and Treatment of Fungal Infections in Lung Transplant Recipients

“…In a multicenter study of cryptococcal infections, 54% were identified as having pulmonary infections, 52.2% had CNS involvement, and 8.1% had skin/soft tissue/osteoarticular infections [ 107 ]. In a study of kidney transplant patients, presenting symptoms in cases of cryptococcal meningitis were headache, focal neurological signs, fever, and vomiting [ 109 ]. Cryptococcal pneumonia typically radiographically presents as solitary or multiple nodules.…”

Pulmonary Cryptococcosis

“…In HIV/AIDS, infection typically manifests with CD4 T-lymphocyte counts under 100 cells/µL [26]. Other risk factors for cryptococcal disease include solid organ transplant [27], calcineurin inhibitors and other immunomodulatory agents [28], auto-antibodies against granulocyte-macrophage-colony stimulating factor (anti-GM-CSF) [29], decompensated cirrhosis [28], type 2 diabetes mellitus, malignant solid tumours, autoimmune diseases and chronic kidney disease [30]. Pulmonary disease in all these contexts is common although dissemination has been reported to be associated with pre-existing renal impairment [31].…”

Entrapment Syndrome in a Kidney Transplant Recipient with Cryptococcal Meningitis

“…As an opportunistic pathogen, C. neoformans primarily affects those who are immunocompromised due to conditions such as acquired immunodeficiency syndrome, organ transplantation on immunosuppressive agents, or malignancy on anti-cancer drugs [ 1 , 3 ]. Specifically, among solid organ transplant recipients who contracted invasive fungal infections, cryptococcal infection occurred in approximately 8% of the patients, with most cases occurring after 12 months following transplantation [ 4 , 5 ].…”

“…The central nervous system (CNS) is the most common site of disseminated infection; however, the skin and soft tissue, eyes, bones, prostate, and lymph nodes may all be involved as well. In kidney transplant patients with cryptococcal meningitis, diagnostic delays occur due to non-specific symptoms, and the mortality rate can be as high as 40% at 12 months [ 5 , 6 ].…”