Caracterização clínica e genotípica da Criptococose em pacientes submetidos a transplante renal

• Ano de defesa: 2019
• Autor(a) principal: Silva, Vinicius Ponzio Da [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Criptococose; Transplante De Rim; Cryptococcus; Técnicas De Genotipagem
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7590759; https://repositorio.unifesp.br/handle/11600/59211

Cryptococcosis is the second most common invasive fungal infections in renal transplant recipients and Brazil has substantial genotypic diversity in C. neoformans/C. gattii species complexes. Clinical outcome of cryptococcosis, graft outcome after treatment and the impact of the molecular type of the yeasts in renal transplant recipients have been scarcely studied, especially in less resource-available countries. Article 1: The purpose of this study was to assess renal allograft dysfunction and its impact on renal transplant recipients with cryptococcosis receiving antifungal therapy. Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss and mortality rates were evaluated. Predictors of mortality and graft loss were estimated. A total of 38 (97.4%) patients treated with amphotericin B deoxycholate showed graft dysfunction and eight (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels and graft dysfunction concomitant to amphotericin B deoxycholate therapy and an additional renal injury condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high cerebrospinal fluid opening pressure, positive cerebrospinal fluid India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with amphotericin B deoxycholate and an additional renal injury condition and graft loss within 30 days. The rate of graft loss rate was high, most frequently in patients with concomitant renal injury conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population. Article 2:The purpose of this study was to characterize the molecular types of C. neoformans/C. gattii species complexes and assess the factors associated with clinical outcome of cryptococcosis in renal transplant recipients in Brazil. We examined the genotypic diversity and fluconazole susceptibility pattern of 82 C. neoformans and C. gattii isolates from 60 renal transplant recipients. Clinical characteristics of the patients and prognostic factors were analyzed. A total of 72 (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = 0.012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3% and it was significantly associated with fungemia and absence of headache. Furthermore, patients infected with VGII had a particularly high mortality rate at 90 days (66.7%). A variety of molecular types produces disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. Cryptococcosis in renal transplant recipients is associated with high mortality in less-available resource health care settings. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and certain clinical characteristics on the patient outcome in this high risk population.