RESUMO
Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor that has been widely used for the treatment of patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. However, in the HBV monoinfection scenario, only five cases of TDF-associated Fanconi syndrome have been reported thus far, two of them providing a confirmatory kidney biopsy. Here, we describe the case of a 68-year-old woman with chronic hepatitis B (CHB) who developed TDF-induced Fanconi syndrome that reverted after TDF withdrawal from tenofovir alafenamide. Though the overall risk of TDF-associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular functions should be monitored in patients exposed to TDF.
Assuntos
ADP-Ribosil Ciclase 1/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leishmaniose Visceral/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Infecções Oportunistas/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/antagonistas & inibidores , ADP-Ribosil Ciclase 1/imunologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antiprotozoários/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Masculino , Glicoproteínas de Membrana/imunologia , Mieloma Múltiplo/imunologia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/parasitologia , Recidiva , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologiaRESUMO
OBJECTIVE: To estimate the prevalence and investigate the clinical features and the outcome of clinically significant renal involvement in a large cohort of patients with primary Sjögren's syndrome (SS). METHODS: Among 715 patients who met the American-European Consensus Group criteria for primary SS, those with clinically significant renal involvement were identified and their clinical and immunologic features were recorded. The prognosis in patients with primary SS with renal involvement was assessed by the clinical appearance of any of the following major outcomes: death, hemodialysis, chronic renal failure (CRF), and lymphoma. Kaplan-Meier analysis was applied to compare death rates between patients without and those with renal involvement. RESULTS: Thirty-five patients with primary SS (4.9%) had clinically significant renal involvement, representing a total followup time after renal diagnosis of 252.2 person-years. Thirteen patients (37.1%) had interstitial nephritis alone, 17 patients (48.6%) had glomerulonephritis (GN) alone, and 5 patients (14.3%) had both entities. Nine patients died (25.7%), 11 developed CRF (including 4 requiring chronic hemodialysis) (31.4%), and 9 developed lymphoma (25.7%). The overall 5-year survival rate was 85%. Kaplan-Meier analysis showed statistically significant reduced survival for patients with primary SS with renal involvement compared to those without renal involvement (P < 0.0001 by log rank test), with GN patients displaying increased mortality. Eight of 9 reported deaths (89%) and 8 of 9 lymphomas (89%) were observed among patients with GN. CONCLUSION: The long-term prognosis varies for patients with primary SS who have clinically significant renal involvement. Patients with interstitial nephritis display a favorable prognosis, while patients with GN are at high risk of developing lymphoma and have poor survival.
Assuntos
Glomerulonefrite/mortalidade , Nefrite Intersticial/mortalidade , Insuficiência Renal Crônica/mortalidade , Síndrome de Sjogren/mortalidade , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Nefrite Intersticial/patologia , Nefrite Intersticial/terapia , Prognóstico , Diálise Renal , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapia , Fatores de Risco , Acidente Vascular Cerebral/mortalidadeRESUMO
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease mostly affecting the exocrine glands. A large number of autoantibodies have been detected in the serum of patients with pSS. Among them, anti-Ro/SSA and anti-La/SSB autoantibodies are the most common; they serve as disease markers and are involved in the pathogenesis of neonatal lupus syndrome (NLS). Other autoantibodies are associated with significant clinical phenotypes, such as cryoglobulins with development of non-Hodgkin's lymphoma, anti-centromere antibodies with Raynaud's phenomenon and anti-mitochondrial antibodies with liver pathology. As a result, pSS patients can be schematically categorized in subgroups according to their serological profile. Although the clinical utility of these autoantibodies is appreciated, little is known about the mechanisms related to their production and the regulation of the autoimmune response. In the present review, the clinical subsets of patients with pSS related to different autoantibodies as well as the regulating mechanisms of their production with special emphasis on idiotypic/anti-idiotypic network are discussed.