Araújo Stanley de Almeida, Cordeiro Thiago Macedo E, Belisário André Rolim, Araújo Roberto Ferreira de Almeida, Marinho Paula Eillanny Silva, Kroon Erna Geessien, de Oliveira Danilo Bretas, Teixeira Mauro Martins, Simões E Silva Ana Cristina
Instituto de Nefro Patologia, Belo Horizonte, Brazil.
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil.
Clin Kidney J. 2018 Nov 19;12(3):355-361. doi: 10.1093/ckj/sfy104. eCollection 2019 Jun.
The collapsing variant of focal segmental glomerulosclerosis (FSGS) is the most aggressive form of FSGS and is characterized by at least one glomerulus with segmental or global collapse and overlying podocyte hypertrophy and hyperplasia. Viruses can act as aetiological agents of secondary FSGS. This study aims to establish an aetiological link between dengue virus (DENV) infection and the collapsing variant of FSGS and to analyse possible influences of the gene risk alleles on the disease.
Biopsies and medical records were gathered from 700 patients of the Instituto de Nefropatologia, Belo Horizonte, Brazil. Screening for the collapsing variant of FSGS was performed and serological, immunohistochemical, tissue polymerase chain reaction (PCR) and genetic analysis were conducted.
Eight patients were identified with positive DENV serology and negative serological and/or tissue markers for hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human immunodeficiency virus, cytomegalovirus and parvovirus B19. In PCR analysis, six patients had positive markers for DENV strain genetic material, one patient had positive markers for co-infection of Zika virus (ZIKV) and DENV and one patient had positive markers only for ZIKV infection. Six of the eight patients did not show risk alleles of the gene. One patient had only one risk allele (G1) and the sample from another did not contain enough DNA for genetic analysis to be performed.
This study provided strong evidence that DENV can infect renal tissue and possibly functions as a second hit to the development of the collapsing variant of FSGS. Nonetheless, this study also highlights the possible implication of ZIKV infection in FSGS and supports the argument that risk alleles of the gene may not be implicated in the susceptibility to FSGS in these patients.
局灶节段性肾小球硬化(FSGS)的塌陷型是FSGS最具侵袭性的形式,其特征是至少有一个肾小球出现节段性或全球性塌陷,伴有足细胞肥大和增生。病毒可作为继发性FSGS的病因。本研究旨在建立登革病毒(DENV)感染与FSGS塌陷型之间的病因联系,并分析基因风险等位基因对该疾病的可能影响。
收集了巴西贝洛奥里藏特肾病研究所700例患者的活检标本和病历。对FSGS塌陷型进行筛查,并进行血清学、免疫组织化学、组织聚合酶链反应(PCR)和基因分析。
8例患者DENV血清学检测呈阳性,而乙肝病毒、丙肝病毒、EB病毒、人类免疫缺陷病毒、巨细胞病毒和细小病毒B19的血清学和/或组织标志物检测呈阴性。在PCR分析中,6例患者DENV毒株遗传物质标志物呈阳性,1例患者寨卡病毒(ZIKV)和DENV共感染标志物呈阳性,1例患者仅ZIKV感染标志物呈阳性。8例患者中有6例未显示该基因的风险等位基因。1例患者只有一个风险等位基因(G1),另1例患者的样本DNA含量不足,无法进行基因分析。
本研究提供了有力证据,证明DENV可感染肾组织,并可能作为FSGS塌陷型发展的二次打击因素。尽管如此,本研究也突出了ZIKV感染在FSGS中的可能影响,并支持了该基因的风险等位基因可能与这些患者FSGS易感性无关的观点。