Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis
Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis
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DOI：
10.2215/cjn.00590120
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发表时间：
2020-07-01
影响因子：
9.8
通讯作者：
Audard, Vincent
中科院分区：
文献类型：
--
作者：
Amoura, Ariane;Moktefi, Anissa;Audard, Vincent
背景和目标疟疾是一种可能危及生命的疾病，是全世界最流行的地方性传染病。在现代，对疟疾感染后患者中观察到的肾小球受累范围的描述仍然很少。因此，设计、设置、参与者和测量我们进行了一项回顾性多中心研究，以评估法国急性疟疾发作 3 个月内肾活检证实的肾小球疾病患者的临床、生物学、病理和治疗特征。结果我们确定了 23 名患者（12 名男性），除 1 名外均具有非洲血统，其中包括 10 名患有合并症的患者艾滋病毒感染。所有输入病例均为居住在法国的法国公民，他们最近从流行地区返回法国，并在返回法国后患上疟疾。十一名患者就诊时必须被送入重症监护室。 22名患者检出恶性疟原虫，1名患者检出三日疟原虫。成功治疗疟疾后（平均初次发病后 24 天）进行了肾活检。此时，所有患者均出现 AKI，其中 12 名患者需要 KRT。 17 名患者被诊断为肾病综合征。病理结果包括 21 名患者出现 FSGS，2 名患者出现微小病变肾病综合征。在 FSGS 患者中，18 例患有塌陷性肾小球病（其中 9 例患有 HIV 相关肾病）。在四名患者中，使用针对恶性疟原虫富含组氨酸的蛋白 2 的抗体进行的免疫组织化学显示，肾小管细胞中存在疟疾抗原，但足细胞或壁上皮细胞中不存在疟疾抗原。对 apoL1 风险基因型的分析表明，所有 7 名接受测试的患者都存在高风险变异。平均随访 23 个月后，8 名患者需要 KRT（其中 2 名患者进行肾移植），其他患者的平均 eGFR 为 51 ml/min 每 1.73 m(2)。结论在非洲血统患者中，输入性疟原虫感染可能是继发性 FSGS 的新致病因素，特别是 APOL1 高危变异背景下的塌陷性肾小球病变异。
Background and objectivesMalaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described.Design, setting, participants, & measurementsWe therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode.ResultsWe identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m(2).ConclusionsIn patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background.