Department of Microbiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
PLoS Negl Trop Dis. 2021 Jun 18;15(6):e0009410. doi: 10.1371/journal.pntd.0009410. eCollection 2021 Jun.
Leptospirosis has been described as a biphasic disease consisting of hematogenous dissemination to major organs in the acute phase and asymptomatic renal colonization in the chronic phase. Several observational studies have suggested an association between leptospirosis and chronic kidney disease (CKD). We investigated the dynamics of leptospires and histopathological changes in the kidney to understand the relationship between them, and also investigated the extent of renal dysfunction in the acute and chronic phases of leptospirosis using a hamster model.
Hamsters (n = 68) were subcutaneously infected with 1 × 104 cells of the Leptospira interrogans serovar Manilae strain UP-MMC-SM. A total of 53 infected hamsters developed fatal acute leptospirosis, and the remaining 15 hamsters recovered from the acute phase, 13 of which showed Leptospira colonization in the kidneys in the chronic phase. Five asymptomatic hamsters also had renal colonization in the chronic phase. Immunofluorescence staining showed that leptospires were locally distributed in the renal interstitium in the early acute phase and then spread continuously into the surrounding interstitium. The kidneys of the surviving hamsters in the chronic phase showed patchy lesions of atrophic tubules, a finding of chronic tubulointerstitial nephritis, which were substantially consistent with the distribution of leptospires in the renal interstitium. The degree of atrophic tubules in kidney sections correlated statistically with the serum creatinine level in the chronic phase (rs = 0.78, p = 0.01).
Subcutaneous infection with pathogenic leptospires could cause acute death or chronic leptospirosis in hamsters after surviving the acute phase. We suggest that the renal distribution of leptospires during the acute phase probably affected the extent of tubular atrophy, leading to CKD.
钩端螺旋体病被描述为一种双相疾病，包括急性阶段的血源播散到主要器官和慢性阶段的无症状肾脏定植。几项观察性研究表明，钩端螺旋体病与慢性肾脏病（CKD）之间存在关联。我们研究了钩端螺旋体在肾脏中的动态变化和组织病理学改变，以了解它们之间的关系，并使用仓鼠模型研究了钩端螺旋体病在急性和慢性阶段肾功能不全的程度。
仓鼠（n = 68）经皮下感染 1 × 104 个问号钩端螺旋体血清型 Manilae 菌株 UP-MMC-SM。共有 53 只感染的仓鼠发展为致命性急性钩端螺旋体病，其余 15 只仓鼠从急性阶段恢复，其中 13 只在慢性阶段显示肾脏定植钩端螺旋体。5 只无症状仓鼠在慢性阶段也有肾脏定植。免疫荧光染色显示，钩端螺旋体在早期急性阶段局部分布在肾间质中，然后持续扩散到周围间质。慢性阶段存活仓鼠的肾脏显示出萎缩肾小管的斑片状病变，这是慢性肾小管间质性肾炎的表现，与肾间质中钩端螺旋体的分布基本一致。肾切片中萎缩肾小管的程度与慢性期血清肌酐水平呈统计学相关（rs = 0.78，p = 0.01）。
皮下感染致病性钩端螺旋体后，仓鼠可在存活过急性期后发生急性死亡或慢性钩端螺旋体病。我们认为，急性阶段肾内钩端螺旋体的分布可能影响肾小管萎缩的程度，导致 CKD。
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