Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment.
Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment.
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DOI：
10.3389/fcimb.2022.915792
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发表时间：
2022
影响因子：
5.7
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中科院分区：
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疟疾仍然是一种重要的全球疾病，每年有2亿多例病例和60万人死亡。高达40%的严重疟疾患者可能出现疟疾相关急性肾损伤（MAKI），并与死亡率增加有关。疟疾AKI的组织病理学特征为急性肾小管损伤、间质性肾炎、局灶节段性肾小球硬化、塌陷性肾小球病和肾小球肾炎。我们观察到感染伯氏疟原虫NK65 （PbNK65）的C57BL/6小鼠在发生MAKI的同时发生疟疾相关急性呼吸窘迫综合征（MA-ARDS）。MAKI病理与蛋白尿、急性肾小管损伤和肾小球毛细血管丛塌陷相关，经抗疟药物治疗后迅速消退。重要的是，在该模型中没有检测到肾脏中的寄生虫隔离。此外，通过使用骨架结合蛋白-1 (SBP-1) KO PbNK65寄生虫，我们发现寄生虫在其他器官的隔离及其随后的高寄生虫负荷并不需要实验性MAKI的发展。在两个感染组中观察到相似的蛋白尿、组织病理学特征，以及肾脏中干扰素-γ、TNF-α、肾损伤分子-1 （KIM-1）和血红素加氧酶-1 （HO-1）表达的增加，尽管寄生虫负荷有显著差异。综上所述，我们介绍了一种与疟疾患者AKI具有重要相似性的疟疾实验性AKI模型。因此，该小鼠模型可能对进一步研究AKI在疟疾中的发病机制具有重要意义。
Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria.