Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis.
Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis.
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DOI：
10.1371/journal.pntd.0005615
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发表时间：
2017-05
影响因子：
3.8
通讯作者：
B Magaldi AJ
中科院分区：
文献类型：
--
作者：
Abreu PAE;Seguro AC;Canale D;Silva AMGD;Matos LDRB;Gotti TB;Monaris D;Jesus DA;Vasconcellos SA;de Brito T;B Magaldi AJ
钩端螺旋体病所致的急性肾损伤(AKI)多为非少尿型，伴有低血钾或正常血钾。在死亡患者中观察到较高的血钾水平，可能是由更严重的AKI、代谢紊乱或横纹肌溶解引起的。在这些患者中观察到肌酸磷酸激酶(CPK)水平和最大血肌酐水平之间的关系，这表明横纹肌溶解导致严重的AKI和高钾血症。LipL32和Lp25是钩端螺旋体致病株的保守蛋白，但其功能未知。本研究评估了这些蛋白对豚鼠肾功能的影响。Lp25是一种外膜蛋白，似乎与横纹肌溶解引起的高钾血症(如CPK、尿酸和血磷升高)相关的少尿酸型AKI的发生有关。这项研究首次描述了一种与钩端螺旋体病严重症状相关的钩端螺旋体外膜蛋白。减弱这种蛋白并抑制横纹肌溶解诱导的AKI的治疗方法可以保护动物和患者免受这种疾病的严重形式的影响，并降低死亡率。横纹肌溶解是一种由于骨骼肌完整性被破坏，导致细胞内物质大量释放到血流中的综合征，包括肌红蛋白、肌酸磷酸激酶、天冬氨酸转氨酶、乳酸脱氢酶、醛缩酶和电解质。横纹肌溶解症的并发症包括急性肾损伤(AKI)、高钾血症、高磷血症和低血容量血症，如不及早治疗可能导致死亡。这种综合征最常见的原因是创伤、肌肉过度活动、药物、毒素、电解质失衡、肌肉缺血、代谢紊乱和传染病。在钩端螺旋体病病例中，横纹肌溶解引起的AKI几乎仅见于严重形式的钩端螺旋体病患者。然而，横纹肌溶解在钩端螺旋体感染所致AKI发病机制中的作用尚不清楚。
Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo- or normokalemia. Higher serum potassium levels are observed in non-survivor patients and may have been caused by more severe AKI, metabolic disarrangement, or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level and maximum serum creatinine level has been observed in these patients, which suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32 and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but these proteins have no known function. This study evaluated the effect of these proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that appears responsible for the development of oliguric AKI associated with hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum phosphate). This study is the first characterization of a leptospiral outer membrane protein that is associated with severe manifestations of leptospirosis. Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced AKI could protect animals and patients from severe forms of this disease and decrease mortality. Rhabdomyolysis is a syndrome that results from the disruption of skeletal muscle integrity, leading to a massive release of the intracellular contents into the blood stream, including myoglobin, creatine phosphokinase, aspartate transaminase, lactate dehydrogenase, aldolase, and electrolytes. Complications of rhabdomyolysis include acute kidney injury (AKI), hyperkalemia, hyperphosphatemia, and hypovolemia, which may result in death without early treatment. The most frequent causes of this syndrome are trauma, excessive muscle activity, drugs, toxins, electrolyte imbalance, muscle ischemia, metabolic disorders, and infectious diseases. Among leptospirosis cases, the AKI induced by rhabdomyolysis has been described almost exclusively in patients with severe form of leptospirosis. However, the role of rhabdomyolysis in the pathogenesis of AKI due to leptospiral infection is not understood.