Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation
Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation
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DOI：
10.1007/s00428-010-0894-8
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发表时间：
2010-04-01
期刊：
影响因子：
3.5
通讯作者：
De Brito, Thales
中科院分区：
文献类型：
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作者：
Araujo, Eduardo Rocha;Seguro, Antonio Carlos;De Brito, Thales
肾小管间质性肾炎是钩端螺旋体病的常见临床病理表现。临床上，钩端螺旋体病经常发生非少尿性急性肾损伤（AKI）、低钾血症、钠和镁消耗。肾脏受累的确切机制仍不清楚。对人类钩端螺旋体病病例尸检过程中取出的肾脏以及有或没有急性肾小管证据的人类非钩端螺旋体病病例尸检过程中取出的肾脏进行免疫组织化学检测，以检测内源性钠/氢交换异构体 3 (NHE 3)、水通道蛋白 1 和 2、α-Na(+)K(+)ATPase 以及钠钾氯化物协同转运蛋白在其 NKCC2 亚型中的表达坏死（ATN）。近曲小管细胞中 NHE 3、水通道蛋白 1 和 α-Na(+)K(+)ATPase 表达减少。水通道蛋白 1 的表达沿着外髓质亨利环的下降细肢保留。 α-Na(+)K(+)ATpase 表达基本上保留在远端小管中，即 Henle 环的粗升支、致密斑和远端曲小管中。与非钩端螺旋体肾脏相比，集合管中水通道蛋白 2 的表达增强。 NKCC2 共转运同工型在 Henle 环的粗升肢中表达，并且基本上保留在钩端螺旋体肾中。近曲小管的原发性损伤被认为是钩端螺旋体病肾脏的标志。钠和水的运输尤其受到远端钾排泄增加、低钾血症和多尿的影响。髓质集合管中水通道蛋白 2 表达的增强可能是肾衰竭非少尿期保留水分的一种尝试。
Tubulointerstitial nephritis is a common clinicopathological finding in leptospirosis. Clinically, nonoliguric acute kidney injury (AKI), hypokalemia, sodium, and magnesium wasting frequently occur in leptospirosis. The exact mechanisms of renal involvement remain largely unclear. Immunohistochemistry to detect expression of the endogenous sodium/hydrogen exchanger isoform 3 (NHE 3), aquaporin 1 and 2, alpha-Na(+)K(+)ATPase, and sodium-potassium-chloride cotransporter in its NKCC2 isoform was performed on kidneys removed during autopsy of human leptospirosis cases and kidneys removed during autopsy of human non-leptospirosis cases with and without evidence of acute tubular necrosis (ATN). A decrease in NHE 3, aquaporin 1, and alpha-Na(+)K(+)ATPase expression occurred in proximal convoluted tubule cells. Expression of aquaporin 1 was preserved along the descending thin limb of the loop of Henle in the outer medulla. alpha-Na(+)K(+)ATpase expression was essentially preserved in the distal tubules, i.e., the thick ascending limb of the loop of Henle, macula densa, and distal convoluted tubule. Aquaporin 2 expression in the collecting tubules was enhanced compared to those of non-leptospirotic kidneys. NKCC2 cotransport isoform was expressed in the thick ascending limb of the loop of Henle and was essentially preserved in leptospirotic kidneys. Primary injury of the proximal convoluted tubules is regarded as the hallmark of the kidney in leptospirosis. Sodium and water transport are particularly affected with increased distal potassium excretion, hypokalemia, and polyuria. Enhanced expression of aquaporin 2 in medullary collecting tubules is probably an attempt to retain water during the nonoliguric phase of renal failure.