title: Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation.
abstract: 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.
authors.affiliation: Department of Pathology, S. Paulo University Medical School, Av. Dr. Enéas de Carvalho Aguiar 470, São Paulo, Brazil.
authors.forename: Eduardo Rocha
authors.initials: ER
authors.lastname: Araujo
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
authors.forename: Anne
authors.initials: A
authors.lastname: Spichler
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Magaldi
authors.forename: Rildo A
authors.initials: RA
authors.lastname: Volpini
authors.forename: Thales
authors.initials: T
authors.lastname: De Brito
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051398:Aquaporin 1 / Q000378:metabolism; D051399:Aquaporin 2 / Q000378:metabolism; D001344:Autopsy; D005260:Female; D006801:Humans; D007668:Kidney / Q000382:microbiology* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007919:Leptospira / Q000302:isolation & purification; D007922:Leptospirosis / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1
chemical_list: C496020:AQP1 protein, human; C496023:AQP2 protein, human; D051399:Aquaporin 2; C578714:SLC12A1 protein, human; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D051398:Aquaporin 1; D000254:Sodium-Potassium-Exchanging ATPase