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Am J Physiol Renal Physiol 292: F586-F592, 2007. First published August 29, 2006; doi:10.1152/ajprenal.00102.2006
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Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

Lúcia Andrade, Adílson C. Rodrigues, Jr., Talita R. C. Sanches, Rodrigo B. Souza, and Antonio Carlos Seguro

Nephrology Department, Laboratory of Basic Science, University of São Paulo School of Medicine, São Paulo, Brazil

Submitted 28 March 2006 ; accepted in final form 23 August 2006

Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.

acute respiratory distress syndrome; acute renal failure



Address for reprint requests and other correspondence: A. C. Seguro, Laboratório de Pesquisa Básica LIM-12, Faculdade de Medicina da USP, Av. Dr. Arnaldo 455, Sala 3310, CEP 01246-903, São Paulo, SP, Brazil (e-mail: trulu{at}usp.br)




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