Pathophysiology of Leptospirosis

Seguro, Antonio Carlos*; Andrade, Lúcia*†

doi: 10.1097/SHK.0b013e31828fae49
Original Article

ABSTRACT: Leptospirosis is an acute septicemic illness that affects humans in all parts of the world. Approximately 10% of patients with leptospirosis develop severe disease, the Weil syndrome, with jaundice, acute kidney injury (AKI), and pulmonary hemorrhage. Leptospirosis-induced AKI is typically nonoliguric with a high frequency of hypokalemia. Experimental and clinical studies demonstrated that tubular function alterations precede a drop in the glomerular filtration rate and are mainly in the proximal tubule. Studies in humans and animals have demonstrated a decrease in the expression of proximal sodium (NHE3) and water tubular transporter, aquaporin 1 (AQP1) together with higher renal expression of the Na-K-2Cl cotransporter NKCC2. In an experimental model, at the initial phase of the disease, the expression of AQP2, the water transport of the collecting duct, is decreased, which explains the higher incidence of nonoliguric AKI. During the recovery phase of AKI, AQP2 expression increased in human and animals as a compensatory mechanism. Alveolar hemorrhage, pulmonary edema, acute respiratory distress syndrome, or a combination of these features may accompany AKI and is associated with high mortality. Studies with hamsters demonstrated that in leptospirosis a noncardiogenic pulmonary edema occurs consequently to a decrease in the clearance of alveolar fluid, due to a decrease in sodium transporter in the luminal membrane (ENaC) and an increase in the NKCC1 basolateral membrane transporter. Antibiotic treatment is efficient in the early and late/severe phases and revert all kidney transporters. Early and daily hemodialysis, low daily net fluid intake, and lung-protective strategies are recommended for critically ill patients with leptospirosis.

Author Information

*Laboratório de Investigação Médica (LIM-12) Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo; and Instituto de Infectologia Emílio Ribas, São Paulo, Brazil

Address reprint requests to Antonio Carlos Seguro, MD, PhD, Laboratório de Pesquisa Básica LIM-12, Faculdade de Medicina da USP, Av. Dr. Arnaldo 455, sala 3310, CEP 01246-903, São Paulo, Brazil. E-mail:

A.C.S. and L.A. are recipients of grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development; grants 309947/2009-0 and 302835/2009-1, respectively).

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