Renal involvement in leptospirosis: new insights into pathophysiology and treatment

Abstract

Acute renal failure (ARF) is one of the most common complications of leptospirosis although the causal mechanisms are still unclear. Diverse mechanisms are implicated in leptospiral nephropathy and new data supports the role of peculiar ion transport defects. Besides antibiotic therapy, ARF management in leptospirosis requires dialytic therapy which is most efficient when started early. Dialysis is the standard supportive therapy even though recent evidence suggests clinical benefit from alternative treatments such as plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical improvement. The comprehension of the primary mechanisms of renal dysfunction will be helpful in the development of additional therapeutic tools for improving supportive therapy for leptospiral nephropathy. This review discusses new insights into mechanisms implicated in leptospiral ARF and recent advances in treatment.

Insuficiência renal aguda associada à leptospirose

“…12 In some countries, such as Thailand and Singapore, leptospirosis accounts for more than 20% of the cases of AKI. 13 In the state of São Paulo, Brazil, 7,374 cases were notified in the past ten years, corresponding to 22 …”

“…21 physiopathology Renal impairment is a frequent complication in patients with the severe form of leptospirosis, mainly characterized by an association of interstitial and tubular damage. 22 The major factors involved in the pathogenesis of AKI in leptospirosis are the direct nephrotoxic action of the leptospira and the toxin-induced immune response. Hemodynamic alteration, jaundice, and rhabdomyolysis are also associated with the genesis of AKI in leptospirosis (Figure 1).…”

“…22 Some studies have suggested that AIN occurs after tubular damage. Patients who died within the first week of the disease had acute tubular necrosis (ATN) and cell edema, while those who died within two to three weeks of disease had ATN and interstitial edema, and those dying after three weeks had severe and diffuse interstitial nephritis.…”

“…Patients who died within the first week of the disease had acute tubular necrosis (ATN) and cell edema, while those who died within two to three weeks of disease had ATN and interstitial edema, and those dying after three weeks had severe and diffuse interstitial nephritis. 22 Both lesions are associated with the presence of leptospira antigens in the renal tissue. The presence of that bacterium in the mesangium and renal interstitium has already been observed in experimental studies, three to six hours after inoculation of L. icterohaemorrhagiae.…”

Attenuated Nephritis in Inducible Nitric Oxide Synthase Knockout C57BL/6 Mice and Pulmonary Hemorrhage in CB17 SCID and Recombination Activating Gene 1 Knockout C57BL/6 Mice Infected with Leptospira interrogans

“…We have also reported the association between high serum levels of nitric oxide (NO) and the severity of renal involvement in patients with severe leptospirosis (9) Renal production of NO could be involved in transport defects in renal tubular cells (4). In vitro studies have previously reported the activation of a broad range of inflammatory genes, such as those for transcription factor NF-B, inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1, and tumor necrosis factor alpha, by renal tubular cells in response to exposure to leptospire-derived products.…”