Reversal of Renal Tubule Transporter Downregulation during Severe Leptospirosis with Antimicrobial Therapy

Anne Spichler Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Albert I. Ko Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Everton Fagonde Silva Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Thales De Brito Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Ana Maria Silva Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Daniel Athanazio Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Cleiton Silva Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Antonio Seguro Department of Nephrology, LIM 12, University of São Paulo School of Medicine, São Paulo, Brazil; Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Salvador, Brazilian Ministry of Health, Salvador, Brazil; Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York; Biotechnology Centre, Federal University of Pelotas, Pelotas, Brazil; Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Biointeraction, Federal University of Bahia, Health Sciences Institute, Salvador, Brazil

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Tubular dysfunction is a hallmark of severe leptospirosis. Antimicrobial therapy is thought to interfere on renal involvement. We evaluated the expression of a proximal tubule type-3 Na+/H+ exchanger (NHE3) and a thick ascending limb Na+-K+-2Cl cotransporter (NKCC2) in controls and treated hamsters. Animals infected by a serovar Copenhageni isolate, were treated or not with ampicillin (AMP) and/or N-acetylcysteine (NAC). Leptospiral antigen(s) and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen(s) in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. NAC effect was restricted to lowering TBARS. Early and late AMP treatment rescued tubular defects in severe leptospirosis disease, and there was no evidence of benefit from antioxidant therapy.

Author Notes

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