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      Renal Involvement in Leptospirosis: The Effect of Glycolipoprotein on Renal Water Absorption

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          Abstract

          Background

          Leptospirotic renal lesions frequently produce a polyuric form of acute kidney injury with a urinary concentration defect. Our study investigated a possible effect of the glycolipoprotein, (GLPc) extracted from L. interrogans, on vasopressin (Vp) action in the guinea pig inner medullary collecting duct (IMCD).

          Methods

          The osmotic water permeability (Pf µm/s) was measured by the microperfusion in vitro technique. AQP2 protein abundance was determined by Western Blot. Three groups were established for study as follows: Group I, IMCD from normal (ngp, n = 5) and from leptospirotic guinea-pigs (lgp-infected with L. interrogans serovar Copenhageni, GLPc, n = 5); Group II, IMCD from normal guinea-pigs in the presence of GLPc (GLPc group, n = 54); Group III, IMCD from injected animals with GLPc ip (n = 8).

          Results

          In Group I, Pfs were: ngp- 61.8±22.1 and lgp- 8.8±12.4, p<0.01 and the urinary osmolalities were: lgp-735±64 mOsm/Kg and ngp- 1,632±120 mOsm/Kg. The lgp BUN was higher (176±36 mg%) than the ngp (56±9 mg%). In Group II, the Pf was measured under GLPc (250 µg/ml) applied directly to the bath solution of the microperfused normal guinea-pig IMCDs. GLPc blocked Vp (200 pg/ml,n = 5) action, did not block cAMP (10 −4 M,) and Forskolin (Fors- 10 −9 M) action, but partially blocked Cholera Toxin (ChT- 10 −9 M) action. GLP from L.biflexa serovar patoc (GLPp, non pathogenic, 250 µg) did not alter Vp action. In Group III, GLPc (250 µg) injected intraperitoneally produced a decrease of about 20% in IMCD Aquaporin 2 expression.

          Conclusion

          The IMCD Pf decrease caused by GLP is evidence, at least in part, towards explaining the urinary concentrating incapacity observed in infected guinea-pigs.

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          Most cited references36

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          Genome features of Leptospira interrogans serovar Copenhageni.

          We report novel features of the genome sequence of Leptospira interrogans serovar Copenhageni, a highly invasive spirochete. Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in mammals. Genomic sequence analysis reveals the presence of a competent transport system with 13 families of genes encoding for major transporters including a three-member component efflux system compatible with the long-term survival of this organism. The leptospiral genome contains a broad array of genes encoding regulatory system, signal transduction and methyl-accepting chemotaxis proteins, reflecting the organism's ability to respond to diverse environmental stimuli. The identification of a complete set of genes encoding the enzymes for the cobalamin biosynthetic pathway and the novel coding genes related to lipopolysaccharide biosynthesis should bring new light to the study of Leptospira physiology. Genes related to toxins, lipoproteins and several surface-exposed proteins may facilitate a better understanding of the Leptospira pathogenesis and may serve as potential candidates for vaccine.
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            Leptospirosis renal disease: understanding the initiation by Toll-like receptors.

            G. Yang (2007)
            Leptospirosis is a prevalent infectious disease affecting both humans and animals worldwide. This infection is associated with occupational or recreational exposure to animals as well as contact with leptospires, particularly in flood-prone areas. Multiple organ dysfunctions may be associated with acute severe leptospirosis. A triad presentation of fever, jaundice, and acute renal failure in patients with acute multiple organ dysfunction should alert physicians to possible leptospirosis. Penicillin is effective and can rescue multiple organ failure if administered early. Renal involvement is common in leptospirosis characterized by tubulo-interstitial nephritis, and tubular dysfunction. Leptospira outer membrane proteins (OMPs) may elicit tubular injury and inflammation through Toll-like receptors (TLRs)-dependent pathway followed by activation of nuclear transcription factor kappa B and mitogen-activated protein kinases and a differential induction of chemokines and cytokines relevant to tubular inflammation. Leptospira OMP may also induce activation of the transforming growth factor-beta/Smad-associated fibrosis pathway leading to accumulation of extracellular matrix. Thus, leptospirosis renal disease is a model for understanding the pathogenesis and initiation of pathogen-induced tubulo-interstitial nephritis and fibrosis. In particular, TLRs may be important mediators.
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              Acute Renal Failure of Leptospirosis: Nonoliguric and Hypokalemic Forms

              Acute renal failure induced by leptospirosis was studied in 56 patients. A higher frequency of nonoliguric renal failure was observed with lower morbidity and mortality rates than in oliguric forms. In addition, 45% of the patients in this series were hypokalemic, and no hyperkalemic patients were seen. A prospective study in 11 patients showed an initially elevated urinary fractional potassium excretion that fell simultaneously with the high urinary fractional sodium excretion and the urinary K/Na ratio, suggesting an increased distal potassium secretion due to an increased distal sodium delivery consequent to functional impairment of the proximal reabsorption of sodium.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                6 June 2012
                : 7
                : 6
                : e37625
                Affiliations
                [1 ]Basic Research Lab-LIM 12, Nephrology-HCFMUSP, São Paulo, São Paulo, Brazil
                [2 ]Bacteriology, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil
                [3 ]Bacteriology Laboratory, Instituto Butantan, São Paulo, São Paulo, Brazil
                Universidade de Sao Paulo, Brazil
                Author notes

                Conceived and designed the experiments: AJM. Performed the experiments: KRC ECR ACB RMB PAEA. Analyzed the data: AJM KRC. Contributed reagents/materials/analysis tools: AJM KRC ECR ACB RMB PAEA. Wrote the paper: AJM ECR PAEA.

                Article
                PONE-D-12-00191
                10.1371/journal.pone.0037625
                3368910
                22701573
                b3ad7326-a628-4795-b0be-31172b3e1dc5
                Cesar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 December 2011
                : 22 April 2012
                Page count
                Pages: 7
                Categories
                Research Article
                Medicine
                Anatomy and Physiology
                Fluid Physiology
                Renal System
                Critical Care and Emergency Medicine
                Acute Renal Failure
                Renal Critical Care
                Infectious Diseases
                Bacterial Diseases
                Leptospirosis
                Neglected Tropical Diseases
                Leptospirosis
                Nephrology
                Acute Renal Failure
                Veterinary Science
                Veterinary Diseases
                Zoonotic Diseases
                Leptospirosis

                Uncategorized
                Uncategorized

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