Abstract

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

Highlights

  • Leptospirosis, caused by Leptospira spp infection, is one of the most common anthropozoonoses in the world [1]

  • A great number of possible virulent factors such as hemolysin, flagellin, heat shock protein, outer membrane proteins (OMPs), lipopolysaccharides (LPS), glycolipoproteins (GLP) and others have been thought to be accountable for the infection, but to date, their effective role in leptospirosis pathogenesis is still unclear

  • The renal injury observed in leptospirosis frequently produces a polyuric form of acute renal injury, followed by hypokalemia with an elevated urinary fractional excretion of potassium and an inability to concentrate urine

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Summary

Introduction

Leptospirosis, caused by Leptospira spp infection, is one of the most common anthropozoonoses in the world [1]. The renal injury observed in leptospirosis frequently produces a polyuric form of acute renal injury, followed by hypokalemia with an elevated urinary fractional excretion of potassium and an inability to concentrate urine. This increased kaliuresis is due to a decrease of potassium reabsorption in the damaged proximal tubule and to an increase of its secretion in the distal tubules [4,5,6,]. The concentrating defect is due, at least in part, to a decrease in the water permeability in the inner medullary collecting duct (IMCD) probably produced by a bacterial endotoxin [7]. 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)

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