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

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 mu m/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 mu g/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 mu g) did not alter Vp action. In Group III, GLPc (250 mg) 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.