Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

OCHOA FEDERICO; OLTRA GISELA; GERHARDT ELIZABETH; HERMES RICARDO; COHEN LILIAN; DAMIANO ALICIA; IBARRA CRISTINA; LAGO NESTOR; ZOTTA ELSA

International Journal of Nephrology and Renovascular Disease

Dovepress

Lugar: New York; Año: 2012 vol. 5 p. 29 - 36

1178-7058

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2–4% of patients die during the acute phase, and one third out of the 96% who survive are at risk of having chronic renal sequelae. Little information is available about the direct effectof Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. Here, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 g/kg body weight) to induce HUS. Functional, immunoblotting and immunohistochemistry studies werecarried out to determine alterations in slit diaphragm proteins and proximal tubule endocytic system at 48 h post-inoculation.We detected a significant increase in microalbuminuria, without changes in the proteinuria values respect to the control rats.Byimmunoperoxidase studies,the renal tubules and glomerularmesangium showed an increased expression oftransforming growth factor β1(TGF-β1). The expression of megalin was decreased by immunoperoxidase and cytoplasm showed a granular pattern of megalin expressionby immunofluorescence techniques.The western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins.We suggest that the alterations in slit diaphragm proteins and megalin expression could be related tothe development of microalbuminuria under lethal doses of Stx2.