TRANSLATIONAL PHYSIOLOGY Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

Axelsson J, Rippe A, Venturoli D, Swärd P, Rippe B. Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats. Am J Physiol Renal Physiol 296: F242–F248, 2009. First published November 12, 2008; doi:10.1152/ajprenal.90263.2008.—This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anesthetized Wistar rats, the left ureter was catheterized for urine collection while, simultaneously, blood access was achieved. Endotoxemia was induced by lipopolysaccharide (LPS) from Escherichia coli, and glomerular permeability was assessed at 60 and 90 (n 7) and 120 (n 7) min. Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min (n 8) and 40 min (n 9). Sham animals were followed for either 5 or 120 min. The glomerular sieving coefficients ( ) to fluorescein isothiocyanate-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). After start of the LPS infusion (2 h), but not at 60 or 90 min, for Ficoll70Å had increased markedly [from 2.91 10 5 6.33 10 6 to 7.78 10 5 6.21 10 6 (P 0.001)]. In anaphylaxis, there was a large increase in for Ficolls 60 Å in molecular radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases, to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter.