Direct podocyte damage in the single nephron leads to albuminuria in vivo

Abstract

The hypothesis that detachment of podocytes leads to albuminuria was tested by studying the single nephron albuminuria in vivo after injecting a saponin solution (0.6 mg/ml) in Bowman's space of superficial glomeruli, which produces selective damage of the podocytes, in female Munich-Wistar-Frömter rats. Animals were subsequently installed under a fluorescence microscope, a purified fluoresceinated rat albumin solution was intravenously injected and the passage of the fluorescent albumin was followed through the microscope. Of the 47 glomeruli injected with the saponin solution (in 6 animals) 46 became fluorescent within seconds with the fluorescence progressing from Bowman's space into the proximal tubule and then in the rest of the tubule. In superficial non-injected and control-injected glomeruli weak fluorescence could be detected only in the glomerular tuft and the peritubular capillaries. Tubuli injected with the saponin solution remained indistinguishable from non-injected tubuli. Electron microscopic study of the saponin-injected glomeruli confirmed the selective removal of podocytes. Immunogold electron microscopy confirmed that the intact albumin molecule effectively passed the glomerular capillary wall at the site where podocyte detachment had occurred. It is concluded that selective removal of podocytes at the single nephron level leads to albuminuria in vivo, and therefore podocytes play a crucial role in regulating the permeability of the glomerular capillary wall.