DIRECT PODOCYTE DAMAGE IN THE SINGLE NEPHRON LEADS TO ALBUMINURIA IN-VIVO

The hypothesis that detachment of podocytes leads to albuminuria was t ested by studying the single nephron albuminuria in vivo after injecti ng a saponin solution (0.6 mg/ml) in Bowman's space of superficial glo meruli, which produces selective damage of the podocytes, in female Mu nich-Wistar-Fromter rats. Animals were subsequently installed under a fluorescence microscope, a purified fluoresceinated rat albumin soluti on was intravenously injected and the passage of the fluorescent album in was followed through the microscope. Of the 47 glomeruli injected w ith the saponin solution (in 6 animals) 46 became fluorescent within s econds 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 de tected only in the glomerular tuft and the peritubular capillaries. Tu buli injected with the saponin solution remained indistinguishable fro m non-injected tubuli. Electron microscopic study of the saponin-injec ted glomeruli confirmed the selective removal of podocytes. Immunogold electron microscopy confirmed that the intact albumin molecule effect ively passed the glomerular capillary wall at the sire where podocyte detachment had occurred. It is concluded that selective removal of pod ocytes at the single nephron level leads to albuminuria in vivo, and t herefore podocytes play a crucial role in regulating the permeability of the glomerular capillary wall.