Glomerular Charge and Urinary Protein Excretion: Effects of Systemic and Intrarenal Polycation Infusion in the Rat

To study the role of the fixed anionic sites of the glomerular capillary wall in protein filtration, the negative charges were neutralized in vivo. With systemic infusion of the polycation protamine sulfate, glomerular staining for polyanion was reduced and protein excretion increased by 154%. To avoid systemic side effects in subsequent studies, small doses of a polycation were infused directly into one renal artery. The contralateral kidney was infused with the vehicle solution. Albumin excretion from the experimental kidneys in the first 1-hr collection after infusing 0.5 mg protamine sulfate was 24.3 +/- 6.3 micrograms/min/kidney (N = 13; P less than 0.01). Albuminuria declined during the subsequent 3 hr with a second infusion inducing a second proteinuric response. The degree and longevity of the albuminuric response was correlated directly to the dose of protamine sulfate. The polycations hexadimethrine and poly-l-lysine also induced proteinuria. The increased protein excretion consisted of albumin; the excretion of nonalbumin protein was identical in the experimental and control kidneys. Hemodynamic factors did not explain the increase in proteinuria. Morphologically, the polycation-treated kidneys showed scanty foot process fusion and a decrease in free negative sites in the lamina rarae of the glomerular basement membrane. The results strongly support an important role for glomerular charge in preventing filtration of circulating plasma albumin.