Protamine sulphate-induced proteinuria: the roles of glomerular injury and depletion of polyanion.

It has been claimed that intrarenal injection of polycations results in proteinuria due to neutralization of glomerular basement membrane polyanionic charge without any glomerular morphological changes. To study the effects of polycation infusion on the renal glomerulus, the left kidney of rats was directly injected with protamine sulphate through the renal artery. Urine was collected from each kidney before and after injection, and protein excretion rates were determined. Ninety minutes after completion of the injection both kidneys were perfusion-fixed and the morphology and colloidal iron staining of the kidneys were studied by light and electron microscopy. Intrarenal injection of 0.5, 1, and 2 mg of protamine sulphate produced minimal or mild proteinuria in the majority of animals. Higher doses (5 mg) commonly resulted in decreased protein excretion associated with oliguria. Colloidal iron staining of glomerular polyanionic sites was undiminished when compared with control kidneys. Injection of protamine sulphate resulted in capillary thrombosis and severe damage to both glomerular and tubular epithelium in 6 of 16 kidneys. In the remaining kidneys, milder focal changes were apparent. Although its mechanism of action is unclear, it is apparent that protamine sulphate, even in small doses, is toxic to the cellular components of the glomerulus and tubules, thus accounting for the range of changes observed in renal function.