The renal clearance of dextran sulfate decreases in puromycin aminonucleoside-induced glomerulosclerosis: A puzzle observation

Abstract

Background Puromycin aminonucleoside-induced nephrosis is characterized by increased renal excretion of plasma proteins. We employed this experimental model to study the urinary clearance of dextran sulfate. Methods The dextran sulfate eliminated by the urine was determined using a metachromatic assay. Polysaccharide fragments were analyzed by chromatographic and electrophoretic procedures. Disaccharide composition of the glomerular heparan sulfate was assessed using digestion with specific lyases. Results In normal rats dextran sulfate is partially degraded to lower molecular weight fragments and only then eliminated by the urine. Surprisingly, in puromycin aminonucleoside-induced glomerulosclerosis the molecular size of the fragments of dextran sulfate found in the urine is the same or even lower than in control animals in spite of the marked proteinuria. Furthermore, urinary excretion of dextran sulfate decreases in the experimentally induced nephrosis. This observation cannot be totally attributed to a reduced number of physiologically active nephrons since the glomerular filtration rate decreases ∼ 32% after puromycin aminonucleoside administration while the urinary excretion of 8 kDa-dextran sulfate decreases 3-fold. The glomerular heparan sulfate shows reduced sulfation when compared with normal animals. Possibly puromycin aminonucleoside decreases the activity of kidney endoglycosidases, which reduce the molecular size of the sulfated polysaccharide, leading to a decrease in its renal clearance. Reduced sulfation of the glomerular heparan sulfate in the puromycin aminonucleoside-induced nephrosis does not alter the size of the dextran sulfate eliminated by the kidney, as suggested for protein. Conclusions Each pathological process induces a particular modification in the kidney, which in turn can affect the renal selectivity to specific macromolecules in different ways.