Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

Abstract

Antonio V Gaddi1, Arrigo FG Cicero1, Giovanni Gambaro21Atherosclerosis and Metabolic disease Research Unit, Internal Medicine, Aging and Kidney diseases Dept., University of Bologna, Italy; 2Nephrology and Dialysis Unit, Gemelli University Hospital, Sacred Heart Catholic University, Rome, ItalyAbstract: A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin–angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment.Keywords: glycosaminoglycans, sulodexide, albuminuria, proteinuria, diabetic nephropathy