Glycosaminoglycan treatment in glomerulonephritis? An interesting option to investigate.
Patients with primary and secondary chronic glomerular diseases are at significant risk for progression to end-stage renal disease. Unfortunately the treatment armamentarium is relatively limited in terms both of available agents and of specificity. Experimental evidence supports the idea that heparin-derived agents and glycosaminoglycans (GAGs) favorably affect primary and secondary renal diseases. While a number of clinical exploratory studies have addressed the effect of these agents in microalbuminuric and macroalbuminuric diabetic patients, very few have investigated their activity in nondiabetic renal conditions. This paper will review the experimental and clinical evidence on the use of GAGs in renal disease other than diabetic nephropathy, following the reports of experimental findings supporting their use and the possible mechanisms involved: anticoagulant and antiproliferative activity, effect on growth factors (PDGF, FGF2 and TGF-beta1), inhibition of heparanase, macrophage renal infiltration and of the renin-angiotensin system, and decrease in proteinuria. Targeting these pathogenic loops with GAG treatment might be revealed to be very rewarding from a clinical point of view. Prospective randomized controlled trials with large case populations and definite entry criteria are clearly indicated.
Division of Nephrology and Dialysis, Columbus-Gemelli University Hospital, Renal Program, Catholic University, Rome - Italy. giovanni.gambaro@rm.unicatt.it
Giovanni
G
Gambaro
Norella C T
NC
Kong
D000925:Anticoagulants / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D005921:Glomerulonephritis / Q000188:drug therapy*; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D006025:Glycosaminoglycans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011507:Proteinuria / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics; D000099175:Heparanase
D000925:Anticoagulants; D005966:Glucuronidase; D006025:Glycosaminoglycans; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D000099175:Heparanase