Effects of Oral Administration of Heparan Sulphate in the Rat Remnant Kidney Model

Abstract

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 ± 22 vs. 80 ± 54 mg/24 h , p < 0.01), lower urea plasma levels (75 ± 34 vs. 134 ± 105 mg/dl, p < 0.01) and higher creatinine clearance (66 ± 15 vs. 47 ± 21 ml/min · 10², p < 0.05) than control rats. Remnant kidney weight (2.3 ± 1.1 vs. 1.3 ± 0.2 g, p < 0.01) and heart weight (1.3 ± 0.2 vs. 1.1 ± 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 ± 19 vs. 115 ± 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.