N-desulfated/acetylated heparin ameliorates the progression of renal disease in rats with subtotal renal ablation.

Abstract

The effect of administration of N-desulfated/acetylated heparin, almost completely devoid of anticoagulant activity, on the progression of renal disease was examined in rats with 13/4 nephrectomy. Three groups of rats with 13/4 nephrectomy were studied. Group I (control, n = 11) received 0.15 ml of 0.15 M NaCl subcutaneously twice daily for 5 wk; group 2 (n = 11) received 0.15 ml twice daily of N-desulfated/acetylated heparin (5.4 mg/ml; less than 0.5 U/ml); group 3 (n = 9) received 0.15 ml twice daily of standard beef lung heparin (5.4 mg/ml; 977 U/ml). Clearances and renal histological studies were done at the end of 5 wk of heparin or saline administration. Rats given the heparin preparations had significantly higher inulin clearances (2.55 +/- 0.38 ml/min per body weight (BW) for group 2, or 2.60 +/- 0.24 ml/min per kg BW for group 3) than control rats (1.59 +/- 0.20 ml/min per kg BW). Histological analysis revealed a greater number of glomeruli with segmental or global sclerosis, hyalinosis, or fibrosis (36.6%) in control rats than in rats receiving N-desulfated/acetylated heparin (6.2%) or standard heparin (3.0%). Blood pressure averaged 169.4 +/- 6.2 mmHg in controls, 119.1 +/- 6.1 in rats of group 2, and 124.3 +/- 2.5 in rats of group 3. The values for blood pressure were significantly lower in the two groups receiving heparin than in controls. These studies indicate that a heparin preparation, almost completely devoid of anticoagulant properties, affords the same degree of protection against progression of renal disease as does standard heparin in rats with subtotal renal ablation. It is suggested that other biological properties of heparin may be responsible for the effects observed.