Effect of heparin on the glomerular structure and function of remnant nephrons

Abstract

The development of glomerular structural abnormalities in remnant nephrons, after ablation of renal mass (subtotal nephrectomy), in rats is largely prevented by the daily injection of heparin. To investigate if this protective effect of heparin is due to attenuation of glomerular hyperperfusion, hypertension and hyperfiltration, which develop in remnant nephrons soon after subtotal nephrectomy, we measured various parameters of glomerular hemodynamics at two weeks (Group 1) and four weeks (Group 2) after removal of 1-3/4 of total kidney mass in heparin-treated (Groups 1A and 2A) and untreated (Groups 1B and 2B) Munich-Wistar rats. When compared to normal non-nephrectomized rats (Group 1C), the values for glomerular capillary hydraulic pressure (P(GC)), glomerular plasma flow rate (Q(A)) and single nephron filtration rate (SNGFR) in remnant nephrons were found to be markedly and similarly elevated in both Groups 1A and 1B, averaging 71 ± 4 and 73 ± 4 mm Hg, 229 ± 41 and 176 ± 13 nl/min, 58.9 ± 6.4 and 60.8 ± 7.8 nl/min, respectively. Thus, glomerular hemodynamic parameters two weeks after subtotal nephrectomy did not differ between untreated and heparin-treated rats. Likewise, heparin treatment did not decrease the values of P(GC) and SNGFR assessed four weeks after subtotal nephrectomy, with the average values being 65 ± 2 mm Hg and 83.8 ± 7.1 nl/min in Group 2A versus 62 ± 4 mm Hg and 63.7 ± 6.5 nl/min in Group 2B. Thin-section light microscopic studies revealed that most of the remnant glomeruli of heparin-treated rats remained structurally intact throughout the entire study period of 7.5 weeks. In non-treated rats progressive destruction of glomerular architecture developed and normal glomeruli comprised 23 ± 7% of the total remaining nephron population at 7.5 weeks after subtotal nephrectomy. Therefore, the effect of heparin in protecting glomeruli of remnant nephrons from structural damage is mediated by a mechanism independent of glomerular hyperperfusion, hypertension or hyperfiltration occurring in these nephrons. The importance of an anticoagulant and/or antiproliferative effect of heparin is suggested as playing a role in the protection of glomerular structure.