Effects of heparin on renal morphology and albuminuria in experimental diabetes

Female nondiabetic and streptozotocin diabetic Wistar rats received 200 units heparin two times daily by subcutaneous injection for 6 mo. Mesangial volume fraction was reduced in heparin-treated control (CH) compared with untreated control (C) animals (CH 0.18 +/- 0.02 vs. C 0.24 +/- 0.02, P < 0.05), but other histological parameters were similar. In the heparin-treated diabetic (DH) group, wet kidney weight was increased compared with the untreated diabetic (D) group (DH 1,156 +/- 39 vs. D 1,050 +/- 30 mg, P < 0.05), as were absolute, but not fractional, glomerular volume (P < 0.05) and capillary volume (P < 0.05). Basement membrane thickness (DH 193 +/- 3 vs. D 231 +/- 9 nm, P < 0.01) and mesangial/glomerular volume fraction (P < 0.001) were decreased. Urinary albumin excretion was increased in the heparin-treated control animals compared with control animals [CH 980 (range 150-4,446) vs. C 221 (range 86-654) mu g/24 h, P < 0.001] and in the heparin-treated diabetic animals compared with the diabetic animals [DH 12,785 (range 4,495-29,520) vs. D 899 (range 450-1,335) mu g/24 h, P < 0.001]. Thus the possibly deleterious increases in glomerular capillary volume and albumin excretion may negate the beneficial effects of heparin on mesangial and basement membrane structures.