The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis

Abstract

Aims/hypothesis: We tested the hypothesis that diabetic glomerulosclerosis would develop more rapidly in animals with fewer glomeruli. Methods: We studied the female offspring of Wistar rats that had been fed a low-protein diet (LPD) containing 6% protein or a normal-protein diet (NPD) containing 18% protein during pregnancy. Streptozotocin diabetes was induced at 12 weeks and animals were killed at 40 weeks. Results: Non-diabetic LPD offspring were of lower birthweight than the NPD offspring (5.19± 0.64 vs 6.45±0.67 g, p<0.001) and had fewer glomeruli (27,402±3,137 vs 34,203±6,471, p<0.05). Glomerular volume correlated inversely with glomerular number (r=-0.64, p=0.035), but total glomerular filtration surface area was reduced in the LPD animals (4,770±541 vs 5,779±1,302 mm2, p=0.05). Other renal structural and functional parameters were similar. In LPD and NPD diabetic animals, glomerular volume and basement membrane width were significantly increased compared to their respective controls. Podocyte density was lowest in the LPD diabetic animals (not significant), and the area covered by each podocyte was greater in the LPD diabetic group (2.40±0.693 × 10-3 mm2) than in the LPD control group (1.68±0.374 × 10-3 mm2, p<0.001) and in the NPD diabetic animals (1.71±0.291 × 10-3 mm 2, p<0.05). There was no difference in any other structural or functional parameter between the LPD and NPD diabetic animals. Conclusions/interpretation: A decrease in glomerular number was not deleterious to renal structure and function over 40 weeks in this animal model. Further work in models with progressive renal impairment and hypertension is necessary to clarify the impact of glomerular number on the development of renal disease. © Springer-Verlag 2005.