Diabetic glomerulopathy in the uninephrectomized rat resists amelioration following islet transplantation

Uninephrectomy is known to accelerate the development of both functional and morphological changes seen with experimental diabetic nephropathy in the rat. The present experiments utilized electron and light microscopic morphometric techniques to assess glomerular basement membrane width and the volumes of the total mesangium and its cellular and matrix components of inbred Lewis rats made diabetic at 6 weeks of age and uninephrectomized 9 days later. Immunofluorescent microscopy was used to evaluate IgG and C₃ in the mesangium. The reversibility of established diabetic glomerular lesions in uninephrectomized diabetic rats after 7 months of diabetes was studied by performing intraportal transplant of neonatal pancreatic tissue. Renal biopsies were taken 2 months later in transplanted and non-transplanted animals. Islet transplantation lowered plasma glucose to normal levels (29.6 to 7.3 mmol/l) and raised plasma insulin values (6.3 to 53 μU/l). Glomerular basement membrane width in transplanted rats (268 nm) still exceeded the same measure (226 nm) in nondiabetic uninephrectomized rats. In transplanted animals volumes of the mesangium (0.51 × 10⁶ μm³) and of its cellular (0.27 × 10⁶ μm³) and matrix (0.24 × 10⁶ μm³) components remained higher than similar measures in control rats (0.32 × 10⁶, 0.17 × 10⁶ and 0.15 × 10⁶ μm³, respectively). Mesangial IgG in treated animals approached normal, but mesangial C₃ remained similar to levels in non-transplanted diabetic control animals. These observations in uninephrectomized-diabetic rats contrast with previous observations in intact diabetic rats in which mesangial volumes and localization of immunoglobulins and complement returned to normal levels following islet transplantation.