Epithelial cell foot process width in intact and uninephrectomized diabetic and nondiabetic rats

We measured foot process widths of glomerular epithelial cells in the peripheral capillary and mesangial areas of control, diabetic, and uninephrectomized diabetic animals receiving islet transplants. Diabetic animals, known to have significant albuminuria reversable with islet transplantation, had normal peripheral and mesangial foot process widths after 7 and 9 months of diabetes. Uninephrectomized nondiabetic animals, having more albuminuria than diabetic rats, had normal peripheral foot processes at 7 and 9 months. In uninephrectomized nondiabetic animals, mesangial foot processes were wider than those in control rats at both times, statistically significant only at 9 months. Uninephrectomized diabetic animals, having the greatest increase in albuminuria, demonstrated increased width of both peripheral and mesangial foot processes at 7 and 9 months. With all animals considered, mesangial foot processes were wider than peripheral foot processes. In diabetic rats receiving islet transplants slight reductions in the widths of peripheral and mesangial foot processes occurred within 2 months of transplantation. In uninephrectomized diabetic animals receiving islet transplants the widths of both peripheral and mesangial foot processes matched those of uninephrectomized nondiabetic rats at 2 months after transplantation, a reduction similar to previous observations with urinary albumin excretion. We conclude that albuminuria may exist without changes in epithelial cell foot process width. With increasing proteinuria, increased widening of foot processes tends to occur. These changes may first be noted in the mesangial foot processes and are not precisely related to urinary albumin levels. Islet transplantation results in decreased albuminuria and decreased foot process width, indicating reversibility of these abnormalities. Complex structural-functional changes of foot process width and albuminuria exist in diabetic and uninephrectomized rats. The causal nature of these relationships remains unclear.