PODOCYTE LOSS AND PROGRESSIVE GLOMERULAR INJURY IN TYPE-II DIABETES

Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10) , microalbuminuria (n = 17), normoalbuminuria, despite a duration of d iabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhib ited moderate increases in glomerular and mesangial volume when compar ed with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of dia betes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in non-sclerosed glomeruli. Marked mesangial expansion was accompanied by a further in crease in total glomerular volume. Glomerular capillary surface area r emained stable, but the glomerular basement membrane thickness was inc reased and podocyte foot processes were broadened. Broadening of podoc yte foot processes was associated with a reduction in the number of po docytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contrib utes to the progression of diabetic nephropathy.