Hyperglycemia and development of glomerular pathology: diabetes compared with galactosemia.

Dogs were randomly assigned to experimental galactosemia or diabetes, or to a normal untreated group, and diabetic animals were then randomly assigned to either poor or good glycemic control. At five years duration, kidneys from the animals were compared by quantitative stereology. Glomerulopathy appeared in the poor control diabetes group, and the thickness of glomerular capillary basement membrane, the glomerular tuft volume, and the fraction of glomerulus occupied by mesangium were each significantly greater than normal. The capillary filtering surface area per glomerulus was supranormal also, but nonetheless was subnormal relative to glomerular volume. The development of glomerulopathy was significantly inhibited in dogs assigned to good glycemic control. In galactosemic animals, the basement membrane thickness was greater than normal, but the glomerular volume, fractional and absolute volumes of mesangium, and capillary filtering surface area remained normal. The polyol concentration in renal cortex seemed elevated by galactosemia no less than by diabetes, and was highest in galactosemia. The galactosemic animals are known to have developed a retinopathy morphologically comparable to that of diabetic patients and diabetic dogs. Thus, sequelae of hyperglycemia sufficient to produce glomerular basement membrane thickening and retinopathy proved not necessarily sufficient to produce the mesangial expansion and glomerular hypertrophy typical of diabetes.