Aldose reductase and the development of renal disease in diabetic dogs

Effects of 5 years administration of an aldose reductase inhibitor (Sorbini l) on renal structure and albumin excretion were evaluated in diabetic dogs . Glycemia, estimated by frequent measurements of HbA(1), glycated plasma p roteins and glucosuria, was kept comparable between the placebo- and Sorbin il-treated diabetic groups. Kidney structure was evaluated using morphometr ic techniques by light and electron microscopy, and excretion of immunoreac tive albumin was measured yearly. Placebo-treated diabetic dogs developed n ephromegaly, glomerular enlargement, increased mesangial volume, and baseme nt membrane thickening during the 5 years of study, and by the fifth year, excreted greater than normal quantities of albumin. Sorbinil treatment prev ented sorbitol accumulation in erythrocytes and tended to have a similar ef fect in renal cortex, but had no beneficial effect on renal structure or al buminuria, Experimental galactosemia, another model of polyol over-producti on, failed to produce nephromegaly, glomerular enlargement, or mesangial ex pansion in dogs even after 5 years of galactose-feeding. The results sugges t that polyol over-production and/or accumulation per se are not sufficient to account for the nephromegaly, glomerular enlargement, or increased mesa ngial volume observed in diabetic dogs, (C) 1999 Elsevier Science Inc.