MORPHOMETRIC DETECTION OF INCIPIENT GLOMERULAR-LESIONS IN DIABETIC NEPHROPATHY IN RATS - PROTECTIVE EFFECTS OF ACE-INHIBITION

BACKGROUND: Glomerulosclerosis is the main renal lesion complicating d iabetes in humans and in experimental models. Angiotensin I converting enzyme (ACE) inhibitors are effective in preventing the development o f diabetic nephropathy. Incipient glomerular lesions were explored in streptozotocin-diabetic rats at a stage when glomerulosclerosis was no t yet established. The modulation of such early glomerular lesions by a new ACE inhibitor (Trandolapril (T)) at high or low doses was assess ed. EXPERIMENTAL DESIGN: Five groups of rats were designed as follows: (a) nondiabetic control rats, (b) diabetic rats, (c) diabetic rats tr eated with 0.1 mg/kg/day of T, (d) diabetic rats treated with 1 mg/kg/ day of T, and (e) nondiabetic rats treated with 1 mg/kg/day of T. The rats were killed at 1, 3, and 6 months after the beginning of the trea tment. The kidneys were studied using a powerful morphometric techniqu e at optical microscopic level with an image analyzer to measure the f ollowing glomerular parameters to assess the development of incipient glomerular lesions: (a) total glomerular surface area, (b) glomerular tuft surface area, (c) mesangial surface area, (d) ratio of the mesang ial surface area to the glomerular tuft surface area, and (e) mean thi ckness of the Bowman's capsule. In parallel, albuminuria was measured. RESULTS: The results showed the development of glomerular hypertrophy in parallel with the increase in glomerular mesangial domain and in a lbuminuria with diabetes. They also demonstrated that ACE inhibitor gi ven at a high dose is significantly effective in reducing glomerular h ypertrophy and the expansion of the mesangial domain. ACE inhibitor gi ven at a low dose tended to reduce glomerular hypertrophy and the expa nsion of the mesangial domain. Furthermore, ACE inhibitor at both dose s completely abolished the albuminuria increase, maintaining the level s of albuminuria within the range of young nondiabetic rats. CONCLUSIO NS: Using morphometric image analysis, incipient glomerular changes ca n be detected before glomerulosclerosis is patent in experimental diab etes. Moreover, they can be easily and reliably quantified by this tec hnique, allowing comparison among experimental groups. These changes c an be prevented by ACE inhibition.