Abstract The morphological basis of diabetic nephropathy has been studied using light and electron microscopy. Kidneys of streptozotocin-induced diabetic rats were examined on the light microscope at 4 weeks and 8 months after induction of diabetes mellitus. In addition, the 8-month diabetic kidneys were examined with the electron microscope. Renal hypertrophy was evidenced by the increase in the weight of kidneys of diabetic rats. Whilst the diabetic kidneys were approximately twice as large after 4 weeks they were only 30% larger compared to age-matched controls after 8 months of induction of diabetes. After 4 weeks, light microscopy revealed dilated tubules within the cortex of the diabetic kidneys. Light microscopy showed a significant amount of destruction of the distal convoluted tubules while electron microscopy revealed a spectrum of damage that included basement membrane thickening, loss of podocytic foot processes, disruption of tubular basal infoldings and their related mitochondria and fibrosis of the tubules 8 months after induction of diabetes. It is concluded that renal hypertrophy persists after a pro- longed occurrence of diabetes but the extensive damage and loss of renal tissue including the loss of the foot processes of podocytes might be partly responsible for the clinical pre- sentation of diabetic nephropathy. Keywords: Diabetes, glomerulus, morphology, nephropathy, rat kidney, streptozotocin. Introduction The kidney has become an important organ for the investi- gation of the pathophysiology of diabetes mellitus and its complications and several animal experiments have been conducted to reproduce the typical human diabetic lesions of nephromegaly, mesangial expansion and basement mem- brane thickening. Of these animal models, the streptozotocin (STZ) rat model has been most extensively studied to eluci- date the morphological, physiological and biochemical changes in the diabetic kidney. In the STZ rat model, functional and structural features of nephropathy appear within 6 months (Hirose et al., 1982) but indications of renal disease such as an increase in glomeru- lar filtration rate [GFR], renal plasma flow and renal hyper- trophy develop within a week of induction of the disease (Seyer-Hansen, 1983, 1987; Allen et al., 1990; Bach and Jerums, 1990). The underlying mechanisms of the increase in GFR (hyperfiltration), however, still remain unknown inspite of intense research in this field. The association between renal hypertrophy and hyperfiltration has also been described in man (Mogensen & Andersen, 1973). It has been shown that there is a progressive rise in rat urinary albumin excretion (Cooper et al., 1988) analogous to the phases of albuminuria (microalbuminaemia to macroalbuminaemia) seen in man (Mogensen et al., 1983) and that while protein- uria is evident in most diabetic animals, it is not as abundant as in humans. It has been suggested that this major sieving defect may be due to the loss of selective macromolecular size permeability by the glomerular capillary (Michels et al., 1982), possibly related to diminished heparan sulfate syn- thesis (Rohrbach, 1986) resulting in reduced glomerular basement membrane (GBM) barrier density and ionic charge (Van den Born et al., 1995). Ultrastructural changes observed in both diabetic animals and humans include thickening of GBM and mesangial expansion (Steffes & Mauer, 1984; Cooper et al., 1988). Several studies have also shown that the synthesis of various mesangial and glomerular components is considerably enhanced in diabetes (Fukui et al., 1993; Accepted: 6 September, 2001 Address correspondence to: Prof. A. Adem, Dept. of Pharmacology, Faculty of Medicine and Health Sciences, P.O. Box 17666, Al Ain, United Arab Emirates University, Tel.: 971-3-7039522; Fax: 971-3-7672033; E-mail: abdu.adem@uaeu.ac.ae Morphological Changes in the Rat Kidney Following Long-Term Diabetes E.N. Obineche 1 , E. Mensah-Brown 2 , S.I. Chandranath 3 , I. Ahmed 2 , O. Naseer 3 and A. Adem 3 Departments of Internal Medicine 1 Anatomy 2 and Pharmacology 3 , Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates Archives of Physiology and Biochemistry 1381-3455/01/10903-241$16.00 2001, Vol. 109, No. 3, pp. 241–245 © Swets & Zeitlinger Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by United Arab Emirates University on 11/27/14 For personal use only.