Histopathology of Diabetic Nephropathy

Abstract

The clinical manifestations of diabetic nephropathy, proteinuria, increased blood pressure, and decreased glomerular filtration rate, are similar in type 1 and type 2 diabetes; however, the renal lesions underlying renal dysfunction in the 2 conditions may differ. Indeed, although tubular, interstitial, and arteriolar lesions are ultimately present in type 1 diabetes, as the disease progresses, the most important structural changes involve the glomerulus. In contrast, a substantial subset of type 2 diabetic patients, despite the presence of microalbuminuria or proteinuria, have normal glomerular structure with or without tubulointerstitial and/or arteriolar abnormalities. The clinical manifestations of diabetic nephropathy are strongly related with the structural changes, especially with the degree of mesangial expansion in both type 1 and type 2 diabetes. However, several other important structural changes are involved. Previous studies, using light and electron microscopic morphometric analysis, have described the renal structural changes and the structural-functional relationships of diabetic nephropathy. This review focuses on these topics, emphasizing the contribution of research kidney biopsy studies to the understanding of the pathogenesis of diabetic nephropathy and the identification of patients with a higher risk of progression to end-stage renal disease. Finally, evidence is presented that the reversal of established lesions of diabetic nephropathy is possible.

Diabetic Nephropathy Is Associated with Oxidative Stress and Decreased Renal Nitric Oxide Production

“…There is a significant heterogeneity in renal lesions of nephropathy in type 2 diabetes, unlike in type 1 diabetes. 4 Although DN was traditionally considered a primarily glomerular disease, it is now widely accepted that the rate of deterioration of function correlates best with the degree of renal tubulointerstitial fibrosis. 5 A substantial subset of patients with type 2 diabetes, despite the presence of microalbuminuria or proteinuria, have normal glomerular structure with or without tubulointerstitial and/or arteriolar abnormalities.…”

Diabetic Kidney Disease

“…The earliest consistent change is thickening of glomerular basement membrane, which is apparent within 1.5-2 years of DM1 diagnosis. It is paralleled by capillary and tubular basement membrane thickening (14,25,26) (Figure 1). Other glomerular changes include loss of endothelial fenestrations, mesangial matrix expansion, and loss of podocytes with effacement of foot processes (Figure 2).…”

“…Other glomerular changes include loss of endothelial fenestrations, mesangial matrix expansion, and loss of podocytes with effacement of foot processes (Figure 2). Mesangial volume expansion is detectable within 5-7 years after DM1 diagnosis (14,25,27,28). Segmental mesangiolysis is observed with progression of diabetes and thought to be associated with development of Kimmelstiel-Wilson nodules and microaneurysms, which often present together (29,30) (Figure 3).…”

Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy

“…The renal lesions in type 1 and type 2 diabetes are similar [2], and involve multiple cell types, including glomerular podocytes, mesangial cells and tubular epithelial cells [3]. Although the glomerulus has been the focus of intensive investigation, recently tubulo-interstitial injury has drawn more attention and interest in diabetic nephropathy research [4,5].…”