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.

Figures

Figure 1

Glomerulus from a type 1 diabetic (T1DM) patient with diffuse (long thick arrow) and nodular (short thick arrow) mesangial expansion and afferent (double thin arrows) and efferent (single thin arrow) arteriolar hyalinosis [Periodic Acid Schiff’s (PAS) stain].

Figure 2

Glomerulus from a T1DM patient with nodular (Kimmelstiel-Wilson) lesions. Note the palisading of nuclei at the periphery of the nodules, the central matrix accumulation, and the restriction of the surrounding glomerular capillaries (PAS). Reprinted with permission from: Parving H-H, Mauer M, Ritz E. Diabetic nephropathy. In: Brenner & Rector’s The Kidney, 7th Ed., Bremer BM (Ed). Saunders, Elsevier’s Health Sciences Department, Philadelphia, 2004, pp. 1777–1818.

Figure 3

Serial sections through a glomerulus with an abnormal glomerular tubular junction with no observable glomerular opening (ATNO) into the proximal tubule (thick yellow arrows). Note the associated Bowman’s capsule abnormalities (thin yellow arrows) and the adhesion of a nodular lesion at the GTJ (images b and c). Acapsular drop (teal arrows, images c and d) is also present (PAS). Reprinted with permission from J Am Soc Nephrol 14:908–917, 2003.

Figure 4

Renal biopsy from a T2DM patient with mild mesangial expansion relative to the severity of interstitial fibrosis (long arrow) and tubular atrophy (short arrow). This would be classified as Category III (PAS).

Figure 5

Renal biopsy from a T2DM patient with hyalinosis of the afferent (right thin arrow) and efferent (left thin arrow) glomerular arterioles, interstitial expansion (short thick arrow) and tubular atrophy (long thick arrow). This would be classified as Category III (PAS).

Figure 6

Diffuse and nodular mesangial expansion in a T1DM patient prior to pancreas transplantation alone (PTA) (PAS). Reprinted with permission from N Engl J Med 339:69–75, 1998.

Figure 7

Persistence of diffuse and nodular mesangial expansion 5 years after successful PTA in the same patient as in Figure 6. Reprinted with permission from N Engl J Med 339:69–75, 1998.

Figure 8

Marked reduction in mesangial expansion 10 years after successful PTA in the same patient as in Figures 6 and 7. Note the persistence (arrow) of arteriolar hyalinosis, a common finding in these cases (PAS). Reprinted with permission from N Engl J Med 339:69–75, 1998.

Figure 9

Moderate to advanced diabetic glomerulopathy despite near normal tubules and interstitium in this T1DM patient prior to PTA (PAS).

Figure 10

Persistence of the diabetic glomerulopathy changes and de novo interstitial fibrosis and tubular atrophy 5 years after PTA in the same patient as in Figure 9 (PAS). Reprinted with permission from Kidney Int 69:907–912, 2006.

Figure 11

Near normalization of glomerular structure, marked resolution of interstitial fibrosis and presumed resorbtion of atrophic tubules 10 years after PTA in the same patient as in Figures 9 and 10.