Franco Ferrario and Maria Pia Rastaldi
Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Renal involvement in type 2 diabetes is a well-known clinical occurrence.
According to data from literature, type 2 diabetes presents various changes, including glomerulosclerosis, non-specific chronic damage mostly related to vascular changes and glomerular diseases superimposed on, or even unrelated to, diabetic glomerulosclerosis.
In recent research carried out by the Italian Group of Renal Immunopathology, 674 patients with type 2 diabetes who had undergone renal biopsy for a morphological definition of renal disease were studied.
Cases presented different morphological features and were divided into four histological classes: class 1, diabetic glomerulosclerosis (309 cases; 45,8%); class 2, chronic changes mostly related to vascular damage (91 cases; 13,5%); class 3a, glomerular diseases superimposed on diabetic glomerulosclerosis (106 cases; 15,7%); class 3b, other glomerulonephritis without the presence of diabetic lesions (164 cases; 24,3%). In this “Renal Pathology Learning” we will describe the morphological features of classic diabetic glomerulosclerosis (class 1).
The early phases of diabetic nephropathy are characterized by mild mesangial matrix expansion, without thickening of the basement membrane. When the nephritic syndrome is clinically present, differential diagnosis from minimal change disease has to be made. More commonly, a more severe mesangial expansion accompanied by basement membrane thickening can be detected, and a differential diagnosis has to be made from idiopathic membranous glomerulonephritis.
Nodular lesions were the morphological change first recognized by Kimmelstiel and Wilson (1936).
These are typically characterized by the accumulation of homogeneous eosinophilic material within the mesangium, appearing as a rounded accentuation of the mesangial expansion usually acellular and strongly PAS positive.
The individual nodules vary considerably in size and their number varies from one patient to another and from one glomerulus to another.
The most common pattern is diffuse and marked nodular glomerulosclerosis, similar to other nodular forms of nephritis, such as type I Membranoproliferative Glomerulonephritis, Amyloidosis and Light Chain Deposition Disease
In other cases, the nodules can be larger and isolated.
It is well-known that the nodules may originate in relation to microaneurysms, wherein the glomerular basement membrane loses its anchoring point to the mesangial stalk.
Such microaneurysms may arise in association with mesangiolysis, accompanied by disintegration of the mesangial matrix and compaction of mesangial material resulting in the formation of several layers of fibrillary material and nodule formation.
In some cases, an intense increase of mesangial matrix, without nodule formation, characterizes a pattern of diffuse diabetic glomerulosclerosis.
In few cases, a marked mesangial proliferation is present in association with diffuse glomerulosclerosis, and a differential diagnosis has to be made from idiopathic membranoproliferative glomerulonephritis and diffuse lupus nephritis.
Some other glomerular lesions can be considered which, if not diagnostic, are nonethless highly suggestive for diabetic nephropathy: glomerular hypertrophy probably due to glomerular hyperfiltration; subendothelial deposition of hyaline material (fibrin cap); hyaline material deposited in the Bowman's capsule (capsular drop).
Another typical feature of diabetic nephropathy is the presence of arteriolar sclerohyalinosis.
Immunofluorescence can be completely negative or show a linear deposition of IgG along the glomerular capillaries and the tubular basement membranes.
Depending on the intensity of the IgG linear deposits, a differential diagnosis may have to be made from anti-glomerular basement membrane antibody disease.
Electron microscopy confirms the thickening of the basement membrane, and in the nodular form mesangial matrix expansion and sclerosis with some mesangial cell entrapment.
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