Diabetic nephropathy causes pathologic abnormalities in all of the major structural compartments of the kidney, including the glomeruli, extra-glomerular vessels, interstitium, and tubules (3-10).
The earliest glomerular change is enlargement (hypertrophy, hyperplasia, glomerulomegaly), which corresponds to the early clinical phase of elevated glomerular filtration rate. By the time albuminuria is detectable, there is generalized thickening of glomerular basement membranes (GBMs) and an increase in mesangial matrix material. In the earliest phase, morphometry is required to detect these changes, but eventually the GBM thickening and mesangial expansion is so pronounced that it can be readily discerned by routine light microscopy, especially if a special stain that accentuates collagenous structures is used [e.g., periodic acid-schiff (PAS), Jones silver, Masson trichrome]. Mild mesangial hypercellularity occasionally accompanies the matrix expansion; thus, care must be taken
not to misdiagnose early diabetic glomerulosclerosis as mesangioprolifera-tive glomerulonephritis.
Overt glomerular mesangial matrix expansion (glomerulosclerosis) manifests as diffuse mesangial matrix expansion or nodular mesangial matrix expansion or, most often, a combination of both (Figs. 12.1 to 12.5).
Figure 12.4. Glomeru-lus from patient with diabetic glomeruloscle-rosis showing a large K-W nodule with vague lamination (PAS stain).
Figure 12.5. Glomeru-lus from patient with diabetic glomeruloscle-rosis showing extensive capillary aneurysm formation as a result of mesangiolysis that has released the GBM from the mesangium (Jones silver stain).
Glomerular basement membrane thickening usually accompanies the mesangial matrix expansion, but it may be somewhat discordant in severity (4). The designations diffuse versus nodular glomerulosclerosis are primarily of descriptive value in the biopsy report and have no value in the diagnosis because the distinctions do not have clinical significance.
Diffuse diabetic glomerulosclerosis is less specific for diabetic glomerulosclerosis than nodular diabetic glomerulosclerosis. Especially if the clinical presence of diabetes is not known and there is accompanying mesangial hypercellularity, the light microscopic changes can be mistaken for a mesangioproliferative glomerulonephritis. Careful examination may reveal early mesangial nodules, which will suggest the correct diagnosis.
The nodular lesions of diabetic glomerulosclerosis were first described by Kimmelstiel and Wilson (3) and thus are called Kimmelstiel-Wilson (K-W) nodules. The nodules begin in the heart of the mesangial region of a segment. As the nodule of matrix accrues, there may be increased numbers of mesangial cells, especially at its leading edges (Fig. 12.1). The nodules often are focal and segmental, although occasional specimens have rather diffuse global nodularity. The nodules have the same tinctorial properties as normal mesangial matrix, and thus are PAS and silver positive (Figs. 12.3 to 12.5). The matrix at the center of the nodules may be homogeneous or laminated (Fig. 12.4). K-W nodules may have a corona of capillary aneurysms that are formed as a result of mesangiolysis, which disrupts the attachment points of the GBM to the mesangium (Fig. 12.5).
Glomerular hyalinosis is common in diabetic glomerulosclerosis. These hyaline lesions may result from insudation or exudation of plasma proteins from vessels followed by entrapment in matrix. The hyalinosis can occur anywhere in the tuft, but there are two characteristic patterns: hyaline caps and capsular drops. The hyaline caps are produced when the hyalinosis forms arcs at the periphery of segments, sometimes appearing to fill the capillary aneurysms. Capsular drops are spherical accumulations of hyaline material adjacent to or within Bowman's capsule.
Crescent formation is identified in < 5% of specimens with diabetic glomerulosclerosis (Fig. 12.6). When crescents are observed, one should consider the possibility of a concurrent glomerulonephritis that is more often associated with crescents, such as antineutrophil cytoplasmic antibodies (ANCA) disease or anti-GBM disease.
Diabetic glomerulosclerosis is caused by both type 1 (IDDM) and type 2 (NIDDM). The latter is somewhat more heterogeneous in appearance (5,8), in part because it often is altered by concurrent hypertensive and aging changes. At a comparable stage of diabetic nephropathy, the glo-merular lesions in type 2 diabetes tend to be less severe than those in type
Arteriolosclerosis and arteriosclerosis are typical accompaniments to diabetic glomerulosclerosis. Arteriolar hyalinosis at the glomerular hilum
is ubiquitous with diabetic glomerulosclerosis and typically affects both the afferent and efferent arterioles (10). Hypertensive hyaline arteriolar sclerosis affects the afferent but not efferent arteriole.
The earliest tubular change is thickening of tubular basement membranes (TBMs) that is analogous to the GBM thickening (Fig. 12.7). With
progressive chronic disease, tubules become atrophic and the interstitium develops fibrosis and chronic inflammation. Except for the marked TBM thickening, these chronic tubulointerstitial changes resemble those seen with any form of progressive glomerular disease.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...