Renal Digest
HOME
SEARCH
GLOSSARY
HELP
Keyfeatures
Definition
Etiology
Clinical
Histopathology
Immunofluorescence
Electron microscopy
Images
 
  
table of contents » preview  
    Diffuse and nodular diabetic glomerulosclerosis
     Key features:
 
Clinical: Most common cause of end-stage renal disease in the United States, seen in patients with diabetic nephropathy
Light microscopy: Glomerular hypertrophy, diffuse expansion of mesangial matrix with formation of Kimmelstiel-Wilson nodules, microaneurisms, hyaline caps, capsular drops, and arteriolar hyalinosis
Immunofluorescence: Mild diffuse linear IgG and albumin reactivity can be seen along all basement membranes
Electron microscopy: Thickening of basement membranes and nodular expansion of mesangial matrix, in the absence of electron-dense deposits


Definition:  
Diabetic nephropathy is a clinical syndrome associated with long-standing diabetes mellitus and characterized by: persistent albuminuria (>300 mg/d or >200 mcg/min) that is confirmed on at least two occasions three to six months apart, a relentless decline in the glomerular filtration rate (GFR), and hypertension. The pathologic changes seen in patients with diabetic nephropathy include diffuse and nodular glomerulosclerosis, insudative lesions (arteriolar hyalinosis, capsular drop, and fibrin cap), and papillary necrosis.

Differential diagnosis:
Amyloidosis
Monoclonal immunoglobulin deposition disease (MIDD)
Membranoproliferative glomerulonephritis (MPGN), idiopathic, type I
Thrombotic microangiopathy, chronic (CTMA)

Etiology:  
Associated with long-standing and poorly controlled diabetes mellitus {1}. Hyperglycemia, insulin deficiency, hemodynamic factors (hyperfiltration), genetic predisposition, etc., have all been implicated in pathogenesis {2}, {3}

Clinical:  
Microalbuminuria, increasingly severe, progressing into significant and sometimes nephrotic range proteinuria
Microhematuria
Advanced diabetic systemic disease, including retinopathy and hypertension

Histopathology:  
In advanced disease, marked mesangial expansion, with formation of pauci-cellular Kimmelstiel-Wilson nodules in many segments; the nodules are sometimes rather cellular (suggestive of superimposed renal disease of other etiology)
Peripheral capillary loops are diffusely thickened and microaneurysms are frequently seen
Insudation of plasma proteins into the capillary wall (fibrin cap), Bowman's capsule (capsular drop), or vessel wall (hyaline arteriolosclerosis)
Advanced tubular atrophy with thickening of tubular basement membranes, associated with dense interstitial fibrosis and non-specific, predominantly mononuclear cell inflammatory infiltrate
Advanced diabetic renal disease is usually associated with severe vascular sclerosis
Congo red stain is negative

Immunofluorescence:   

      Mild linear reactivity for albumin and IgG along the capillary loops; no immune deposits
  Click here to view table

Electron microscopy:  
Visceral epithelial cells: Focal but sometimes extensive effacement of visceral epithelial cell foot processes, in the absence of electron-dense deposits
Glomerular basement membranes: Irregularly thickened
Glomerular endothelial cells: Various non-specific changes; do not contain tubuloreticular structures
Mesangium: Normal cell elements and nodular expansion of extracellular matrix in the absence of electron-dense deposits
  Please click here to comment
view entire image gallery  

Kimmelstiel-Wilson nodules; note nodular accumulation of acellular matrix in the mesangium of a patient with long-standing diabetes mellitus; HandE, 400x
Kimmelstiel-Wilson nodules in diffuse nodular diabetic glomerulosclerosis; PAS, 200x
Large, sclerotic, argyrophilic mesangial nodules and capillary loop mycroaneurisms.
Nodular mesangial sclerosis
Advanced diffuse and nodular diabetic glomerulosclerosis
Thickened capillary loops and nodular mesangial expansion in diabetic glomerulosclerosis, EM 2,200x
Thickened capillary loops and nodular mesangial expansion in diabetic glomerulosclerosis, EM 2,200x
Diabetic glomerulosclerosis, EM 2,200x
Nodular mesangial expansion by matrix, thickened basement membranes; EM, 2,200x
Diffuse and nodular diabetic glomerulosclerosis, EM 1,400x
Nodular mesangial expansion by matrix, hyaline entrapement, foam cell infiltration; EM, 2,200x
Increase in mesangial matrix in the absence of electron-dense deposits. Capillary loops are irregularly thickened.
Nodular accumulation of mesangial matrix, in the absence of electron-dense deposits. Mesangial cells are aggregated at the periphery of the nodule; EM, 2,200x
Nodular expansion of mesangial matrix in diabetic glomerulosclerosis; EM, 3,500x
Mild linear reactivity for IgG is seen in glomerular and tubular basement membranes. Nodular mesangial expansion can also be appreciated; IF, 200x
Linear reactivity for IgG along the capillary loops. Nodular mesangial expansion; IF, 400x
view entire image gallery  
References :
1. Drummond K, Mauer M; International Diabetic Nephropathy Study Group. The early natural history of nephropathy in type 1 diabetes: II. Early renalstructural changes in type 1 diabetes.Diabetes. 2002 May;51(5):1580-7.  PUBMED  
2. Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy.J Am Soc Nephrol. 2005 Mar;16 Suppl S30-3. Review.  PUBMED  
3. Ayodele OE, Alebiosu CO, Salako BL. Diabetic nephropathy--a review of the natural history, burden, risk factors andtreatment.J Natl Med Assoc. 2004 Nov;96(11):1445-54. Review.  PUBMED