Diabetic nephropathy
- Lesion
High glucose slowly thickens basement membranes and fills the mesangium with matrix; diabetes is the top cause of kidney failure.
What it is
Diabetic kidney disease develops over years in both type 1 and type 2 diabetes. Advanced glycation end products, glomerular hyperfiltration, angiotensin II and TGF-β drive matrix build-up in basement membranes and mesangium, while hyaline arteriolosclerosis narrows both afferent and efferent arterioles. The disease also makes the kidney prone to pyelonephritis and papillary necrosis.
Structure
- Kidneys normal or large early, finely granular and small late.
- Kimmelstiel-Wilson nodules: round, PAS-positive acellular matrix balls at the periphery of the tuft, often with microaneurysms.
- IF: linear staining for IgG and albumin along membranes from nonspecific trapping, not immune deposits.
- Tubular basement membranes thicken and the interstitium scars; Armanni-Ebstein glycogen vacuoles in tubules with marked hyperglycemia.
Step by step
- Chronic hyperglycemia glycates matrix proteins and forms advanced glycation end products.
- Efferent arteriole constriction by angiotensin II and hyperfiltration raise glomerular pressure.
- Mesangial cells, stimulated by TGF-β, make excess collagen IV and matrix; the GBM thickens.
- Podocytes are lost and albumin starts to leak (moderately increased albuminuria).
- Mesangial expansion compresses capillaries and forms nodules; proteinuria grows.
- Hyaline arterioles, sclerosed glomeruli and interstitial fibrosis reduce GFR to end-stage disease.
Clinical notes
- Annual screening for urine albumin and eGFR in diabetes detects disease early.
- Retinopathy usually coexists; its absence with nephrotic proteinuria should prompt a search for another glomerular disease.
Test yourself
Think of the answer, then tap the question to see it.
What is the earliest morphologic change of diabetic nephropathy?
Thickening of the glomerular basement membrane, visible by electron microscopy.
What are Kimmelstiel-Wilson lesions?
Nodules of PAS-positive mesangial matrix at the periphery of the glomerular tuft in diabetes.
Which arterioles show hyalinosis in diabetes?
Both afferent and efferent arterioles; hypertension mainly affects the afferent.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Diabetes and kidney disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Chronic Kidney Disease (StatPearls (NCBI Bookshelf), 2024).
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Representative model, for educational purposes only.