PA27.7 | Glomerular Manifestations of Systemic Disease — Summary & Reflection

REFLECT

Before reviewing the summary:

1. Without looking back — can you draw the pathogenesis of diabetic nephropathy linking hyperglycaemia → AGEs → GBM thickening AND intraglomerular hypertension → mesangial expansion → ESRD? Where does microalbuminuria appear on this map?

1. A colleague says "lupus nephritis class V is the dangerous one because it causes the most inflammation." What is the correct statement — which class is the most dangerous, and why does class V cause less acute inflammation despite heavy proteinuria?

1. You are shown a renal biopsy with Congo red-positive deposits and a biopsy with wire-loop lesions. The clinical context is missing. What single clinical/serological test would you order first for each to confirm the underlying systemic disease?

1. In malignant hypertension, the onion-skin lesion and fibrinoid necrosis are both vascular changes. Can you explain, in one sentence each, why they look different and which is which vessel type?

KEY TAKEAWAYS

Glomerular Manifestations of Systemic Disease — Core Points

• Diabetic nephropathy — leading cause of ESRD. Pathogenesis: hyperglycaemia → AGEs + intraglomerular hypertension → GBM thickening + mesangial expansion. Progression: microalbuminuria (stage III) → overt proteinuria (stage IV) → ESRD. Kimmelstiel-Wilson nodular glomerulosclerosis (pathognomonic): ovoid, PAS+, acellular, peripheral mesangial nodules surrounded by patent capillaries. Hyalinosis of BOTH arterioles (efferent involvement virtually unique to DM). IF: non-specific linear IgG (insudative, not immune complex).

• Lupus nephritis — immune complex (anti-dsDNA). ISN/RPS classes I–VI. Class IV (diffuse, ≥50% glomeruli): wire-loop lesions (massive subendothelial deposits), endocapillary proliferation, full-house IF (IgG+IgA+IgM+C3+C4+C1q), crescents in severe cases. Most severe; most responsive to aggressive immunosuppression.

• Amyloidosis — amorphous eosinophilic mesangial/GBM deposits. Diagnosis: Congo red + apple-green birefringence under polarised light. EM: 8–10 nm non-branching fibrils. Dominant presentation: nephrotic syndrome. Commonest cause of death in systemic amyloidosis.

• Benign hypertensive nephrosclerosis — hyaline arteriolosclerosis (afferent + efferent in DM; only afferent in HTN). Finely granular contracted kidney. Slowly progressive CKD.

• Malignant hypertensive nephrosclerosis — fibrinoid necrosis of arterioles + hyperplastic (onion-skin) arteriolitis in interlobular arteries. Flea-bitten kidney. AKI. Medical emergency.

• Others: HSP (IgA dominant mesangial); Goodpasture (linear IgG, pulmonary haemorrhage + RPGN); myeloma (cast nephropathy — fractured casts + giant cells); cryoglobulinaemia (MPGN-like + intraluminal cryoprecipitates); TMA (glomerular microthrombi, MAHA).

• Clinical approach: correlate proteinuria magnitude + urine sediment + GFR trajectory with systemic serology. Proteinuria in diabetic + retinopathy = no biopsy needed. Atypical features (no retinopathy, rapid decline, haematuria, short DM duration) → biopsy to exclude non-diabetic cause.