Systemic Diseases Affecting the Kidney
Diabetic Nephropathy
• Pathophysiology: Glomerular hyperfiltration → mesangial expansion, basement membrane thickening, glomerulosclerosis
• Progression:
Microalbuminuria → overt proteinuria → ↓ eGFR → ESRD
• Investigations:
ACR (albumin:creatinine ratio), eGFR monitoring
• Histology: Kimmelstiel–Wilson nodules (nodular glomerulosclerosis)
• Management:
o Tight BP control (target <130/80)
o RAAS blockade (ACEi/ARB) even if normotensive
o Glycaemic control
Hypertensive Nephropathy
• Mechanism: Arteriolar thickening → glomerulosclerosis → ischaemia → small scarred kidneys
• Types:
o Benign nephrosclerosis: gradual, seen in essential HTN
o Malignant HTN: rapid decline in renal function, haematuria, fibrinoid necrosis
• Features: Proteinuria, slowly progressive CKD
• Diagnosis: Small, echogenic kidneys on ultrasound
• Management: BP control (ACEi/ARB preferred)
Amyloidosis
• Pathology: Deposition of amyloid fibrils (AL or AA) in glomeruli
• Features:
o Nephrotic syndrome
o Hepatomegaly, cardiac involvement, neuropathy
• Diagnosis:
o Renal biopsy: apple-green birefringence with Congo red stain
o Serum free light chains (AL), SAP scan
• Management:
o Treat underlying cause (e.g. myeloma)
o Supportive care: diuretics, ACEi
Myeloma Kidney (Cast Nephropathy)
• Pathophysiology: Light chains (Bence–Jones proteins) precipitate in tubules → tubular obstruction and toxicity
• Features:
o AKI or CKD
o Minimal proteinuria on dipstick (light chains not detected)
• Diagnosis:
o Urine Bence–Jones proteins, serum free light chain assay
o Bone marrow biopsy
• Management: Chemotherapy, hydration, avoid nephrotoxins
SLE Nephritis
• Lupus nephritis occurs in up to 50% of patients with SLE
• Class IV (Diffuse proliferative) is the most severe
• Diagnosis:
o ANA, anti-dsDNA, ↓ C3/C4, proteinuria, haematuria
o Confirm with renal biopsy
• Management:
o Immunosuppression: steroids + cyclophosphamide or mycophenolate mofetil (MMF)
o Hydroxychloroquine in all SLE patients unless contraindicated
ANCA-Associated Vasculitis
1. Granulomatosis with Polyangiitis (GPA)
• c-ANCA (anti-PR3)
• Triad: ENT (sinusitis, nasal crusting), lungs (nodules, haemoptysis), kidneys (RPGN)
• Rx: steroids + cyclophosphamide or rituximab
2. Microscopic Polyangiitis (MPA)
• p-ANCA (anti-MPO)
• Renal-predominant or renal + lung involvement (alveolar haemorrhage)
• Similar Rx to GPA
Goodpasture’s Syndrome
• Anti-GBM antibodies against type IV collagen in glomerular and alveolar basement membranes
• Features:
o Pulmonary haemorrhage + RPGN (haematuria, AKI)
• Diagnosis:
o Anti-GBM antibody, linear IgG on biopsy
• Management:
o Plasmapheresis + steroids + cyclophosphamide
Thrombotic Microangiopathy (TMA)
• Pathophysiology: Endothelial injury → microvascular thrombosis → AKI, MAHA, thrombocytopenia
• Conditions:
o HUS (often post-E. coli O157:H7): renal predominant
o TTP (ADAMTS13 deficiency): fever, neuro signs, low platelets, MAHA, renal dysfunction
• Diagnosis:
o Schistocytes, ↑ LDH, ↓ haptoglobin
o ADAMTS13 assay (if TTP suspected)
• Management:
o HUS: supportive
o TTP: plasmapheresis, avoid platelet transfusion
Cryoglobulinaemic Glomerulonephritis
• Assoc.: Chronic hepatitis C, autoimmune disease, lymphoproliferative disorders
• Mechanism: Immune complex deposition → membranoproliferative GN
• Features: Proteinuria, haematuria, purpura, arthralgia, neuropathy
• Diagnosis:
o Cryoglobulin levels, ↓ C4, positive RF
• Management:
o Antivirals (if HCV), immunosuppression in severe disease
Renal Sarcoidosis
• Mechanism: Non-caseating granulomas → interstitial nephritis ± nephrocalcinosis
• Features:
o Hypercalcaemia (↑ 1α-hydroxylase activity in granulomas)
o AKI or chronic tubulointerstitial disease
• Diagnosis: Renal biopsy showing granulomas
• Management: Corticosteroids
