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