Systemic Diseases Affecting the Kidneys

Question 1

What is the pathophysiology of diabetic nephropathy?

Answer 1

• Hyperglycaemia > volume expansion > intra-glomerular HTN > hyperfiltration > proteinuria > HTN and renal failure

Question 2

How does diabetic nephropathy present?

Answer 2

• Proteinuria, HTN and renal failure
• Histology shows thickening of GBM, fusion of foot processes, loss of podocytes with denuding of the GBM, mesangial matrix expansion and nodular glomerulosclerosis (‘Kimmelstiel-Wilson kidney)

Question 3

How is diabetic nephropathy managed?

Answer 3

• Better glucose control
• Better BP control
• Blockade of the RAAS system

Question 4

What is the pathophysiology of vascular disease affecting the kidneys?

Answer 4

• Progressive narrowing of renal arteries with atheroma
• Prefusion falls by 20%, GFR falls but tissue oxygenation of cortex and medulla maintained
• RA stenosis progresses to 70%, cortical hypoxia causes microvascular damage and activation of inflammatory and oxidative pathways
• Parenchymal inflammation and fibrosis progress and become irreversible, restoration of blood flow provides no benefit

Question 5

How does vascular disease of the kidneys present and how is it managed?

Answer 5

• Clinical diagnosis (nor vasculitis/GN/diabetic nephropathy as no protein in urine)
• Treated with medication (BP control but not ACE-I/ARB, statin and good glycaemic control) and angioplasty

Question 6

What is the pathophysiology of amyloidosis?

Answer 6

• Deposition of highly stable insoluble proteineous material in extracellular space (felt-like substance made of beta-pleated sheets)
• Specific ultrastructural features (8-10nm fibrils)
• High affinity for the constituents of the capillary wall
• Two classes; AA (systemic amyloidosis - inflammation/infection) and AL (immunoglobulin fragments from haematological condition - e.g. myeloma)

Question 7

How does amyloidosis present in the kidneys and how is it treated?

Answer 7

• Nephrotic syndrome
• Congo red stain: apple green birefringence on light microscopy
• Amyloif fibrils cause mesangial expansion on electron microscopy
• AA = treat underlying source of inflammation/infection
• AL = treat underlying haematological condition

Question 8

What is the pathophysiology of lupus?

Answer 8

• Autoimmune disease
• Multiple autoantibodies – directed against DNA, histones, snRNPs, transcriptional/translational machinery
• Auto-antibodies produced against dsDNA or nucleosomes (anti-dsDNA, anti-histone)
• Form intravascular immune complexes or attach to GBM
• Activate complement (low C4)

Question 9

How does lupus present in the kidneys and how is it treated?

Answer 9

• Nephritic syndrome
• Treat with immunosuppression (steroids/MMD/cyclophosphamide/rituximab)

Question 10

How does ANCA-associated vasculitis present int he kidneys and how is it managed?

Answer 10

• Nephritic syndrome
• Management invovles ITU (ventilatory support) and antibody removal/depletion (methylprednisolone, plasma exchange and cyclophosphamide)