Systemic Diseases Affecting the Kidney

Question 1

Diabetic Nephropathy

1. pathophysiology? [7]
2. histology? [1]
3. presentation? [5]
4. management? [4]

Answer 1

1. pathophysiology:
   
   • hyperglycaemia leads to increased growth factors, RAAS activation, production of advanced glycosylation end-products and oxidative stress
   • this causes increased glomerular capillary pressure, podocyte damage and endothelial dysfunction
2. histology:
   
   • pathognomic hyaline material containing nodules (excess mesangial matrix) in glomerular capillary loops
3. presentation:
   
   • albuminuria = 1st sign
   • later, scarring (glomerulosclerosis)
   • nodule formation
   • fibrosis with progressive loss of renal function
4. management:
   
   • intensive glycaemic control - insulin/SGLT2 inhibitors etc.
   • ACE inhibitor/ARB
     
     • CV protection → reduces BP
     • renal protection → reduces efferent arteriole constriction → reduces glomerular pressure
   • sodium restriction
   • statins

Question 2

Renovascular disease:

1. pathophysiology? [7]
2. presentation? [4]
3. differentials? [3]
4. management? [5]
5. when to do an angioplasty? [3]

Answer 2

1. pathophysiology:
   
   • progressive narrowing of renal arteries with atheroma
   • perfusion falls by 20% and GFR falls but tissue oxygenation of cortex & 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 irrreversible
   • restoration of blood flow provides no benefit
2. presentation:
   
   • raised BP
   • raised lipids
   • acute decompensated heart failure (with no LV impairment on echo)
   • flash pulmonary oedema (in 10%)
3. differentials:
   
   • obstruction
   • renal artery stenosis
   • interstitial nephritis
4. management:
   
   • BP control (but not with ACEi or ARB)
   • statins
   • if diabetic, good glycaemic control
   • smoking cessation and exercise
5. do an angioplasty for:
   
   • rapidly deteriorating renal failure
   • uncontrolled raised BP on multiple agents
   • flash pulmonary oedema

Question 3

Amyloidosis

1. definition? [1]
2. investigations? [2]
3. describe the 2 classes? [2]
4. treatment? [2]

Answer 3

1. deposition of highly stable insoluble proteineous material made of beta-pleated sheets in extracellular space of kidney, heart, liver and gut
2. diagnose using:
   
   • light microscopy (Congo red stain)
   • electron microscopy
     
     • show amyloid fibrils causing mesangial expansion
3. the 2 classes:
   
   • AA = systemic amyloidosis caused by inflammation/infection
   • AL = immunoglobulin fragments from haematological conditions e.g. myeloma
4. treatment:
   
   • AA amyloid → treat the underlying source of inflam/infection
   • AL amyloid → treat the underlying haematological condition

Question 4

Systemic Lupus Erythematosis (SLE)

1. definition? [1]
2. pathophysiology? [4]
3. presentation? [1]
4. diagnosis? [1]
5. treatment? [4]

Answer 4

1. systemic autoimmune disease - immune complex mediated glomerular disease
2. pathophysiology:
   
   • autoantibodies are produced against dsDNA or nucleosomes (anti-dsDNA, anti-histone)
   • form intravascular immune complexes or attach to glomerular basement membrane
   • activate complement
   • results in renal damage
3. presentation:
   
   • various systemic symptoms including renal disease
4. diagnosis by renal biopsy
5. treatment:
   
   • immunosuppression:
     
     • steroids
     • MMF
     • cyclophosphamide
     • rituximab