Systemic Disease Affecting the Kidneys

Question 1

Describe the pathophysiology of diabetic nephropathy

Answer 1

• hyperglycaemia
• volume expansion in afferent arteriole
• intra-glomerular hypertension and thickening of vessel walls
• hyperfiltration at the glomerulus
• proteinuria (due to vessel wall damage)
• hypertension and renal failure

Question 2

Describe the changes to the glomeruli in diabetes

Answer 2

• thickening of BM then progressive loss
• fusion of foot processes
• loss of podocytes
• mesangial matrix expansion
• nodule infiltration

Question 3

Describe the clinical presentation of diabetic nephropathy

Answer 3

• usually after 20y diabetes (be aware of delayed diagnosis)
• always in association with other diabetic complications (eg. retinopathy) and proteinuria = rise in creatinine as well

Question 4

Describe the management of diabetic nephropathy

Answer 4

1. treat hypertension: ACEi/ARB, low salt diet, weight management and exercise
2. improve blood glucose control: education, drugs (eg. insulin, SGLT2I - empagliflozin)

Question 5

Describe the action of SGLT2I

Answer 5

• act on the glomerulus to decrease intraglomerular pressure and normalisation of GFR
• decreases glucose and Na+ absorption in tubules
• increased Na+ delivery to JGA
• only for type II diabetics

Question 6

Describe the pathogenesis of renovascular disease

Answer 6

-progressive narrowing of renal arteries with atheroma
- perfusion of kidney falls, GFR falls but tissue oxygenation of cortex and medulla maintained
- RA stenosis progresses and cortical hypoxia and microvascular damage ensues with activation of inflammatory and oxidative pathways
- parenchymal inflammation and fibrosis becomes irreversible

Question 7

Describe the management of renal artery stenosis

Answer 7

• medical = BP control (not ACEi/ARB), stain, good glycemic control if diabetic
• lifestyle = smoking, exercise, low Na+ diet
• angioplasty (for rapidly deteriorating renal failure, uncontrolled hypertension on multiple agents, flash pulmonary oedema)

Question 8

What is amyloidosis?

Answer 8

• deposition of highly stable insoluble proteinaceous material in extracellular space (made up of beta-pleated sheets)
• deposits in kidney, liver, heart, gut
• 8-10nm fibrils on electron microscopy = mesangial expansion
• Congo red stain (light microscopy) = apple green birefringence

Question 9

What are the 2 classes of amyloidosis?

Answer 9

• AA: systemic (infection/inflammation)
• AL: immunoglobulin fragments from haematological condition (eg. myeloma)

Question 10

What is the management of amyloidosis?

Answer 10

• AA: treat underlying source of infection/inflammation
• AL: treat underlying haematological condition

Question 11

Describe the pathogenesis of myeloma renal disease

Answer 11

• cast nephropathy
• hypercalcaemia/dehydration
• amyloid
• light chain deposition disease
• acquired Fanconi syndrome (proximal tubule dysfunction from antibody toxicity)

Question 12

What are the principles of treatment for systemic disease involving the kidneys?

Answer 12

1. treat underlying condition
2. treat BP
3. treat other vascular risk factors

Question 13

Describe the pathogenesis of lupus nephritis

Answer 13

• autoantibodies against dsDNA or nucleosomes
• form intravascular immune complexes or attach to GBM
• activate complement (consume C4)
• renal damage