8. Diabetic nephropathy

Question 1

what is diabetic nephropathy

Answer 1

kidney damage caused by excess plasma glucose filtration into urine at glomerulus

Question 2

name the 5 stages of diabetic nephropathy - how does GFR change throughout

Answer 2

1. hyperfiltration - GFR increases
2. latent stage - GFR peaks
3. microalbuminuria - GFR returns to normal levels
4. overt proteinuria- GFR decreases
5. end-stage renal disease - very low GFR

Question 3

why does hyperfiltration occur in stage 1

Answer 3

i. increased glucose reabsorption in PCT via SGLT2 upregulation - also increases Na reabsorption…
ii. decreased Na reaching macula densa in DCT… activation of JGA:
- afferent arteriole vasodilation
- RAAS activation… increased AngII and efferent arteriole vasoconstriction
iii. increased GFR and hyperfiltration

Question 4

which changes occur in the kidney during stage 2

Answer 4

high pressure state causes supportive mesangial cells to secrete more structural matrix… increased glomerular size - kidney hypertrophy

Question 5

in stage 3, why does:

• albuminuria occur
• GFR return to normal

Answer 5

i. continued mesangial expansion and matrix deposition… not uniform so creates Kimmelstiel-Wilson nodules, i.e. glomerular sclerosis

ii. thickening of GBM… increased filtration slits between podocyte foot processes - podocyte disruption… increased permetability…
- albuminuria
- decreased filtration surface area… decreased GFR

Question 6

which changes occur in stage 4

Answer 6

1. diffuse glomerular histopathological changes/damage… further decreased GFR and severely increased albuminuria
2. worsening systemic hypertension: excess plasma glucose causes glycation of arteriole BM - hyaline arteriosclerosis… decreased blood flow and increased BP. Affects nerves, eyes and renal arterioles… tissue ischaemia.

Question 7

what are the likely causes of death in diabetic nephropathy

Answer 7

• mainly CVD: diabetic nephropathy confers increased CVD risk (10 fold risk once proteinuria has occured)
• in some: ESRD

Question 8

why is RAAS inhibition important in management of diabetic nephropathy

Answer 8

AngII release following RAAS activation leads to:

• increased glomerular permeability to proteins
• mesangial cell proliferation and increased mesangial matrix
• efferent glomerular constriction… increased glomerular pressure