Diabetic nephropathy

Question 1

List some DDx for nephrotic syndrome?

Answer 1

According to 3 glomerular layers:

1) Podocytes- podocyte effacement, nil immune complex depositions
- minimal change disease (idiopathic, HL)
- focal segmental glomerular sclerosis (idiopathic, HIV, heroin, sickle cell disease)
2) Basement membrane- thickened membrane, immune complex deposits
- membranous nephropathy (idiopathic, HBV, HCV, SLE, NSAIDs)
- membranoproliferative glomerulonephritis (HBV, HCV)
3) Fenestrated epithelium
a) Diabetes:
- hyperglycaemia -> glycosylation of vascular GBM -> leaky walls -> protein leaks into BV wall -> hyaline arteriolosclerosis -> decreased lumen
- efferent arteriole sclerosis -> glomerulus back pressure -> hyperfiltration -> microalbuminuria
b) Systemic amyloidosis

Question 2

List some differentials for nephritic syndrome?

Answer 2

• acute post-strep GN
• rapidly progressive GN
• diffuse proliferative GN
• IgA nephropathy
• Alport syndrome
• membranous proliferative GN

Question 3

What investigations would you do?

Answer 3

Diagnostic:
- urinalysis: protein, glucose
- 24hr urine collection: protein >3.5g/day
- renal biopsy: mesangial expansion, GMB thickening, podocyte effacement, glomerular sclerosis
Labs:
- HbA1c/BSL
- EUC, eGFR
- LFT: hypoalb
- Coags: hypercoagulable (due to hypoalb)
- Lipids: hypercholesterolaemia 
- ANA: SLE (membranous nephropathy)
- Complement: MPGN
- HIV screen: FSGN
- Blood film: sickle cell (FSGN)
- Urine monoclonal protein: amyloidosis
- D-dimer: PE
Imaging:
- Renal US: initially large
- CT abdo: hydronephrosis possible
- Dopple US: renal artery stenosis, DVT
- ECG: acute cardiac failure (cause oedema)

Question 4

Describe the glomerular filtration barrier structure and function?

Answer 4

Structure:
4 main layers (from blood to urine side):
1) endothelial surface layer: restricts plasma flow, can exclude RBCs
2) fenestrated endothelium
3) basement membrane: collagen, glycoproteins
4) podocytes: cells w foot processes and slits inbetween
Mesangial cells lie between capillaries -> structural support

Function:

• maintain glomerular pressure (afferent and efferent arterioles)
• glomerulus allows passage of small ions (Na and K)
• normally impermeable to proteins (negative charge of GBM and pore size)

Question 5

Describe the pathophysiology of diabetic nephropathy?

Answer 5

1) Glomerular HTN: hyaline arteriolosclerosis in efferent glomerular arterioles -> inceased back pressure -> glomerular HTN and hyperfiltration
2) glycosylation of GBM -> podocyte effacement -> increased permeability
3) basement thickening: collagen deposition
4) osmotic damage: glucose -> sorbitol (via aldose reductase) -> diffuse into cells -> cell swelling and death

Question 6

Why does diabetic nephropathy cause oedmea and lipid changes?

Answer 6

Oedema: increased glomerular permeability -> albuminuria -> hypoalbuminaemia -> lowers plasma colloid osmotic pressure -> transcapillary filtration of water -> oedema

Hyperlipidaemia: hypoalbuminaemia -> stimulates cholesterol synthesis by liver

Question 7

What is the starling equation?

Answer 7

Starling equation: describes flux of water across capillary wall

1) attraction of water TOWARDS area of higher oncotic pressure
2) attraction of water away from areas of higher hydrostatic pressure
3) membrane permeability

Equation:
oedematous flow= (cap hydrostatic pressure - insterstitial hydrostatic pressure) - (cap oncotic pressure- interstitial oncotic pressure)