Risk of Coronary Artery Disease

in Nephrotic Syndrome

Presenter: Dr. Sudhesna

Moderator: Dr. B.C Koner

 Features of Nephrotic Syndrome
• Proteinuria: > 3g/day
• Hypoalbuminemia
• Edema
• 2g protein per gram of urinary creatinine
• Clinical features:
 Etiology
• Primary causes:
1) MCD
2) Focal glomerulosclerosis
3) Membranous nephropathy
4) Hereditary nephropathies
• Secondary causes:
1) Diabetes Mellitus
2) Lupus erythematosus
3) Amyloidosis & paraproteinemias
Albumin Metabolism in N.S :
 Albumin metabolism in NS
• Nephrotic hypoalbuminemia occurs due to:
• Urinary loss
• Decreased or insufficiently increased hepatic
albumin synthesis: Hepatic albumin synthesis
is directly determined by changes in the
hepatic extravascular interstitial albumin pool
than by plasma characteristics.
• Increased albumin catabolism
 CAD risk factors:
Conventional risk factors:
•Dyslipedemia
•Hypertension
•Smoking
•DM
•Obesity
•Family History
Non-conventional risk factors:
•Hyperhomocysteinuria
•Thrombogenic Factors
•Inflammatory markers
•Impaired fasting glucose
Pathogenesis of nephrotic hyperlipidemia
• Alterations in VLDL:
• Increased synthesis- “increase in level of
apo B mRNA in hepatocytes in hypo-
oncotic medium”
• Reduced LPL activity –
• 1) Increased excretion of heparan sulfate
(excretion of GAGs in urine)
2) decreased synthesis of heparan sulfate
(loss of orosomucoid)
3) Increased availability of FFA
4) Apo E and Apo C is reduced-affects
LPL mediated clearance of VLDL.
Alterations in LDL:
• Absolute increase in apoB100 synthesis
•Increased levels and activity of CETP
•Down regulation of LDL receptors
decreasing clearance
•Defect in recognition by LDL receptor
Alterations in HDL:
•Diminished activity of LCAT due to loss in
urine
•Hypoalbuminemia increases levels of free
lysolecithin which is an inhibitor of LCAT
•Increased activity of CETP
 Lipoprotein A
•Lp-a elevations are due to increased synthesis
(inversely proportional to plasma albumin
levels)
Increase in cholesterol synthesis :
•Increased availability of mevalonic acid
•Increased activity of HMG-CoA reductase
•Decreased expression of cholesterol 7 alpha
hydroxylase
•ACAT upregulation leads to intracellular
accumulation of cholesterol ester. It leads to
foam cell formation.
Pathogenesis of hypercoagulability
• Increased levels of fibrinogen and cofactors
5,8 - increased hepatic synthesis.
• Fibrinogen levels correlate with urinary
protein and serum cholesterol level :
Hyperfibrogenemia determines thrombotic
risk
• Urinary loss of low molecular weight
anticoagulants
Pathogenesis of hypercoagulability
 Alterations in platelet function
• Platelet aggregation: Elevation in Beta
thromboglobulin which is released by
platelets on aggregation.
• Other factors :
• Steroid therapy
 Role of homocysteine
• Controversial
• Increased free Hcy concentration because of
decreased binding with albumin.
 Role of oxidative stress
• Reduced free radical trapping in N.S :
positively correlated with serum albumin
levels.
• There is increase in oxidised LDL which is
converted to lysophosphatidyl choline and
oxidised fatty acids by Lp PLA2 - atherogenic
 Endothelial dysfunction
• Increased nonprotein bound NEFAs :
increased endothelial toxicity
decreased NOS activity
To summarize…
THANK YOU
 Pathogenesis

• Effacement of the foot processes of the GBM

• Loss of negative charges on the GBM
• Pathophysiology of nephrotic syndrome