Insulin resistance, dyslipidaemia, inflammation and endothelial function in nephrotic syndrome.
BACKGROUND
Nephrotic syndrome (NS) is associated with an increased risk of cardiovascular disease (CVD). We have shown previously that endothelial function, measured by post-ischaemic flow-mediated dilatation (FMD) of the brachial artery, is impaired in NS. In this study our aim was to assess the potential roles of insulin resistance, plasma non-esterified fatty acids (NEFAs) and inflammation in endothelial dysfunction in NS patients.


METHODS
FMD was compared between NS patients (n=19) and controls (CS, n=19). Plasma glucose, insulin and NEFAs were measured. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) score. C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and fibrinogen were measured as markers of inflammation.


RESULTS
FMD was significantly lower in the NS group (mean+/-standard error, NS 5.1+/-0.7%, CS 7.3+/-0.7%, P=0.02). Fasting insulin (NS 12.5+/-1.5 mU/l, CS 6.8+/-0.7 mU/l, P<0.01), fasting glucose (NS 5.3+/-0.2, CS 4.8+/-0.1, P=0.02) and the HOMA score (NS 3.0+/-0.4, CS 1.5+/-0.2, P=0.001) were significantly higher in NS. These differences persisted after adjusting for waist circumference. Of the inflammatory markers, only fibrinogen (P<0.01) and IL-6 (P=0.01) were significantly increased in NS. Despite significantly lower plasma NEFAs in NS, the NEFA:albumin ratio showed a non-significant trend to higher levels in NS (NS 10.7+/-0.1 micro mol/g, CS 8.7+/-0.1 micro mol/g, P=0.06). Within the NS group, multivariate backward regression analysis showed that NEFAs (P<0.01) and low-density lipoprotein (LDL) cholesterol (P=0.05) were significant negative independent predictors of FMD.


CONCLUSIONS
Endothelial function in NS is inversely correlated with plasma concentrations of NEFAs and LDL cholesterol. Dyslipoproteinaemia and NEFAs probably contribute to the increased risk of CVD seen in NS. We also postulate that in NS, hypoalbuminaemia increases the delivery of NEFAs to endothelial cells thereby impairing the synthesis and release of nitric oxide.
Dogra
Gursharan K
GK
Department of Medicine and Western Australian Heart Research Institute, University of Western Australia, Perth, Western Australia, Australia. sdogra@cyllene.uwa.edu.au
Herrmann
Susan
S
Irish
Ashley B
AB
Thomas
Mark A B
MA
Watts
Gerald F
GF
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001916:Brachial Artery / Q000503:physiopathology; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006706:Homeostasis; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology*; D007249:Inflammation / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications* / Q000503:physiopathology*; D012039:Regional Blood Flow; D012709:Serum Albumin / Q000032:analysis; D014664:Vasodilation
D001786:Blood Glucose; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012709:Serum Albumin