Nephrology Dialysis Transplantation, Vol 13, Issue 5 1183-1188, Copyright © 1998 by Oxford University Press
C Deighan, M Caslake, M McConnell, J Boulton-Jones and C Packard
Background: Heavy proteinuria is associated with
marked abnormalities of lipoprotein metabolism and increased risk of
atherogenesis. It is possible that qualitative as well as quantitative
changes occur in lipoproteins to contribute to increased cardiovascular
risk; for example, it is known that LDL exhibits heterogeneity, with small,
dense LDL III particles being more atherogenic.
Methods: We investigated LDL subfractions (measured by
density gradient ultracentrifugation), VLDL subfractions, and post-heparin
lipases in 12 patients with primary glomerular disease and 24-h albuminuria
>2.5 g. These were compared to 23 age- and sex-matched controls.
Results: Total LDL concentrations were similar in
proteinuric patients and controls; however, there was a shift in
subfraction distribution. The larger LDL I and LDL II particles were lower
in the proteinuric group (29±24 vs
62±26 mg/dl P=0.011 and 121±80
vs 197±74 mg/dl P=0.028), whereas the
concentration of atherogenic LDL III (small dense) was higher
(135±64 vs 75±71 mg/dl
P=0.0016). The concentration of total VLDL and both its subfractions were
increased in the patients with proteinuria. Post-heparin hepatic and
lipoprotein lipase levels were similar to normal.
Conclusions: These findings suggest that the
atherogenicity of LDL is increased in patients with heavy proteinuria
because of the redistribution towards smaller denser particles. Since
small, dense LDL has a lower affinity for the LDL receptor, the altered
nature of the lipoprotein in proteinuria may decrease its clearance by the
receptor-mediated pathway and contribute to the reduced clearance of LDL
observed in this population. This may contribute to progression of renal
failure or the accelerated vascular disease found in patients with heavy
proteinuria. Key words: cardiovascular risk;
glomerulonephritis; LDL subfractions; lipoprotein metabolism; low-density
lipoprotein; proteinuria
ORIGINAL ARTICLES
Increased atherogenicity of low-density lipoprotein in heavy proteinuria
Renal Unit and Department of Pathological Biochemistry, Glasgow Royal Infirmary University NHS Trust, Castle Street, Glasgow G4 0SF, UK; Corresponding author
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  C. J. DEIGHAN, M. J. CASLAKE, M. MCCONNELL, J. M. BOULTON-JONES, and C. J. PACKARD Comparative Effects of Cerivastatin and Fenofibrate on the Atherogenic Lipoprotein Phenotype in Proteinuric Renal Disease J. Am. Soc. Nephrol., February 1, 2001; 12(2): 341 - 348. [Abstract] [Full Text]
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