Abstract
It is well known that patients with diabetes have a high incidence of cardiovascular disease (CVD), and the incidence of CVD becomes substantially elevated with development of diabetic nephropathy. The mechanisms for dyslipidemia in diabetic nephropathy are multifactorial and complex. Long-term hyperglycemia causes generalized vascular endothelial damage, which reduces functional lipoprotein lipase, leading to increased triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C). In overt-diabetic nephropathy, hypoproteinemia markedly increases low-density lipoprotein cholesterol (LDL-C), and renal failure specifically increases remnant lipoproteins and decreases HDL-C and LDL-C. Overt diabetic nephropathy exhibits remarkable postprandial hypertriglyceridemia with hyper-apolipoprotein (apo) B48, a marker of chylomicron and its remnants. Apo CIII is a key inhibitor of lipolysis and particle uptake of TG-rich lipoproteins, which is specifically increased in advanced chronic kidney disease, irrespective of the presence of diabetes. LDL size becomes smaller with advanced stages of diabetic nephropathy, whereas LDL size is not reduced in hemodialysis patients (HD). HD patients have marked lower levels of HDL3-C than controls. HD patients also have substantially low apo AI and high serum amyloid A (SAA) levels, suggesting the replacement of apo AI by SAA is stimulated in HDL particles.
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Hirano T, Oi K, Sakai S, et al. High prevalence of small dense LDL in diabetic nephropathy is not directly associated with kidney damage: a possible role of postprandial lipemia. Atherosclerosis. 1998;141:77–85.
Hayashi T, Hirano T, Taira T, et al. Remarkable increase of apolipoprotein B48 level in diabetic patients with end-stage renal disease. Atherosclerosis. 2008;197:154–8.
Hirano T, Ookubo K, Kashiwazaki K, et al. Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are specifically elevated in type 2 diabetic patients with nephropathy: comparison of primary renal disease. Clin Chim Acta. 2000;299:65–75.
Kashiwazaki K, Hirano T, Yoshino G, et al. Decreased release of lipoprotein lipase is associated with vascular endothelial damage in NIDDM patients with microalbuminuria. Diabetes Care. 1998;21:2016–20.
Hirano T, Sakaue T, Misaki A, et al. Very low-density lipoprotein-apoprotein CI is increased in diabetic nephropathy: comparison with apoprotein CIII. Kidney Int. 2003;63:2171–7.
Hirano T, Hayashi T, Adachi M, et al. Marked decrease of apolipoprotein A-V in both diabetic and nondiabetic patients with end-stage renal disease. Metabolism. 2007;56:462–3.
Hirano T, Furukawa S, Kurokawa M, Ebara T, Dixon JL, Nagano S. Intracellular apoprotein B degradation is suppressed by decreased albumin concentration in Hep G2 cells. Kidney Int. 1995;47:421–31.
Hirano T, Naito H, Kurokawa M, et al. High prevalence of small LDL particles in non-insulin-dependent diabetic patients with nephropathy. Atherosclerosis. 1996;123:57–72.
Hirano T, Nohtomi K, Nakanishi N, et al. Ezetimibe decreases serum amyloid A levels in HDL3 in hemodialysis patients. Clin Nephrol. 2010;74:282–7.
Honda H, Ueda M, Kojima S, et al. Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients. Atherosclerosis. 2012;220(2):493–501.
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Hirano, T. Abnormal lipoprotein metabolism in diabetic nephropathy. Clin Exp Nephrol 18, 206–209 (2014). https://doi.org/10.1007/s10157-013-0880-y
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DOI: https://doi.org/10.1007/s10157-013-0880-y