Patients on maintenance hemodialysis (HD) are atBackground. Apolipoprotein (apo) E polymorphism conincreased risk for atherosclerotic vascular disease, and sists of three major isoproteins (E2, E3, and E4). Because of cardiovascular disease is the major cause of mortality in their difference in a lipid-modulating effect, the polymorphism this setting [4]. Uremic dyslipidemia has been proposed has been reported to affect the morbidity of atherosclerosis in as a primary cause for this increased prevalence of athgeneral population. Therefore, in hemodialysis (HD) patients, the apo E polymorphism may also modulate serum levels of erosclerotic complications [5, 6].cholesterol and susceptibility to atherosclerotic vascular dis-However, little has been known about the influence ease. of apo E polymorphism on uremic dyslipidemia in HD Methods. We determined apo E phenotypes in 493 HD papatients. Moreover, whether apo E polymorphism has tients and 422 controls. We also investigated vascular risk proan influence on the prevalence of atherosclerotic complifile and measured postprandial serum levels of lipids and apos in the dialysis patients.cations in dialysis patients remains to be clarified.Results. We found a similar phenotype distribution and allele frequency between HD patients and healthy controls. Serum levels of total cholesterol, triglyceride, and apo A I, A II, METHODSand C III did not differ significantly among patients withWe studied the prevalence of vascular disease and the phenotypes apo E2/3, E3/3, and E3/4. Patients with apo E3/4 had significantly lower levels of high-density lipoprotein choles-vascular risk profile, including the apo E phenotype, in terol, significantly higher levels of low-density lipoprotein cho-
The TT genotype of HL mutation may serve as a protective factor against vascular disease by increasing HDL cholesterol levels in hemodialysis patients with higher CETP levels.
Background Chronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear. Methods We housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia. Results Levels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-β1 (TGF-β1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-β1 was significantly enhanced in the hypoxic mice. Conclusions These results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN.
A common mutation of cholesteryl ester transfer protein genein hemodialysis patients [2, 3] and is related to an occurin dialysis patients. rence of ischemic heart disease in hemodialysis patientsBackground. In patients on maintenance hemodialysis, a[4] as well as in the general population. decreased concentration of high-density lipoprotein choles-Recently, a common missense mutation, D442G (Asp terol (HDL-C) is an apparent independent risk factor for vascu-442 to Gly), in exon 15 of the cholesteryl ester transfer lar disease (VD). A common missense mutation of cholesteryl ester transfer protein (CETP) gene, D442G (Asp442 to Gly), protein (CETP) gene has been reported in the Japanese increases HDL-C levels, but the mutation may also diminish general population [5]. CETP mediates the transfer of the activity of reverse cholesterol transport. cholesteryl esters (CEs) from HDL into triglyceride-rich Methods. We compared the genotype distribution of the lipoproteins and thereby stimulates reverse cholesterol D442G polymorphism and postprandial serum lipid levels between patients with and without VD in 414 hemodialysis patransport [6, 7]. The D442G mutation results in markedly tients. increased HDL-C levels [5], whereas the mutation may Results. Serum levels of total cholesterol and HDL-C did reduce activity of reverse cholesterol transport [7].not differ in patients with the mutation [group M (ϩ)] and Whether this mutation affects atherosclerotic complicawithout the mutation [group M (Ϫ)] and in patients with and tions in dialysis patients with uremic dyslipidemia rewithout VD. However, patients with below median HDL-C levels (Ͻ45 mg/dl) had a significantly higher prevalence of VD mains to be clarified. than those with above median HDL levels (26.0 vs. 15.2%, P Ͻ 0.01). Moreover, in this low-HDL-C subgroup, group M (ϩ) patients had a significantly higher prevalence of VD
These suggest that a smaller LDL size, which is associated with higher levels of TG and CETP and the HL/CC genotype, may serve as a risk factor for CAD in HD patients.
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