ABSTRACT
The objectives of this study were to determine the association between angiotensin converting enzyme (ACE) gene polymorphism and left ventricular (LV) geometry, and to clarify independent effects of ACE genotype on mortality after commencing dialysis in diabetic patients with end-stage renal disease (ESRD). A total of 106 diabetic patients, 71 men and 35 women, 11 type 1 and 95 type 2 diabetic, 57 +/- 12 (mean +/- standard deviation (S.D.)) years of age, who started dialysis were studied. Patients with cardiac diseases and those treated with ACE inhibitors were excluded because of potential effects on LV performance. Echocardiographic examination was performed within +/-2 months of the start of dialysis. Relation between ACE genotype and LV mass index (LVMI) or relative wall thickness (RWT) at onset of dialysis, and impact of ACE genotype on survival after commencing dialysis were evaluated. There were no significant differences in LVMI or RWT in the three ACE genotype groups at onset of dialysis. However, mortality of patients with the ACE-DD genotype was significantly higher than patients with the DI and II genotypes (hazard ratio, 2.318; P=0.043), based on a survival analysis with a mean follow-up duration of 60 months. The higher mortality in patients with the DD genotype was confirmed to be independent of LV hypertrophy and increases in RWT. In diabetic patients with ESRD, ACE genotype has no association with LV mass or RWT at the start of dialysis, but does have an independent impact on patient survival thereafter.
Subject(s)
Diabetic Nephropathies/genetics , Kidney Failure, Chronic/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic/genetics , Ventricular Dysfunction, Left/epidemiology , Ventricular Function, Left/physiology , Creatinine/blood , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/mortality , Diabetic Nephropathies/blood , Diabetic Nephropathies/enzymology , Diabetic Nephropathies/mortality , Echocardiography , Female , Genotype , Hematocrit , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/enzymology , Kidney Failure, Chronic/mortality , Male , Middle Aged , Sex Characteristics , Survival AnalysisABSTRACT
To investigate the association of oxidized low-density lipoprotein (ox-LDL) with the development of diabetic nephropathy, plasma levels of ox-LDL were measured in 70 patients with type 2 diabetes mellitus. A sandwich enzyme-linked immunoadsorbent assay (ELISA) using the mouse monoclonal antibody FOH1a/DLH3, which specifically recognizes oxidized phosphatidylcholine, and a horseradish peroxidase (HRP)-labeled goat anti-human apolipoprotein B IgG was used to measure ox-LDL levels. The mean age of the patients was 57.0+/-1 3.4 years, and the mean duration of diabetes was 13.4+/-8.5 years. Plasma ox-LDL levels were similar in patients with normoalbuminuria (13.7+/-3.9 U/ml), patients with microalbuminuria (12.8+/-3.9 U/ml), and normal controls (12.5+/-4.2 U/ml). However, the plasma ox-LDL level in patients with macroalbuminuria (16.8+/-7.5 U/ml) was significantly higher than those in the other groups (P<0.05). Hemoglobin A1c (HbA1c) levels were similar in diabetic patients with normoalbuminuria (8.2+/-2.2%), microalbuminuria (7.8+/-1.3%), or macroalbuminuria (7.2+/-1.4%). There was no significant correlation between the ox-LDL level and the HbA1c level. The significantly elevated plasma ox-LDL levels in patients with macroalbuminuria suggest that ox-LDL may play an important role in the progression of diabetic nephropathy.
