Suk-Hee Yu

Advanced glycation end products induce apoptosis and procoagulant activity in cultured human umbilical vein endothelial cells

Hyperglycemia and the late products of non-enzymatic glycosylation, called advanced glycation end products (AGEs), play an important role in the development of microvascular complications in diabetes mellitus. Previous studies have reported that a high glucose environment triggered apoptotic changes in human umbilical vein endothelial cells (HUVECs). Therefore, we investigated whether AGEs contribute to the development of apoptosis and prothrombotic activity in HUVECs. After incubation of HUVECs with 0.2, 2.2, 22, 220 and 2200 nM of AGE-bovine serum albumin (BSA) from 6 to 48 h, we assayed the degree of apoptosis and procoagulant activity (PCA). There were no significant differences between HUVECs cultured for 48 h with 0.2, 2.2 or 22 nM of AGE-BSA and in controls in the proportion of apoptotic cells (3.5 +/- 0.8%, 3.9 +/- 1.5% and 5.2 +/- 1.1% vs. 2.5 +/- 0.6%). However, the proportion of apoptotic cells increased significantly to 36.7 +/- 9.8% in 220 nM of AGE-BSA, and 72.3 +/- 10.2% in 2200 nM of AGE-BSA (P < 0.001). PCA levels were 142 +/- 10 s after 6 h of exposure to 22 nM (P < 0.01), 131 +/- 5 s after 6 h of exposure to 220 nM (P < 0.001), and 106 +/- 4 s after 6 h of exposure to 2200 nM of AGE-BSA (P < 0.001). These values show that PCA was shortened significantly from the basal value of 161 +/- 6 s, and remained below the basal level until the end of the study. The amount of tissue factor was also significantly increased in 22 and 220 nM of AGE-BSA compared to the controls. In conclusion, this study showed that AGEs could induce apoptosis and increase procoagulant activity in cultured HUVECs. We suggest that AGEs can contribute to the development of microvascular complications through cell death of HUVECs and functional changes of the blood vessels.

Malignant Hypertension : Aetiology and Outcome in 83 Patients

To evaluate the current pattern of aetiology and outcome in malignant hypertension, we reviewed all medical records of patients presenting between 1979 and 1985 who fulfilled WHO criteria for malignant hypertension. There were 83 patients, 43 males (52%) and 40 females (48%). Primary malignant hypertension was diagnosed in 17 cases (20%) and secondary lesions in 66 cases (80%). Overall one year survival was 94%, and 5 year survival 75%, which is similar to recent reports. Initial serum creatinine was a prognostic indicator.

Assessment of Fluid Shifts of Body Compartments using Both Bioimpedance Analysis and Blood Volume Monitoring

Fluid shifts are commonplace in chronic hemodialysis patients during the intra- and interdialytic periods. In this study, we evaluated fluid shifts of body compartments using both bioimpedance spectroscopy and blood volume monitoring from the start to the end of hemodialysis. 24 stable hemodialysis patients were included on the study. Relative change of blood volume was progressively reduced from the start to the end of hemodialysis (1 hr, -7.22±3.23%; 2 hr, -9.78±4.69%; 3 hr, -12.88±5.65%; 4 hr, -15.41±6.54%, respectively). Mean % reduction of intracellular fluid was not significantly different to that of extracellular fluid at the end of hemodialysis (Δ ICF, -6.58±5.34% vs. Δ ECF, -7.07±5.12%). Mean % fluid reduction of arms, legs and trunk was -11.98±6.76%, -6.43±4.37% and -7.47±4.56%, respectively at the end of hemodialysis. There were 3 characteristic patterns in blood-volume change. Similar amounts of fluid were removed from the extracellular and intracellular compartments during hemodialysis, with the arms showing the greatest loss in terms of body segments. The pattern of blood volume change measured by blood volume monitoring may be useful for more accurate determination of dry-weight and for correcting volume status in hemodialysis patients.

Serum globotriaosylceramide assay as a screening test for fabry disease in patients with ESRD on maintenance dialysis in Korea.

Background/Aims Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. Methods A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. Results Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. Conclusions Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.

IGF-1 is an Independent Risk Factor for Anemia in Diabetic Pre-dialysis Patients

Background We investigated whether the presence of diabetes mellitus (DM) was related to the degree of the anemia in predialytic patients with renal failure and what was the most relevant factor for anemia in patients with chronic kidney disease (CKD) from DM (DM-CKD). Methods Seventy seven patients (47 predialytic patients with long-term type 2 DM (DM-CKD) and 30 predialytic patients whose disease was due to other causes (non DM-CKD)) were enrolled in this study. The blood hemoglobin (Hb) and hematocrit, and the creatinine, ferritin, vitamin B12, folate, iron, LDH, albumin, hs-CRP, intact-PTH, erythropoietin, leptin and Insulin-like growth factor I (IGF-1) levels were measured using standard methods. The estimated GFR was calculated using the abbreviated MDRD equation. Results The two groups did not significantly differ as to age, gender, the serum creatinine level and the inflammatory status. The Hb level was significantly lower in the DM-CKD patients than that in the non DM-CKD patients (8.5±1.7 g/dL vs 9.6±1.6 g/dL, respectively, p=0.01). The Hb level was significantly lower in the DM-CKD patients who were being treated with ACE inhibitors (the DM-ACE patients) than that in the non DM-CKD patients who were being treated with ACE inhibitors (the non DM-ACE patients) (8.5±1.5 g/dL vs 10.8±1.6 g/dL, respectively, p=0.001). Multiple regression analysis indicated that serum IGF-1 concentration was independently associated with the Hb level (β=0.425, p=0.02) in the DM-CKD patients. Conclusions The Hb concentration was significantly lower in the DM-CKD patients than that in the non DM-CKD patients. It was independently associated with the serum IGF-1 concentration in the DM-CKD patients.

Association of serum albumin and homocysteine levels and cardio-ankle vascular index in patients with continuous ambulatory peritoneal dialysis

Background The cardio-ankle vascular index (CAVI) is a newly developed arteriosclerotic measurement that has been proposed as an alternative to aortic pulse-wave velocity (PWV). The present study used the CAVI to identify the main factors associated with arteriosclerosis in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods Fifteen CAPD patients were enrolled in the study. The CAVI is independent of the pressure and vascular reflection between the heart valve and the ankle. Serum albumin, uric acid, total calcium, phosphorus, lipid levels, high-sensitivity C-reactive protein and homocysteine concentrations in CAPD patients were measured using standard methods. Total body fat mass, truncal and non-truncal fat mass and lean body mass were measured using dual energy X-ray absorptiometry with a Lunar DPX-L scanner. Results CAPD patients had a mean CAVI of 9.37±3.16 m/sec, which was higher than the general population. The CAVI was negatively correlated with the serum albumin concentration (r=-0.548; p=0.034). Stepwise regression analysis showed that both the serum albumin concentration (β=-0.643, p=0.013) and the serum homocysteine level (β=0.486, p=0.004) were independently associated with the CAVI. Conclusions An increase in CAVI was independently associated with both serum albumin and homocysteine level.

Metabolic syndrome and chronic kidney disease as risk factors of osteoporosis.

AIMS Osteoporosis is a significant cause of morbidity and mortality, and is often accompanied by metabolic syndrome (MetS) and chronic kidney disease (CKD). We demonstrated the relationship among MetS, CKD and osteoporosis, and investigated the roles of MetS and CKD in the occurrence of osteoporosis in a healthy Korean population. METHODS The estimated glomerular filtration rate (eGFR) was calculated using the modification of diet in renal disease study equation. The diagnosis of MetS was made according to the updated guidelines from the American Heart Association/ National Heart, Lung, and Blood Institute. Bone mineral density (BMD) values were measured. A decreased BMD level was defined as either osteopenia or osteoporosis. RESULTS The subjects comprised 38.9% men and 61.1% women; 6.6% had CKD, 19.4% had MetS, and 12.2% had osteoporosis. In females, the prevalence of MetS and CKD was higher in those with decreased BMD (p = 0.034 and p = 0.114, respectively). The risks for decreased BMD increased with fewer MetS components and lower eGFR in a simple logistic analysis. However, the correlation disappeared when adjusted for age. In males, the prevalence of MetS and CKD was lower in decreased BMD (p = 0.034 and p = 0.157, respectively). Both the presence of MetS components and lower eGFR had protective effects on BMD values in simple and multiple logistic analyses. CONCLUSIONS In females, decreased BMD was positively related with both MetS and CKD. But, this relationship was not seen by adjustment for age. In males, lower BMD was negatively related to both MetS and CKD in unadjusted and adjusted models.