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.

Chronic asymptomatic pyuria precedes overt urinary tract infection and deterioration of renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. METHODS: We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. RESULTS: With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). CONCLUSIONS: Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.

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.

The investigation of macrophage infiltration in the early phase of ischemic acute renal failure in mice.

BACKGROUND/AIMS: Inflammation plays a key role in ischemic acute renal failure (ARF). The present study investigated the infiltration of macrophages in the early phase of ischemic ARF in mice. METHODS: Ischemic ARF was induced by renal clamping for 22 min, while the control mice underwent sham surgery (no clamping). The serum creatinine and blood urea nitrogen (BUN) levels were measured in the control and post-ischemia mice. Immunofluorescence staining was used to measure the number of CD 11b-positive cells in the kidney tissue sections to determine the amount of post-ischemic macrophage infiltration. Lipo-Cl2MBP (clodronate) for macrophages depletion was injected via a tail vein 5 d before ischemia induction and again 2 d before ischemia induction. RESULTS: The study found that the post-ischemia mice had higher levels of serum creatinine and BUN at 16 and 24 h compared to the controls. Immunofluorescence staining showed there were more macrophages in the post-ischemic tissue at 2, 8, 16 and 24 h compared to the control tissue, and that most of these macrophages were located in the outer medulla. The mice treated with clodronate prior to ischemia induction were found to have lower levels of serum creatinine compared to those mice that weren't treated with clodronate. CONCLUSIONS: There was significant infiltration of macrophages from the early phase of ischemic ARF, and this peaked at 16-24 h. Macrophage depletion using clodronate was protective against ischemic ARF.

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 (beta=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 (beta=-0.643, p=0.013) and the serum homocysteine level (beta=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.

Association between serum n-terminal pro-brain natriuretic peptide concentration and left ventricular dysfunction and extracellular water in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: This study investigated the association between serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and extracellular water (ECW%) and left ventricular (LV) dysfunction in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: The study involved 30 stable CAPD patients: 14 males, 16 females; mean age 52 +/- 14 years; mean CAPD duration 34 +/- 12 months; 12 with diabetes mellitus (DM) and 18 non-DM. Serum NT-pro-BNP levels were determined using electrochemiluminescence immunoassay. Baseline echocardiography was performed using a Hewlett-Packard Sonos 1000 (Andover, Massachusetts, USA) device equipped with a 2.25-MHz probe, allowing M-mode, two-dimensional, and pulsed Doppler measurements. Left ventricular mass index (LVMI) was calculated according to the Penn formula. A multifrequency bioimpedance analyzer was used; ECW% was calculated as a percentage of total body water and was considered the index of volume load. RESULTS: (1) Serum NT-pro-BNP level, ECW%, LVMI, and LV ejection fraction in CAPD patients were 3924 (240 - 74460) pg/mL, 36.7% +/- 2.2%, 158 +/- 48 g/m2, and 60.5% +/-11.2%, respectively. (2) Patients were divided into three tertiles (10 patients each) according to their serum NT-proBNP concentration [1st tertile 1168 (240 - 2096), 2nd tertile 4856 (2295 - 20088), 3rd tertile 35012 (20539 -74460) pg/mL]. The tertiles did not differ significantly in terms of age, sex, presence of DM, body mass index, or PD duration. Patients in the 3rd tertile (highest serum NT-proBNP concentration) had the highest LVMI (126 +/- 45 vs 160 +/-41 vs 200 +/- 23 g/m2 for 1st, 2nd, 3rd tertiles, respectively) and the lowest LV ejection fraction (66% +/- 11% vs 62% +/-6% vs 55% +/- 9%). ECW% did not differ significantly between tertiles (35.5% +/- 2.0% vs 37.5% +/- 2.0% vs 36.5% +/-2.0%). (3) In CAPD patients, serum NT-pro-BNP levels correlated positively with LVMI (r = 0.628, p = 0.003) and negatively with LV ejection fraction (r = -0.479, p = 0.033). Serum NT-pro-BNP levels did not correlate with ECW% (r = 0.227, p = 0.25). (4) Stepwise regression analysis showed that LV ejection fraction (beta = -0.610, p = 0.015) and LVMI (beta = 0.415, p = 0.007) were independently associated with the serum NT-pro-BNP concentration. CONCLUSIONS: There was no link between ECW% and serum NT-pro-BNP concentration. Thus, serum NT-pro-BNP levels may not provide objective information with respect to pure hydration status in CAPD patients. In contrast, serum NT-pro-BNP levels were linked to LVMI and LV ejection fraction in CAPD patients. Therefore, while the serum NT-proBNP concentration might not be a useful clinical marker for extracellular fluid volume load, it appears useful for evaluating LV hypertrophy and LV dysfunction in CAPD patients.

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 (delta ICF, -6.58+/-5.34% vs. delta 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.

Heat shock protein expression in adenosine triphosphate depleted renal epithelial cells.

BACKGROUND: In this study, the putative interactions between apoptosis and heat shock proteins disturbed as a result of ATP depletion were investigated as a hypoxia model. METHODS: The direct cellular damages were assessed by the release of LDH from the cytoplasm of the human tubular epithelial cells (HK-2 cells) following ATP depletion. The Bcl-2/Bax mRNA expression ratio, used as an index to assess to what extent apoptosis contributed to tubular cell damage, and the expressions of HSP 90, 72 and 27 in relation to the Bcl-2/Bax ratio in the ischemic model, as parameters of their functional contributions to tubule cell damage, were also studied. Heat preconditioning (HS) was performed at 43 degrees C in a temperature-regulated water bath for 1 h. RESULTS: The release of LDH due to ATP depletion was not significantly increased in HK-2 cells compared to the control, but was slightly increased in heat preconditioned cells compared to non heat preconditioned cells, but the difference was not statistically significant (6.33 +/- 0.57 U/L vs. 8.67 +/- 2.52 U/L, p>0.05). The Bcl-2/ Bax mRNA expression ratio increased progressively from the control to the heat preconditioned and ATP depleted cells (control; 100%, ATP depletion; 154 +/- 6%, heat preconditioning; 212 +/- 6%, heat preconditioning and ATP depletion; 421 +/- 8%). No contribution of heat preconditioning and ATP depletion was observed on the expressions of HSP90 and HSP27. However, HSP72 expression was prominent by ATP depletion, especially after heat preconditioning. CONCLUSION: There may be a possibility that the preservation of cytolytic damage and an increase in the Bcl-2/Bax mRNA expression ratio is related to the increase of HSP72 in ATP depletion as a hypoxia model.

The effects of low calcium dialysate on arterial compliance and vasoactive substances in patients with hemodialysis.

BACKGROUND: Considering that dialysate calcium concentration is potentially a main determinant of the serum ionized calcium level and vasoconstriction is associated with the blood calcium concentration, we conducted a study to evaluate the interdialytic effects of treatment with a low calcium dialysate (LdCa, 1.25 mmol/L) on the changes in arterial compliance (AC), blood pressure (BP), biochemical parameters and vasoactive substances. METHODS: Eight hemodialysis (HD) patients (mean age: 46.8 +/- 13.7 years, 4 men and 4 women) were included in the study. AC, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), serum ionized Ca, intact-PTH, serum nitric oxide and aldosterone were compared after 10 sessions of treatment with LdCa. Right carotid artery diameter was measured 3 times using a real time B-mode ultrasound imager (Hewlett-Packard Sonos 2000) and AC was calculated using the Hayoz method. RESULTS: 1) AC was recorded as 0.140 (0.080-0.170) mm2/kPa at the baseline (1.75 mmol/L calcium dialysate), 0.170 (0.050-0.290) mm2/kPa after LdCa treatment (p < 0.05 versus baseline), and 0.140 (0.070-0.250) mm2/kPa following the HdCa treatment (p < 0.05 versus LdCa data). 2) MAP and PP were calculated at 114.12 +/- 10.56 mmHg and 63.50 +/- 10.87 mmHg at the baseline; 98.37 +/- 15.14 mmHg and 56.50 +/- 5.95 mmHg after LdCa treatment (p < 0.05 versus baseline); and 115.75 +/- 9.64 mmHg and 62.00 +/- 15.71 mmHg following HdCa treatment (p < 0.05 versus LdCa data). 3) Serum ionized Ca and intact-PTH were measured at 4.66 +/- 0.40 mg/dL and 25.08 +/- 16.44 pg/mL at the baseline; 4.45 +/- 0.28 mg/dL and 90.71 +/- 27.03 pg/mL after LdCa treatment (p < 0.05 versus baseline); and 4.65 0.43 mg/dL and 24.08 +/- 15.44 pg/mL following HdCa treatment (p < 0.05 versus LdCa data). 4) Serum aldosterone concentration was 300.8 (65.5-836.1) pg/mL at the baseline, and 220.2 (42.8-527.9) pg/mL after LdCa treatment (p < 0.05). CONCLUSION: There were favorable changes in AC, BP, biochemical parameters after treatment with LdCa. These changes may be associated with the reduction in serum ionized calcium and decreased serum aldosterone concentration.