[Evaluation of Payne's formula for the correction of calcium: comparison with improved calcium and albumin measurement methods].

The ionized or free fraction of serum calcium is physiologically important for cellular function, but we most often measure total serum calcium. There are a number of correction formulas that can be used to estimate whether low total serum calcium can be attributed simply to low albumin or serum protein. In Japan, Payne's formula has been widely used to correct calcium concentration. However, there are some problems in the measurement methods of total calcium and serum albumin which were used to establish Payne's formula with respect to specificity, calibration curve and stability. Recently, improved measurement methods of calcium and albumin have been adopted at clinical laboratories. Here we evaluated Payne's formula by comparing it with improved measurement methods of total calcium and serum albumin. For the total calcium measurement, o-CPC (o-cresolphthaleincomplexone), CPZ(chlorophosphonazo) III, and enzymatic methods were used. For the serum albumin measurement, BCG (bromocresol green) and improved BCP(bromocresol purple) methods were used. The results of this comparison study suggest that the calcium correction equation is not affected by changes in total calcium concentration, but the assay used for albumin may affect the calcium correction equation. Using multiple linear regression, the following equations were derived: BCG between CPZ III [corrected Ca(mg/dL) = total Ca-0.76ALB + 3.2], and improved BCP between CPZ III [corrected Ca = total Ca-0.7ALB + 2.6]. These formulas are simplified respectively as [corrected Ca = total Ca + 0.8(4-ALB], and [corrected Ca = total Ca + 0.7 (4-ALB)]. We conclude that Payne's formula is valid with the BCG method, but with the improved BCP method, our formula is more suitable for correcting calcium.

Additional reduction in serum phosphorus levels by pulverized lanthanum carbonate chewable in hemodialysis patients.

Lanthanum carbonate (LC) is one of the relatively new phosphate binders. The general LC dosage form is a chewable pharmaceutical preparation. This investigation was targeted to subjects who do not chew LC chewable preparations adequately, for the purpose of studying the clinical efficacy of changing to pulverized prescriptions, such as changes in serum phosphorus levels (P levels). The study took place at Minamisenju Hospital in October 2011, with 41 subjects on maintenance hemodialysis. We pulverized all of the LC chewable medicines of the LC insufficient mastication group (non-chewing: NC group, n = 18) using a crusher, and changed them to pulverized prescriptions. The testing period was set at 10 weeks. In the NC group, there was a significant lowering of P levels from 5.86 ± 1.31 mg/dL before pulverization of the LC chewable preparation (week 0) to 5.38 ± 1.26 mg/dL after 2 weeks of administration of the pulverized medication (P = 0.0310), 5.20 ± 1.25 mg/dL after 4 weeks (P = 0.0077), and 5.12 ± 1.34 mg/dL after 6 weeks (P = 0.0167). P levels in other patients than NC group showed no significant change. In this study, the P levels in the NC group was lowered significantly by changing the LC chewable to the pulverized prescription, and the residual LC images on the abdominal X-rays disappeared to the point where they could barely be confirmed.

Left atrial volume is an independent predictor of all-cause mortality in chronic hemodialysis patients.

OBJECTIVE: An enlarged left atrium (LA) has recently been identified as a risk factor for adverse cardiovascular outcomes in various pathologic conditions. However, few studies have evaluated its prognostic value in hemodialysis (HD) patients. METHODS: We conducted an observational study to investigate whether an enlarged LA predicted all-cause mortality in 174 HD patients. Patients were stratified into two groups based on the LA volume index (LAVI) value of 32 mL/m2. RESULTS: An increased left atrial volume index (LAVI >32 mL/m(2)) was present in 28 (16.1%) of the HD patients. During the follow-up period (50.1 ± 22.4 months), 77 patients (44.3%) died. A Kaplan-Meier analysis revealed that the 7-year survival rate was significantly lower in the group whose LAVI was >32 mL/m(2) than in the group whose LAVI was ≤ 32 mL/m(2) (p=0.0033). Multivariate analyses adjusted for echocardiographic parameters and clinical and laboratory data showed that increased LAVI was an independent predictor of all-cause mortality (hazard ratio 1.030, 95% confidence interval 1.004-1.056, p=0.0260). Moreover, increased LAVI had a higher predictive value for all-cause mortality (area under the receiver operating characteristic curve=0.612, p=0.0059) among the measured echocardiographic parameters. CONCLUSION: The results of the present study suggested that measurement of LAVI may be helpful in the risk stratification of HD patients and in providing therapeutic direction for their management.

Effect of the antiplatelet agent cilostazol on endovascular inflammatory biochemical parameters and the clinical symptoms of peripheral artery disease and restless legs syndrome in hemodialysis patients.

BACKGROUND: Peripheral artery disease (PAD) is a common complication in patients receiving hemodialysis (HD). Cilostazol is used for the treatment of ischemic symptoms in patients with PAD, based on its antiplatelet and vasodilating effects. In addition to these beneficial effects on clinical symptoms in PAD patients, cilostazol has been proposed to have additional effects on clinical symptoms in patients with restless legs syndrome (RLS) via the upregulation of dopamine. We performed an observational, prospective study to evaluate the effect of cilostazol on several clinical and biochemical parameters in HD patients with PAD and RLS. METHODS: All the study patients received cilostazol treatment for 12 months. During the study period, several biochemical parameters, such as high-sensitivity CRP, von Willebrand antigen (VW-Ag), triglyceride (TG), high-density lipoprotein (HDL) and malondialdehyde-modified low-density lipoprotein, were monitored. A questionnaire on the physical status of PAD and RLS was also completed. 45 HD patients who received cilostazol were compared with a control group of 22 patients. RESULTS: The patients who continued cilostazol treatment exhibited a improvement in their serum inflammatory and biochemical parameters (VW-Ag, TG, HDL). Although PAD and RLS scores were not improved by multivariate analysis, several patients showed improvement of signs and symptoms which were included in the PAD or RLS scores. CONCLUSION: The treatment of HD patients with cilostazol improved some of the lipid-related and endovascular inflammatory biochemical parameters associated with PAD, and relieved the clinical symptoms and physical status of PAD in some cases.

Cardiovascular autonomic neuropathy studied by a laser-Doppler blood flowmeter in hemodialysis patients.

OBJECTIVE: Orthostatic hypotension during a hemodialysis (HD) session affects not only the modality but daily quality of life for HD patients because many of them have combined dysfunction of both sympathetic and parasympathetic nervous systems. Although various non-invasive methods have been applied for the evaluation of autonomic function, no monitor has been devised for measuring the dysfunction during blood purification therapy. PATIENTS AND METHODS: We evaluated the usefulness of laser-Doppler blood flowmeter (LDF) for measuring autonomic function of stable 34 regular HD patients and 24 healthy controls. The LDF device was applied for autonomic test by measuring periflux blood flow decreasing velocity (PDV) accompanied with Valsalva maneuver. We also evaluated the correlation between PDV and conventional tests for atherosclerosis. RESULTS: The average PDV (3.79±1.77) in HD population level was significantly lower than that of healthy controls (8.72±6.00). We also found a significant correlation between PDV and conventional methods such as heart rate variability and ankle-brachial blood pressure index. CONCLUSION: Measurement of PDV by LDF is as useful as a conventional method for evaluating autonomic function in HD patients. The convenience of the device offers the benefit of daily and frequent measurement of autonomic dysfunction.

Analysis of plasma adipocytokines related to clinical and laboratory data in the maintenance hemodialysis patients.

BACKGROUND: Atherosclerotic vascular diseases such as cerebrovascular and cardiovascular diseases are major causes for fatality of hemodialysis (HD) patients. Since adipocytokines are key players for arteriosclerosis in the concept of metabolic syndrome (MetS), we aimed to determine whether circulating levels of major three adipocytokines, adiponectin, TNF-alpha, and leptin, could be associated with various parameters and clinical events in HD patients who are diagnosed as MetS using a new criteria designed for the Japanese population. PATIENTS AND METHODS: We enrolled 53 very stable patients under maintenance HD at Minami-Senju Hospital. Basically, clinical and laboratory data were taken just before HD therapy. HD sessions were performed regularly and all the participants took oral administration and injection as usual. A cross-sectional study was performed to evaluate clinical and laboratory data related to three major adipocytokines, adiponectin, TNF-alpha and leptin. RESULTS: We observed no significant differences of three adipocytokines when the participants were divided in accordance with existence of MetS or past cerebrocascular/cardiovascular diseases. Only the serum adiponectin levels were significantly different in two groups categorized by existence of diabetes mellitus. Serum triglycerides (TG) were significantly correlated with two circulating adipocytokines, adiponectin (r=-0.328, p<0.016) and leptin (r=0.397, p<0.003), when we analyzed all 53 patients together. CONCLUSION: Plasma adiponectin and leptin are expected as contributors related to dyslipidemia, suggesting these may be targets of prevention of vascular diseases in maintenance HD patients.

Effects of sevelamer on the progression of vascular calcification in patients on chronic haemodialysis.

BACKGROUND/AIM: Vascular calcification is thought to be associated with a high cardiovascular mortality rate in patients with end-stage renal disease. Control of hyperphosphataemia is important for the treatment of the vascular calcification. The aim of the present study was to evaluate the effects of sevelamer hydrochloride on the progression of aortic calcification in haemodialysis (HD) patients. METHODS: 42 HD patients were studied in this study and divided into two groups (sevelamer vs. calcium). Sevelamer was added and titrated up to achieve serum P control for 6 months. The estimations of aortic calcification index (ACI) by abdominal computed tomography scans were performed twice in each patient. We compared the changes in serum calcium, phosphorus, intact parathyroid hormone, and lipids in two groups. RESULTS: Serum phosphorus levels decreased significantly from 6.7 +/- 0.7 to 6.2 +/- 0.5 mg/dl with no changes in serum intact parathyroid hormone levels in the sevelamer group (p < 0.01), and increased from 6.5 +/- 1.0 to 6.7 +/- 1.1 mg/dl in the calcium group (p < 0.05). Serum calcium levels did not change in the sevelamer group and calcium group. The serum levels of total cholesterol decreased significantly from 158.5 +/- 20.7 to 146.2 +/- 24.1 mg/dl (p = 0.024) and the low-density lipoprotein cholesterol level from 65.3 +/- 14.4 to 54.7 +/- 11.6 mg/dl (p = 0.014) in the sevelamer group. Serum C-reactive protein decreased significantly from 0.14 +/- 0.13 to 0.08 +/- 0.11 mg/dl in the sevelamer group (p = 0.038) and significantly increased (0.18 +/- 0.09 vs. 0.22 +/- 0.12 mg/dl) in the calcium group (p = 0.042). The mean changes in ACI (DeltaACI) were 3.6 +/- 1.5% in the sevelamer group and 8.2 +/- 3.1% in the calcium group. CONCLUSIONS: Sevelamer allows a better serum phosphorus control compared with calcium-based phosphate binder and suppresses the progression of aortic calcification in HD patients.

Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients.

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that inhibits osteoclast differentiation and activity. OPG-deficient mice develop severe osteoporosis and medial arterial calcification. The expression of OPG is detected in early atherosclerotic lesions in non-uraemic patients. We examined whether serum OPG is associated with aortic calcification in haemodialysis patients. METHODS: Serum OPG was measured in 102 patients who were undergoing haemodialysis. The aortic calcification index (ACI) was assessed by computed tomography scans. RESULTS: Serum OPG level, measured by enzyme-linked immunosorbent assay, was significantly greater in patients with higher ACI than in those with lower ACI. There was a direct relationship between ACI and serum OPG levels and a positive association between OPG and ACI (r = 0.483, P<0.0001). Multiple regression analyses indicated that serum OPG levels were independently associated with the severity of aortic calcification (P<0.0001). CONCLUSIONS: These findings show that serum OPG levels are associated with the extent of vascular calcification, suggesting that OPG may be involved in the development of vascular calcification in haemodialysis patients.

Left ventricular hypertrophy is associated with arterial stiffness and vascular calcification in hemodialysis patients.

Left ventricular hypertrophy (LVH) is the most frequent cardiac abnormality in patients with end-stage renal disease (ESRD). Recent studies have shown that arterial stiffness is associated with mediacalcinosis in these patients. However, whether arterial stiffness and vascular calcification are associated with the LVH in patients with ESRD has not been well established. Forty-nine patients on chronic hemodialysis participated in this study. 1) To better understand the mechanism underlying the increased incidence of LVH, we studied the relation between LVH and each of arterial wall stiffness, aortic calcification, and numerous clinical parameters in 49 patients on chronic hemodialysis. 2) To evaluate the contribution of arterial stiffness and arterial calcification to LVH in hemodialysis patients, we performed the present clinical analysis on 49 patients on chronic hemodialysis. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The left ventricular mass index (LVMI) was estimated by M-mode echocardiography. To understand the mechanism underlying the increased incidence of LVH, we examined the factors contributing to LVMI in these patients. The correlation between each of the study parameters and LVMI as an indicator of LVH was then examined. The LVMI value was correlated positively with PWV (r=0.439, p=0.0014), systolic blood pressure (r=0.421, p=0.0023), and ACI (r=0.467, p=0.0006). A stepwise linear regression analysis showed that PWV, systolic blood pressure, and ACI were independently associated with LVH in our subjects. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients, with vascular calcification being the most important contributor to the development of LVH. Alteration of pulsatile dynamics contributes to an increase in left ventricular load and thus is also related to the LVH in these patients. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients. Vascular calcification, which alters the pulsatile dynamics and thereby contributes to an increase in left ventricular load, is the most important contributor to the development of LVH in patients undergoing hemodialysis.

The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis.

BACKGROUND: The aortic calcification index (ACI), estimated on abdominal computed tomographic scans, has been associated with the extent of arteriosclerosis in hemodialysis patients. However, the contribution of biochemical markers to the progression of vascular calcification in patients undergoing hemodialysis is not fully understood. METHODS: We examined the relationship between coronary risk factors; metabolic factors, including serum osteoprotegerin (OPG) concentration; and progression of vascular calcification in 26 dialysis patients. RESULTS: Mean patient age was 52.6 +/- 8.7 (SD) years, and mean duration of dialysis therapy was 7.7 +/- 5.8 years. ACI was measured twice in each patient, and the mean interscan period was 4.9 +/- 0.3 years. Mean ACI changed from 22.2 +/- 24.2 to 33.9 +/- 28.8 overall, and mean change in ACI (DeltaACI) was 12.0 +/- 9.9. Patients were divided into 2 groups: slow progressors, with DeltaACI of 4.1 +/- 3.2 (n = 13), and rapid progressors, with DeltaACI of 19.8 +/- 7.9 (n = 13). Serum fasting glucose and CRP levels of rapid progressors were high, and their serum albumin and intact parathyroid hormone levels were low. Multiple regression analyses showed that serum OPG levels were independently associated with vascular calcification in the hemodialysis patients studied. CONCLUSION: Rapid progression of vascular calcification was associated with dose of calcium carbonate prescribed and serum OPG concentration. The clinical significance of these observations remains to be determined.