Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial.

BACKGROUND: Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. METHODS: This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. RESULTS: Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0, p = .001). Dietary phosphorus intake was not related to cFGF23. CONCLUSIONS: Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.

Accuracy of a Nutrient Database in Estimating the Dietary Phosphorus-to-Protein Ratio and Using a Boiling Method in Low-Phosphate Hospital Diets.

The use of the dietary phosphorus-to-protein ratio (PPR) to reduce dietary phosphorus while maintaining protein intake is valuable for nutritional management in the dialysis population, but the actual PPR values in hospital meals have not been determined. We aimed to determine the accuracy of a nutrient database for estimating the PPR in low-phosphate hospital diets compared with the accuracy of chemical analysis and produce hospital diets with low-phosphate content by boiling meat for 30 minutes before cooking. The phosphorus and protein content of 26 cooked dishes selected from the hospital menu was estimated using a food composition table (FCT) and sent for chemical analysis. Comparisons of FCT-based estimated values with measured values for every 100 g of tested foods revealed an overestimation for the PPR both in plant-based dishes (mean difference ± SD, 4.1 ± 14.6 mg/g, P = 0.06), and in meats (2.1 ± 2.3 mg/g, P = 0.06). By boiling meats, we crafted diets with PPR as low as 8 mg/g. Caution should be exercised in estimating the PPR using a FCT in hospital diets and boiling should be used to prepare hospital meals. Such diets will be promoted for dialysis patients in both inpatient and outpatient settings.

Risk factors for severe hypocalcemia after parathyroidectomy in prevalent dialysis patients with secondary hyperparathyroidism.

PURPOSE: Hypocalcemia is one of the common complications after parathyroidectomy (PTX). Severe hypocalcemia (SH) can lead to tetany, cardiac arrhythmia and even sudden death. However, predictors for the development of SH in patients with secondary hyperparathyroidism demonstrated in some small-scale studies with a limited sample size remain inconclusive. METHODS: A retrospective chart review of 420 consecutive dialysis patients who underwent PTX during a 12-year period was performed. We checked serum levels of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) for three consecutive days postoperatively. SH was defined as the minimum values of serum calcium lower than 1.875 mmol/L (7.5 mg/dL) within 3 days after operation. RESULTS: The mean (±SD) age of our study population was 53 ± 12 years, and more than half (57 %) were female. SH occurred in 37 % of the patients after PTX. Using a multivariate stepwise logistic regression analysis, lower preoperative levels of Ca (odds ratio 0.69, 95 % CI 0.60-0.79, P < 0.001), higher preoperative levels of iPTH (odds ratio 1.04, 95 % CI 1.00-1.07, P = 0.048), P (odds ratio 2.43, 95 % CI 1.49-3.95, P < 0.001) and ALP (odds ratio 1.08, 95 % CI 1.05-1.11, P < 0.001) were found to be independent predictors of occurrence of SH following PTX. CONCLUSIONS: The readily obtainable preoperative laboratory parameters including Ca, iPTH, P, and ALP will allow identification of a subgroup of patients who are at greater risk for the development of SH following PTX.

Combined alkaline phosphatase and phosphorus levels as a predictor of mortality in maintenance hemodialysis patients.

Hyperphosphatemia-induced vascular calcification and higher alkaline phosphatase (ALP) levels-related high-turnover bone diseases are linked to mortality among patients with chronic kidney disease (CKD). Nonetheless, no large epidemiological study in patients with CKD has been conducted to investigate the interaction and joint effect of hyperphosphatemia and higher ALP levels on mortality.We analyzed 11,912 maintenance hemodialysis patients from January 2005 to December 2010. Unadjusted and adjusted hazard ratios (aHRs) of death were calculated for different categories of serum phosphorus and ALP using the Cox regression model. The modification effect between serum phosphorus and ALP on mortality was determined using an interaction product term.Both hypophosphatemia (<3.0 mg/dL) and hyperphosphatemia (>7.0 mg/dL) were associated with incremental risks of death (aHR: 1.25 [95% confidence intervals (CIs): 1.09-1.44], and 1.15 [95% CI: 1.01-1.31], respectively) compared to the lowest hazard ratio (HR) group (5 mg/dL ≤ phosphorus<6 mg/dL). ALP levels were linearly associated with incremental risks for death (aHR: 1.58 [95% CI: 1.41-1.76] for the category of ALP>150 U/L). In the stratified analysis, patients with combined higher ALP (>150 U/L) and hyperphosphatemia (>7.0 mg/dL) had the greatest mortality risk (aHR: 2.25 [95% CI: 1.69-2.98] compared to the lowest HR group (ALP ≤ 60 U/L and 4 mg/dL ≤ phosphorus<5 mg/dL). Although the effect of hyperphosphatemia on mortality seemed stronger in higher ALP levels, the interaction was not statistically significant (P=0.22).The association between serum phosphorus levels and mortality was not limited to higher ALP levels. Regardless of serum ALP levels, we may control serum phosphorus levels merely toward the normal range. While considering the joint effect of ALP and hyperphosphatemia on mortality, the optimal phosphorus range should be stricter.

Short- and long-term impact of subtotal parathyroidectomy on the achievement of bone and mineral parameters recommended by clinical practice guidelines in dialysis patients: a 12-year single-center experience.

BACKGROUND/AIMS: The short- and long-term impact of parathyroidectomy (PTX) on the parameters of mineral bone disease in dialysis patients with severe secondary hyperparathyroidism (HPT) remains unclear. METHODS: A retrospective chart review of 401 consecutive dialysis patients who underwent subtotal PTX by one surgeon was performed. We checked serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) for 3 consecutive days, and then monthly for Ca, P, and tri-monthly for iPTH postoperatively. Patients with available laboratory data within the 1st to 6th postoperative months were included in the short-term follow-up group and those with at least 6 months available data were in the long-term follow-up one. RESULTS: Patients (short-term group, n = 401, and long-term group, n = 94) had severely uncontrolled serum iPTH levels, Ca, P and Ca × P before PTX. In the short-term group, percentages of cases achieving K/DOQI targets for serum Ca, Ca × P, and iPTH and KDIGO ones for serum Ca, P, and iPTH after PTX, significantly improved compared with those before operation (all p < 0.05). In the long-term group (mean follow-up of 43 ± 29 months), the percentage of achieved targets for serum iPTH in both guidelines and for serum Ca and Ca × P in the K/DOQI recommendation also improved postoperatively (all p < 0.05). CONCLUSIONS: Achievements of K/DOQI recommended values for serum Ca, Ca × P, iPTH and KDIGO recommendations for iPTH can be successfully reached by subtotal PTX in medically refractory, secondary HPT in dialysis patients both during short- and long-term follow-ups.

N-acetylcysteine for the management of anemia and oxidative stress in hemodialysis patients.

BACKGROUND/AIMS: To explore the efficacy of oral N-acetylcysteine (NAC) supplementation for anemia and oxidative stress in hemodialysis (HD) patients. METHODS: Of the eligible patients (n = 325) in an outpatient HD unit, 49 received NAC 200 mg orally thrice a day during the first 3 months, while the other 276 patients not receiving NAC were observed. RESULTS: During the 4-month study, 11 patients receiving NAC withdrew but had no severe adverse effects, while 49 patients not receiving NAC had negative confounding events. Thus only the data of the remaining patients, 38 taking NAC and 227 not taking NAC, were analyzed for efficacy. The demographic and laboratory data of both groups were similar at baseline. When the erythropoietin dosage was stable throughout, only the NAC group had a significant increase in hematocrit, accompanied with a decrease in plasma levels of 8-isoprostane and oxidized low-density lipoprotein. Analyzed as a nested case-control study, NAC supplementation was also found to be a significant predictor of positive outcomes in uremic anemia. CONCLUSIONS: Oral NAC supplementation may be a promising therapy for uremic anemia and oxidative stress in HD patients.

Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis.

BACKGROUND: T-cell damage by increased oxidative stress in end-stage renal disease (ESRD) patients undergoing chronic haemodialysis (HD) led to the increased T-cell apoptosis and the alteration of surface markers and Th1/Th2 ratio in CD4(+) T lymphocytes. Antioxidant electrolysed-reduced water (ERW) was used as the dialysate in ESRD patients undergoing chronic HD to test for improved oxidative stress-related T-cell apoptosis, alterations of surface markers and intracellular cytokine profile. METHODS: We evaluated apoptosis formation by annexin V, CD25-related surface markers, and cytokine ratio of Th1/Th2 in CD4(+) T lymphocytes and Tc1/Tc2 in CD8(+) T lymphocytes of 42 ESRD patients haemodialysed with ERW for 1 year. RESULTS: In comparison to 12 healthy individuals, the ESRD patients had more T-cell apoptosis and less CD3(+), CD4(+) and CD8(+) T cells and CD25/CD69/CD94/CD3(+) phenotypes at baseline. Lower intracellular IL-2 and IFN-gamma levels in the Th1/CD4(+) and Tc1/CD8(+) cells and higher intracellular IL-4, IL-6 and IL-10 levels in the Th2/CD4(+) and Tc2/CD8(+) cells were also noted in the ESRD patients. After a 1-year ERW treatment, the patients had a decrease in T-cell apoptosis and increases in CD3(+), CD4(+) and CD8(+) cell numbers and CD25/CD69/CD94/CD3(+) phenotypes in the T cells. The intracellular IL-2 and IFN-gamma levels in the Th1/Tc1 cells significantly (P < 0.05) increased and the intracellular IL-4, IL-6 and IL-10 levels in the Th2/Tc2 cells decreased. Furthermore, the Th1/Th2 and Tc1/Tc2 cytokine ratios were improved toward a normal status. CONCLUSION: One-year ERW treatment effectively ameliorated T-cell apoptosis, altered CD25-related surface markers and intracellular cytokine profile in the HD patients.

Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters.

Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-*, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 +/- 51 to 303 +/- 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 +/- 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 +/- 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury.

Chronic green tea extract supplementation reduces hemodialysis-enhanced production of hydrogen peroxide and hypochlorous acid, atherosclerotic factors, and proinflammatory cytokines.

BACKGROUND: Oxidative stress increases in patients with end-stage renal disease and exaggerates the related comorbidities. OBJECTIVE: The aim of the study was to evaluate the effects of supplementation with decaffeinated green tea extract (catechins) on hemodialysis-induced reactive oxygen species, atherosclerotic disease risk factors, and proinflammatory cytokines. DESIGN: We enrolled 6 healthy subjects and 54 hemodialysis patients for the study. First, the pharmacokinetics of one oral dose of catechins was compared between healthy subjects (n = 6) and hemodialysis patients (n = 10). Second, in the 10 hemodialysis patients, we compared the antioxidant effects of 3 different doses (0, 455, and 910 mg) of oral catechins with that of oral vitamin C (500 mg) during a hemodialysis session. Third, the other 44 hemodialysis patients participated in a 7-mo interventional study, in which 30 patients received placebo throughout and 14 patients received catechins (455 mg/d) from the third to the fifth month. RESULTS: After one oral dose, the hemodialysis patients (n = 10) had later peaks and slower decay of plasma catechins than did the healthy subjects. In the 10 hemodialysis patients, catechin supplementation reduced hemodialysis-enhanced plasma hypochlorous acid activity more effectively than did placebo or vitamin C. Between treatments with 455 or 910 mg catechins, no significant difference was found in the reduction of plasma hypochlorous acid activity. Catechins also significantly reduced proinflammatory cytokine expression enhanced by hemodialysis. In the 7-mo interventional study, the 14 patients who received daily supplementation of catechins for 3 mo had less predialysis plasma hydrogen peroxide activity, lower hypochlorous acid activity, and lower phosphatidylcholine hydroperoxide, C-reactive protein, and proinflammatory cytokine concentrations than did the 30 hemodialysis patients who received placebo. CONCLUSION: Catechins reduce hemodialysis-induced production of hydrogen peroxide and hypochlorous acid, atherosclerotic disease risk factors, and proinflammation.