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Serum phosphate and mortality in incident dialysis patients in Australia and New Zealand.
Tiong, MK, Ullah, S, McDonald, SP, Tan, SJ, Lioufas, NM, Roberts, MA, Toussaint, ND
Nephrology (Carlton, Vic.). 2021;(10):814-823
Abstract
AIM: Hyperphosphataemia is associated with increased adverse outcomes, including mortality. Re-examining this association using up-to-date data reflecting current and real-world practices, across different global regions and in both haemodialysis and peritoneal dialysis patients, is important. METHODS We describe the association between serum phosphate and all-cause and cardiovascular mortality in incident dialysis patients between 2008 and 2018 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Time-dependent Cox proportionate hazards models were used. Models were adjusted for available covariates and fitted for the overall cohort, and also each dialysis modality. RESULTS 31 989 patients were followed over 97 122 person-years at risk (mean age at first dialysis 61 years, 38% female, 67% haemodialysis). We observed a U-shaped association between serum phosphate and all-cause mortality. In the fully adjusted model, categories of serum phosphate above and below 1.25-1.99 mmol/L were associated with progressively higher risk, reaching a hazard ratio of 2.13 (95% CI 1.93-2.36, p < .001) for serum phosphate ≥2.75 mmol/L, and 1.56 (95% CI 1.44-1.69, p < .001) for serum phosphate <1.00 mmol/L. Low and high levels of serum phosphate were also associated with increased risk of cardiovascular mortality, however the association with high serum phosphate was more pronounced ("J-shaped relationship"). The associations were consistent across sub-analyses of patients receiving haemodialysis and peritoneal dialysis treatment. CONCLUSION In this large contemporary dialysis cohort, both high and low levels of serum phosphate were independently associated with increased risk of mortality. Future studies are required to determine whether treatment of abnormal serum phosphate levels improves mortality.
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Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial.
Womack, R, Berru, F, Panwar, B, Gutiérrez, OM
Clinical journal of the American Society of Nephrology : CJASN. 2020;(9):1251-1258
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BACKGROUND AND OBJECTIVES Ferric citrate is an oral medication approved for treatment of iron deficiency anemia in patients with CKD not requiring dialysis. The relative efficacy of ferric citrate versus ferrous sulfate in treating iron deficiency in patients with CKD is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We randomized 60 adults with moderate to severe CKD (eGFR 15-45 ml/min per 1.73 m2) and iron deficiency (transferrin saturation [TSAT] ≤30% and ferritin ≤300 ng/ml) to ferric citrate (2 g three times a day with meals, n=30) or ferrous sulfate (325 mg three times a day, n=30) for 12 weeks. Primary outcomes were change in TSAT and ferritin from baseline to 12 weeks. Secondary outcomes were change in hemoglobin, fibroblast growth factor 23 (FGF23), and hepcidin. RESULTS Baseline characteristics were well balanced between study arms. There was a greater increase in TSAT (between-group difference in mean change, 8%; 95% confidence interval [95% CI], 1 to 15; P=0.02) and ferritin (between-group difference in mean change, 37 ng/ml; 95% CI, 10 to 64; P=0.009) from baseline to 12 weeks in participants randomized to ferric citrate as compared with ferrous sulfate. Similarly, as compared with ferrous sulfate, treatment with ferric citrate resulted in a greater increase in hepcidin from baseline to 12 weeks (between-group difference, 69 pg/ml; 95% CI, 8 to 130). There were no between-group differences in mean change for hemoglobin (0.3 g/dl; 95% CI, -0.2 to 0.8), intact FGF23 (-29 pg/ml; 95% CI, -59 to 0.1), or C-terminal FGF23 (61 RU/ml; 95% CI, -181 to 58). The incidence of adverse events did not differ between treatment arms. CONCLUSIONS As compared with ferrous sulfate, treatment with ferric citrate for 12 weeks resulted in a greater mean increase in TSAT and ferritin concentrations in individuals with moderate to severe CKD and iron deficiency. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With Moderate to Severe Chronic Kidney Disease (CKD) With Iron Deficiency, NCT02888171.
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Effects of oral activated charcoal on hyperphosphatemia and vascular calcification in Chinese patients with stage 3-4 chronic kidney disease.
Gao, Y, Wang, G, Li, Y, Lv, C, Wang, Z
Journal of nephrology. 2019;(2):265-272
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BACKGROUND The relationship between oral activated charcoal (OAC) and hyperphosphatemia and vascular calcification is not completely clear. We observed and recorded the effects of OAC on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD). METHODS In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the OAC group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multidetector computed tomography (MDCT) and were randomly divided into three groups: the OAC group, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. RESULTS The first and second phases of the experiment were followed for 12 months. In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X2 = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the OAC group, the CC group and the LC group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01). CONCLUSION Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. OAC appears to delay the development of vascular calcifications in stage 3-4 CKD patients.
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A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis.
Bhargava, R, Kalra, PA, Hann, M, Brenchley, P, Hurst, H, Hutchison, AJ
BMC nephrology. 2019;(1):37
Abstract
BACKGROUND Hyperphosphataemia in dialysis subjects is associated with increased mortality. However cause and effect has not been proven, and the ideal phosphate target range is unknown despite KDOQI's call for studies over 12 years ago. The design and conduct of a randomized controlled trial is challenging because maintaining two groups within differing target ranges of serum phosphate has not been achieved over a long follow-up of 1 year, in a trial setting, before. The SPIRiT study examines the subject acceptance, recruitment and retention rates for such a study in which subjects were randomised to two distinct serum phosphate concentrations, then titrated and maintained over 12 months. METHODS A two center trial of 104 hemodialysis subjects randomized to lower range LRG 0.8-1.4 mmol/L or 2.5-4.3 mg/dL) and higher range (HRG 1.8-2.4 mmol/L or 5.6-7.4 mg/dL) serum phosphate groups. Two months' titration and ten months' maintenance phase. Interventions were non-calcium phosphate binders, self-help questionnaires, with blood tests at specified time intervals. RESULTS Thirteen percent of the eligible dialysis population were successfully recruited. A mean separation by serum phosphate of 1.1 mg/dL was achieved and maintained between the groups over 10 months. Drop-out rate was 27% with mortality 10%. Nine subjects in the HRG (17.6%) and two subjects in the LRG (3.8%) died during the study, however the study was not powered to detect significant differences in outcomes. CONCLUSION Randomizing dialysis subjects to separate treatment targets for serum phosphate can achieve a clinically significant sustained separation over 12 months. A large scale longer term study is required to examine outcomes including mortality. TRIAL REGISTRATION The trial registration number is ISRCTN24741445 - Date of registration 16th January, retrospectively registered.
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Does Adding Various Accelerators to Mineral Trioxide Aggregate Have a Negatively Effect on Push-Out Bond Strength?
İlker, A, Sarıyılmaz, E, Çakici, F
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2019;(1):36-40
Abstract
OBJECTIVE This study compares the effect of the white mineral trioxide aggregate (WMTA) accelerators, including disodium hydrogen orthophosphate (Na2HPO4; 2.5 wt%), calcium chloride (CaCl2; 5 and 10 wt%), and KY jelly, on the push-out bond strength of WMTA. The null hypothesis was that the WMTA accelerators would not affect the push-out bond strength of WMTA. MATERIALS AND METHODS Slices (2-mm-thick) were obtained from 75 human mandibular molar distal roots. The slices were enlarged up to size 6 Gates-Glidden burs to obtain a 1.5-mm canal diameter. The slices were randomly divided into 4 experimental groups and a control group (n = 15 in each group). Freshly prepared WMTA mixture was placed into the root slices and stored at 37°C in a 100% humidified atmosphere for 60 days. The force required to dislodge the WMTA cement from the root slice was determined using a universal testing machine. The push-out bond strength was calculated. RESULTS Push- out bond strength of 5- and 10-wt% CaCl2, and 2.5-wt% Na2HPO4 WMTA groups was significantly lower than in the KY-jelly and control groups (p < 0.05). The mean push-out bond strength of KY jelly was lower than in the control group but not statistically significant. CONCLUSION The addition of KY jelly to WMTA did not have an adverse effect on the push-out bond strength of WMTA, in contrast to the other accelerators, including Na2HPO4 and CaCl2, which reduced the push-out bond strength.
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Comparative Efficacy and Safety of Phosphate Binders in Hyperphosphatemia Patients With Chronic Kidney Disease.
Yang, X, Bai, Q, Li, Y, Liu, H, Guo, H, Zhang, X
JPEN. Journal of parenteral and enteral nutrition. 2018;(4):766-777
Abstract
BACKGROUND In this study, we coordinated a network meta-analysis to establish the efficacy and safety of different agents used in the treatment of hyperphosphatemia patients with chronic kidney disease. METHODS PubMed, CNKI, and Embase were systematically searched to retrieve relevant studies. Outcomes were presented by mean differences, odds ratios, and corresponding 95% credible intervals for continuous outcomes and binary outcomes, respectively. Each therapy was ranked according to the value of surface under the cumulative ranking curve. Consistencies between direct and indirect comparisons were assessed with a node-splitting plot. RESULTS In terms of efficacy end points (including levels of serum phosphate, serum calcium, serum intact parathyroid hormone, and serum calcium × phosphorus product), all 7 kinds of agents outperformed or performed at least equally to placebo, with iron-based phosphate-binding agents being potentially the most effective. As for safety end points (including mortality, adverse events, and all-cause discontinuation), almost all agents were equivalent in term of mortality and all-cause discontinuation except in the comparison between iron-based phosphate-binding agents and placebo. Meanwhile, iron-based phosphate-binding agents colestilan and nicotinic acid performed poorly compared with placebo in terms of adverse events. Furthermore, iron-based phosphate-binding agents were potentially the safest agents followed sequentially by calcium-based phosphate-binding agents and placebo. CONCLUSION Iron-based phosphate-binding agents were the preferable agents when considering efficacy and safety simultaneously.
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Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism.
Saeedi, R, Mojebi-Mogharar, A, Sandhu, SK, Dubland, JA, Ford, JA, Yousefi, M, Pudek, M, Holmes, DT, Erb, SR, Peter Kwan, W, et al
Annals of hepatology. 2017;(2):207-214
Abstract
BACKGROUND Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.
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Effects of lanthanum carbonate and calcium carbonate on fibroblast growth factor 23 and hepcidin levels in chronic hemodialysis patients.
Chang, YM, Tsai, SC, Shiao, CC, Liou, HH, Yang, CL, Tung, NY, Hsu, KS, Chen, IL, Liu, MC, Kao, JL, et al
Clinical and experimental nephrology. 2017;(5):908-916
Abstract
BACKGROUND Phosphate binders have an impact on fibroblast growth factor 23 (FGF23); however, the effect of phosphate binders on serum hepcidin has not been explored. We conducted a 24-week multicenter randomized controlled trial to investigate the effects of lanthanum carbonate or calcium carbonate monotherapy on serum phosphate, FGF23, and hepcidin levels in chronic hemodialysis patients. METHODS Forty-six patients were recruited, and daily dietary phosphorus was controlled between 600-800 mg. Serum calcium, phosphate, albumin, alkaline phosphatase (ALP), FGF23, intact parathyroid hormone (iPTH), hepcidin, high-sensitivity CRP (hsCRP), 25(OH)D, 1,25(OH)2D, fetuin-A, and osteopontin were checked as scheduled. RESULTS Twenty-five patients completed the study. Mean serum FGF23 level was significantly decreased after a 24-week treatment with lanthanum (8677.5 ± 7490.0 vs. 4692.8 ± 5348.3 pg/mL, p = 0.013, n = 13), but not with calcium (n = 12). The reduction of serum hepcidin in lanthanum group was positively correlated with the decrement of serum phosphate (r = 0.631, p = 0.021) and serum hsCRP (r = 0.670, p = 0.012) levels, respectively. Serum ALP, iPTH, vitamin D, fetuin-A, and osteopontin revealed no significant inter- or intragroup differences. CONCLUSIONS In summary, a decrease in serum FGF23 levels and a trend of decline in hepcidin levels were observed only in lanthanum group.
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Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study.
Ako, S, Takemoto, K, Yasutomi, E, Sakaguchi, C, Murakami, M, Sunami, T, Oka, S, Kenta, H, Okazaki, N, Baba, Y, et al
World journal of gastroenterology. 2017;(24):4454-4461
Abstract
AIM: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy. METHODS Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS Although NaP showed better tolerability in terms of taste, volume and overall impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.
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Design and baseline characteristics of the LANDMARK study.
Ogata, H, Fukagawa, M, Hirakata, H, Kaneda, H, Kagimura, T, Akizawa, T, ,
Clinical and experimental nephrology. 2017;(3):531-537
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BACKGROUND Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. METHODS The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5-6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range. If the target serum P level was not achieved, non-Ca-based P binders (other than LC) could also be added. The primary endpoint is survival time free of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction or stroke, and unstable angina. RESULTS Overall, 2309 patients were allocated to the LC (N = 1154) or CC group (N = 1155). At baseline, the mean age was 68.4 years, 40.4 % were women, 55.9 % had diabetes, 18.3 % had a history of ischemic heart disease, and 13.9 % had cerebrovascular disease. A total of 184 patients (8.4 %) had undergone coronary intervention procedures. Baseline characteristics were well balanced between groups. CONCLUSIONS The LANDMARK study will determine whether LC, a non-Ca-based P binder, reduces cardiovascular mortality and morbidity in chronic hemodialysis patients.