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1.
The impact of an acute oral phosphate load on endothelium dependent and independent brachial artery vasodilation in healthy males.
Levac, BM, Adams, MA, Pyke, KE
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2017;(12):1307-1315
Abstract
Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (flow-mediated dilation; FMD) and -independent (glyceryl trinitrate; GTN)) vasodilation in young, healthy males. Seventeen healthy male participants (age, 23 ± 3 years) were exposed to an oral load of phosphate (PHOS; liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over 2 experimental days. A brachial artery FMD test was performed pre-ingestion and at 20 min, 60 min, and 120 min following the ingestion of the phosphate load or the placebo. GTN tests were performed pre- and 140 min post-ingestion. Serum phosphate was not impacted differently by phosphate versus placebo ingestion (p = 0.780). In contrast, urinary phosphate excretion was markedly increased in the PHOS (p < 0.001) but not in the PLAC condition (p = 0.130) (Δ fractional excretion of phosphate in PHOS (29.2%) vs. PLAC (9.3%)). This indicates that circulating phosphate levels were homeostatically regulated. GTN-mediated vasodilation was not significantly affected by phosphate ingestion. In primary analysis no impact of phosphate ingestion on FMD was detected. However, when the shear stress stimulus was added as a covariate in a subset of participants, exploratory pairwise comparisons revealed a significantly lower FMD 20 min post-phosphate ingestion versus placebo (p = 0.024). The effects of phosphate ingestion on FMD and serum phosphate are in contrast with previous findings and the mechanisms that underlie the disparate results require further investigation.
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2.
Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.
Morabito, S, Pistolesi, V, Tritapepe, L, Vitaliano, E, Zeppilli, L, Polistena, F, Fiaccadori, E, Pierucci, A
BMC nephrology. 2013;:232
Abstract
BACKGROUND Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted. RESULTS Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.
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3.
Potentially modifiable factors associated with non-adherence to phosphate binder use in patients on hemodialysis.
Martins, MT, Silva, LF, Kraychete, A, Reis, D, Dias, L, Schnitman, G, Oliveira, L, Lopes, GB, Lopes, AA
BMC nephrology. 2013;:208
Abstract
BACKGROUND Despite the evidence that phosphate binder (PB) is associated with improved outcomes many hemodialysis patients do not adhere to prescribed PB regimen. Therefore, barriers to PB adherence should be identified and eliminated. The purpose of this study was to evaluate PB adherence among hemodialysis patients and to explore potentially modifiable factors associated with low PB adherence. METHODS A cross-sectional study (502 patients) was performed in four dialysis units in Salvador, Brazil, using data from the second phase of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO). Patients were categorized as adherent or non-adherent to PB based on their responses to a semi-structured questionnaire. RESULTS Non-adherence to PB was observed for 65.7% of the patients. After adjustments for numerous covariates, cerebrovascular disease (odds ratio (OR), 3.30; 95% confidence interval (CI), 1.03-10.61), higher PTH (OR per each 300 pg/mL, 1.14; 95% CI, 1.01-1.28), lack of comprehension of the appropriate time to use PB (OR, 7.09; 95% CI, 2.10-23.95) and stopping PB use after feeling better (OR, 4.54; 95% CI, 1.45-14.25) or feeling worse (OR, 11.04; 95% CI, 1.79- 68.03) were significantly associated with PB non-adherence. By contrast, the adjusted odds of PB non-adherence were lower for patients with more years on dialysis (OR by each 2 years, 0.87; 95% CI, 0.80-0.95), with serum phosphorus above 5.5 mg/dL (OR, 0.53; 95% CI 0.34-0.82), who referred that were encouraged by the dialysis staff to be independent (OR, 0.52; 95% CI 0.30-0.90), and reported that the nephrologist explained how PB should be used (OR, 0.20; 95% CI 0.05-0.73). CONCLUSION The results of the present study are encouraging by showing evidence that improvement in the care provided by the dialysis staff and the attending nephrologist may play an important role in reducing the high prevalence of non-adherence to PB in maintenance hemodialysis patients. A new questionnaire is presented and may help to evaluate systematically the patients regarding PB adherence in hemodialysis setting.
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4.
Phosphate mass removal during hemodialysis: a comparison between eKT/V-matched conventional and extended dialysis.
Sampaio, MS, Ruzany, F, Dorigo, DM, Suassuna, JH
American journal of nephrology. 2012;(2):121-6
Abstract
BACKGROUND AND OBJECTIVES The control of hyperphosphatemia is an unmet need in dialysis care. Compared to conventional hemodialysis (cHD), extended hemodialysis (eHD) appears to more easily control blood phosphate levels in chronically dialyzed patients. Here, we sought to compare eKT/V-matched cHD and eHD procedures in order to quantify the contribution of dialysis prescription and time in the mass removal of phosphate. METHODS Eight stable hemodialysis patients with negligible residual renal function underwent cHD and eHD sessions adjusted to provide the same eKT/V(urea). Total dialysate, total and hourly partial dialysate and blood samples were collected for comparison of mass extraction of urea, creatinine, and phosphate. RESULTS Mean eKT/V(urea) was similar in eHD and cHD (1.30 vs. 1.28, p = nonsignificant). Likewise, mass removal of urea and creatinine during cHD and eHD were not significantly different. Conversely, phosphate mass removal was 40% higher with eHD as compared to cHD (1,219 ± 262 vs. 858 ± 186 mg, p = 0.015). Although hourly mass removal of phosphate was higher during cHD, the prolonged period of lesser but continuous removal was responsible for higher total phosphate elimination during eHD. CONCLUSION In dialysis sessions matched to provide a similar eKT/V(urea), removal of phosphate increases by 40% when time is extended from 4 to 8 h. Urea-based adequacy models cannot be used to predict the amount of phosphorus removal during hemodialysis.
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5.
Cross-sectional analysis of abnormalities of mineral homeostasis, vitamin D and parathyroid hormone in a cohort of pre-dialysis patients. The chronic renal impairment in Birmingham (CRIB) study.
Zehnder, D, Landray, MJ, Wheeler, DC, Fraser, W, Blackwell, L, Nuttall, S, Hughes, SV, Townend, J, Ferro, C, Baigent, C, et al
Nephron. Clinical practice. 2007;(3):c109-16
Abstract
BACKGROUND Disturbances in mineral and vitamin D metabolism, which affect parathyroid hormone (PTH) synthesis, are well recognized in patients receiving dialysis. However, it is unclear at what stage of chronic kidney disease (CKD) these abnormalities develop. METHODS The associations between CKD stages 3 and 5, and alterations of calcium, phosphate, vitamin D and PTH concentrations were assessed in 249 patients (mean age 61 years, 66% male) and 79 age- and sex-matched healthy controls. RESULTS As compared to controls, serum phosphate concentrations were elevated among CKD patients (1.40 vs. 1.11 mmol/l; p < 0.0001). And levels of both 25-hydroxyvitamin D (42.1 vs. 60.4 nmol/l; p < 0.0001) and 1,25-dihydroxyvitamin D (58.2 vs. 119.5 pmol/l; p < 0.0001) were lower among patients with CKD, even among those with only stage 3 CKD and despite 73% of patients receiving vitamin D supplements. The ratio of 1,25-dihydroxy- to 25-hydroxyvitamin D was lower than controls, even among patients with stage 3 CKD (p = 0.0001), and this ratio diminished with advancing renal impairment. Concomitant elevations were observed in intact PTH (13.8 vs. 4.2 pmol/l; p < 0.0001) and whole PTH (7.9 vs. 2.7 pmol/l; p < 0.0001). CONCLUSION Impaired conversion of 25-hydroxy- to 1,25-dihydroxyvitamin D is an early feature of renal disease, and progresses as renal function deteriorates.
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6.
Deficit in human muscle strength with cast immobilization: contribution of inorganic phosphate.
Pathare, NC, Stevens, JE, Walter, GA, Shah, P, Jayaraman, A, Tillman, SM, Scarborough, MT, Parker Gibbs, C, Vandenborne, K
European journal of applied physiology. 2006;(1):71-8
Abstract
Metabolic factors have been proposed to explain strength deficits observed in skeletal muscle with immobilization that are not completely accounted for by changes in muscle cross-sectional area (CSA) and neural adaptations. The aim of this study was to quantify changes in the resting inorganic phosphate (Pi) concentration from the medial gastrocnemius muscle during immobilization, reloading and rehabilitation. Additionally, we assessed the contributions of CSA, muscle activation and Pi concentration to plantar flexor torque during rehabilitation following immobilization. Eight persons with a surgically stabilized ankle fracture participated. Subjects were immobilized for 6-8 weeks and subsequently participated in 10 weeks of rehabilitation. Localized (31)P-Magnetic resonance spectroscopy, magnetic resonance imaging, isometric torque and activation testing were performed on the immobilized and uninvolved limbs. At 6 weeks of immobilization, significant differences were noted between the immobilized and uninvolved limbs for the Pi concentration and the Pi/PCr ratio (P < 0.05). From 6 weeks of immobilization to 3-5 days of reloading, the increase in Pi concentration (15%, P = 0.26) and Pi/PCr (20%, P = 0.29) was not significant. During rehabilitation, the relative contributions of CSA, muscle activation and Pi concentration to plantarflexor torque were 32, 44 and 40%, respectively. Together, CSA, muscle activation and Pi concentration accounted for 76% of the variance in torque (P < 0.01). In summary, our findings suggest that immobilization, independent of reloading, leads to a significant increase in the resting Pi concentration of human skeletal muscle. Additionally, alterations in resting Pi concentration may contribute to strength deficits with immobilization not accounted for by changes in muscle CSA or neural adaptations.
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7.
Changes in inorganic phosphate and force production in human skeletal muscle after cast immobilization.
Pathare, N, Walter, GA, Stevens, JE, Yang, Z, Okerke, E, Gibbs, JD, Esterhai, JL, Scarborough, MT, Gibbs, CP, Sweeney, HL, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2005;(1):307-14
Abstract
Cast immobilization is associated with decreases in muscle contractile area, specific force, and functional ability. The pathophysiological processes underlying the loss of specific force production as well as the role of metabolic alterations are not well understood. The aim of this study was to quantify changes in the resting energy-rich phosphate content and specific force production after immobilization. (31)P-magnetic resonance spectroscopy, three-dimensional magnetic resonance imaging, and isometric strength testing were performed in healthy subjects and patients with an ankle fracture after 7 wk of immobilization and during rehabilitation. Muscle biopsies were obtained in a subset of patients. After immobilization, there was a significant decrease in the specific plantar flexor torque and a significant increase in the inorganic phosphate (P(i)) concentration (P < 0.001) and the P(i)-to-phosphocreatine (PCr) ratio (P < 0.001). No significant change in the PCr content or basal pH was noted. During rehabilitation, both the P(i) content and the P(i)-to-PCr ratio decreased and specific torque increased, approaching control values after 10 wk of rehabilitation. Regression analysis showed an inverse relationship between the in vivo P(i) concentration and specific torque (r = 0.65, P < 0.01). In vitro force mechanics performed on skinned human muscle fibers demonstrated that varying the P(i) levels within the ranges observed across individuals in vivo (4-10 mM) changed force production by approximately 16%. In summary, our findings clearly depict a change in the resting energy-rich phosphate content of skeletal muscle with immobilization, which may negatively impact its force generation.
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8.
Calcium and phosphate balance with quotidian hemodialysis.
Lindsay, RM, Alhejaili, F, Nesrallah, G, Leitch, R, Clement, L, Heidenheim, AP, Kortas, C
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2003;(1 Suppl):24-9
Abstract
BACKGROUND Conventional hemodialysis (HD) is associated with profound disturbances in calcium and phosphate metabolism and abnormal parathyroid hormone (PTH) levels. Effects of more frequent HD on calcium and phosphate balance have not been fully elucidated. METHODS The London Daily/Nocturnal Hemodialysis Study examined effects of quotidian HD, either daily HD (n = 11) or nocturnal HD (n = 12), on calcium and phosphate metabolism, bone alkaline phosphatase levels, and intact PTH (iPTH) levels. RESULTS Daily HD patients showed a slight decrease in predialysis serum phosphate levels, no changes in phosphate-binder requirements or serum calcium levels, and slight increases in serum bone alkaline phosphatase and iPTH levels. Nocturnal HD patients showed a trend for decreased predialysis phosphate levels, with significantly lower values than daily HD and matched control patients on conventional HD therapy at several times. Phosphate-binder use by nocturnal HD patients was significantly reduced. Both quotidian HD groups showed decreases in calcium x phosphate product, with significantly lower values for nocturnal HD patients (38.11 mg(2)/dL(2)) compared with daily HD and control patients (53.99 and 52.51 mg(2)/dL(2), respectively) at 18 months. Bone alkaline phosphatase levels increased slightly and attained statistical significance compared with baseline values for both quotidian HD groups. A trend for increases in serum iPTH levels, coupled with increasing levels of bone alkaline phosphatase in nocturnal HD patients, led to the decision to increase the dialysate calcium concentration from 5.0 to 7.0 mg/dL. This 1-time adjustment resulted in a reversal of the trend and a return to baseline values. CONCLUSION This study shows the superior control of serum phosphate levels in nocturnal HD patients compared with daily HD or conventional HD patients and the benefits of dialysate with a greater calcium concentration in slow nocturnal HD.
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9.
Phosphatemic control during acute renal failure: intermittent hemodialysis versus continuous hemodiafiltration.
Tan, HK, Bellomo, R, M'Pis, DA, Ronco, C
The International journal of artificial organs. 2001;(4):186-91
Abstract
BACKGROUND Achieving "adequacy of dialysis" includes the maintenance of normal serum phosphate concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum phosphate concentrations using daily morning blood tests in 88 consecutive intensive care patients half of which were treated with IHD and half with CRRT RESULTS Mean patient age was 54+/-14 years for IHD and 60+/-14 years for CVVHDF (NS). However, patients who received CVVHDF were more critically ill (mean APACHE II scores: 24.4+/-5.1 for IHD vs. 29.2+/-5.7 for CVVHDF, p<0.003). Before treatment, the serum phosphate concentration was 2.04+/-0.16 mmoll L for IHD and 1.96+/-0.17 mmoll L for CVVHDF (NS), with abnormal values in 79.4% of IHD patients and in 64.8% of CVVHDF patients (NS). During treatment, CVVHDF induced a greater reduction in serum phosphate (p=0.02) during the first 48 hours and conferred superior subsequent control of hyperphosphatemia (achieved in 64.6% of observations during CVVHDF vs. 41.8% during IHD; p<0.0001). The serum phosphate concentration was also more likely to be within the normal range during CVVHDF (55.3% vs.36.2%; p<0.0001). There was a trend toward more frequent hypophosphatemia (9.3% vs. 5.6%; P<0.1) during CVVHDF CONCLUSIONS Abnormal serum phosphate concentrations are frequent in ARF patients before and during renal replacement, however, normalization of phosphatemia is achieved more frequently with CVVHDF.