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Modification and Validation of the Phosphate Removal Model: A Multicenter Study.
Zhang, W, Du, Q, Xiao, J, Bi, Z, Yu, C, Ye, Z, Wang, M, Chen, J
Kidney & blood pressure research. 2021;(1):53-62
Abstract
BACKGROUND Our research group has previously reported a noninvasive model that estimates phosphate removal within a 4-h hemodialysis (HD) treatment. The aim of this study was to modify the original model and validate the accuracy of the new model of phosphate removal for HD and hemodiafiltration (HDF) treatment. METHODS A total of 109 HD patients from 3 HD centers were enrolled. The actual phosphate removal amount was calculated using the area under the dialysate phosphate concentration time curve. Model modification was executed using second-order multivariable polynomial regression analysis to obtain a new parameter for dialyzer phosphate clearance. Bias, precision, and accuracy were measured in the internal and external validation to determine the performance of the modified model. RESULTS Mean age of the enrolled patients was 63 ± 12 years, and 67 (61.5%) were male. Phosphate removal was 19.06 ± 8.12 mmol and 17.38 ± 6.75 mmol in 4-h HD and HDF treatments, respectively, with no significant difference. The modified phosphate removal model was expressed as Tpo4 = 80.3 × C45 - 0.024 × age + 0.07 × weight + β × clearance - 8.14 (β = 6.231 × 10-3 × clearance - 1.886 × 10-5 × clearance2 - 0.467), where C45 was the phosphate concentration in the spent dialysate measured at the 45th minute of HD and clearance was the phosphate clearance of the dialyzer. Internal validation indicated that the new model was superior to the original model with a significantly smaller bias and higher accuracy. External validation showed that R2, bias, and accuracy were not significantly different than those of internal validation. CONCLUSIONS A new model was generated to quantify phosphate removal by 4-h HD and HDF with a dialyzer surface area of 1.3-1.8 m2. This modified model would contribute to the evaluation of phosphate balance and individualized therapy of hyperphosphatemia.
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The effect of lanthanum carbonate on calciprotein particles in hemodialysis patients.
Nakamura, K, Nagata, Y, Hiroyoshi, T, Isoyama, N, Fujikawa, K, Miura, Y, Matsuyama, H, Kuro-O, M
Clinical and experimental nephrology. 2020;(4):323-329
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BACKGROUND Aggregation of solid-phase calcium-phosphate and fetuin-A form nanoparticles called calciprotein particles (CPP). Serum CPP levels are increased in CKD patients and correlated with vascular stiffness and calcification. In this study, we evaluated effects of lanthanum carbonate (LC) and calcium carbonate (CC) on serum CPP levels in hemodialysis (HD) patients. METHODS Twenty-four (24) HD patients (50% men, age; 68 ± 12 years, dialysis period; 6.2 ± 4.8 years, Kt/v; 1.74 ± 0.34) were treated with CC during 0-8 weeks and then switched to LC during 9-16 weeks. Blood samples were obtained at 0, 8, 16 weeks. Serum CPP levels (TCPP) were measured by the gel-filtration method. Low-density CPP (LCPP) levels were determined by centrifuging the serum samples at 16,000 g for 2 h and measuring CPP levels in the supernatant. The difference between TCPP and LCPP was defined as the high-density CPP (HCPP) level. We evaluated association of TCPP, LCPP, and HCPP with serum calcium (Ca), phosphorus (P), intact PTH, FGF23, Klotho, fetuin-A, aortic calcification index (ACI), LDL cholesterol, and hs-CRP. RESULTS TCPP and LCPP levels were significantly decreased after switching CC to LC, whereas Ca and P levels were not changed. HCPP levels were below the lower limit quantification in all patients. The changes in P, Ca × P, LDL cholesterol, but not ACI and the changes in hs-CRP, were correlated with the change in TCPP levels. CONCLUSION The TCPP levels were significantly decreased after switching CC to LC. Non-calcium-containing phosphate binders may be preferable for lowering CPP levels.
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Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial.
Block, GA, Rosenbaum, DP, Yan, A, Chertow, GM
Journal of the American Society of Nephrology : JASN. 2019;(4):641-652
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BACKGROUND Guidelines recommend reducing elevated serum phosphate in patients with CKD. Tenapanor, a minimally absorbed inhibitor of gastrointestinal sodium/hydrogen exchanger 3 (NHE3), reduces paracellular phosphate transport. METHODS In this phase 3 randomized, double-blind trial, we randomly assigned patients with hyperphosphatemia receiving maintenance hemodialysis to receive twice-daily oral tenapanor (3, 10, or 30 mg [the latter down-titrated, if needed]) for 8 weeks. Patients were then rerandomized 1:1 to receive either their previously assigned dose or placebo for a 4-week 'withdrawal' period. We measured serum phosphate levels over the course of the trial. The primary end point was mean change in serum phosphate over the 4-week withdrawal period for the tenapanor group (using pooled data) versus the placebo group. RESULTS Of 219 patients randomized, 152 completed both study phases. During the initial 8-week treatment period, all three treatment groups experienced significant decreases in mean serum phosphate (reductions of 1.00, 1.02, and 1.19 mg/dl, corresponding to the 3, 10, and 30 mg [down-titrated] dose groups, respectively). Tenapanor also showed a significant benefit over placebo during the withdrawal period, with a mean increase of 0.85 mg/dl in the placebo group versus a mean increase of 0.02 mg/dl in the pooled tenapanor group. Adverse events were largely limited to softened stool and a modest increase in bowel movement frequency, resulting from increased stool sodium and water content, stemming from tenapanor's mechanism of action. CONCLUSIONS Tenapanor significantly reduced elevated serum phosphate in patients with hyperphosphatemia receiving maintenance hemodialysis. Adverse effects were limited to those induced by its known mechanism of action, which increases stool sodium and water content.
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Interventional study to improve adherence to phosphate binder treatment in dialysis patients.
Hjemås, BJ, Bøvre, K, Mathiesen, L, Lindstrøm, JC, Bjerknes, K
BMC nephrology. 2019;(1):178
Abstract
BACKGROUND Adherence to phosphate binder treatment is important to prevent high serum phosphate level in chronic dialysis patients. We therefore wanted to investigate patient knowledge, beliefs about and adherence to phosphate binders among these patients and assess whether one-to-one pharmacist-led education and counselling enhance adherence and lead to changes in serum phosphate levels. METHODS A descriptive, interventional, single arm, pre-post study was performed at a hospital in Norway, including chronic dialysis patients aged 18 years or more using phosphate binders. The primary end-point was change in the proportion of patients with serum phosphate below 1.80 mmol/L and the secondary end-points included change in the patient's knowledge, beliefs and adherence after the intervention measured by completion of questionnaires 'Patient Knowledge', Medication Adherence Report Scale (MARS- 5) and Beliefs about Medicines Questionnaire (BMQ). Data was collected both prior to and after one-to-one pharmacist-led education and counselling about their phosphate binders. Other medicines used by the patient was also registered. RESULTS A total of 69 patients were enrolled in the study. After intervention, the probability of serum phosphate being below the target threshold 1.80 mmol/L (5.58 mg/dL) increased, although no significant change in mean serum phosphate levels was seen. On the other hand, the knowledge regarding phosphate binder treatment and the patients' beliefs about the necessity of the treatment increased, while the concerns decreased (BMQ). This effect did not lead to increase in self-reported adherence measured by MARS-5. However the scores were high before the intervention. CONCLUSIONS Short term one-to-one individualized pharmacist-led education and counselling about phosphate binders increased the probability of serum phosphate concentrations being below the target threshold level 1.80 mmol/L (5.58 mg/dL), although not statistically significant. However, it did not decrease the mean serum phosphate level or increase the patients' self-reported adherence. The patients increased their knowledge about the phosphate binder and their understanding of adherence, and were less concerned about the side effects of the medication. TRIAL REGISTRATION ISRCTN52852596 , registered 11 April 2019. The trial was registered retrospectively.
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Effect of Intradialytic Exercise on Hyperphosphatemia and Malnutrition.
Salhab, N, Alrukhaimi, M, Kooman, J, Fiaccadori, E, Aljubori, H, Rizk, R, Karavetian, M
Nutrients. 2019;(10)
Abstract
Intradialytic exercise (IDE) is not routinely prescribed in hemodialysis (HD) units despite its potential benefits on patients' outcomes. This study was the first in the United Arab Emirates to examine the effect of aerobic IDE on hyperphosphatemia, malnutrition, and other health outcomes among HD patients. Participants were chosen from the largest HD unit in Sharjah Emirate for a quasi-experimental intervention with pre and post evaluation. The study lasted for 12 months. Study parameters were collected at baseline, post intervention, and follow-up. The intervention included a moderate-intensity aerobic IDE of 45 min per HD session; intensity was assessed using the Borg Scale. Patients were educated on the importance of exercise. Study outcomes were serum phosphorus (P), malnutrition inflammation score (MIS), quality of life (QOL), and pertinent blood tests. Forty-one eligible consenting HD patients were included in the study. Results at follow-up showed a non-significant reduction in P (p = 0.06) in patients who were hyperphosphatemic at baseline, but not in the sample as whole. MIS did not deteriorate throughout the study (p = 0.97). IDE resulted in a non-significant increase in the QOL visual analogue scale (p = 0.34). To conclude, aerobic IDE for 45 min is safe and could be beneficial, especially for hyperphosphatemic patients.
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Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study.
Clarke, BL, Vokes, TJ, Bilezikian, JP, Shoback, DM, Lagast, H, Mannstadt, M
Endocrine. 2017;(1):273-282
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In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2.0-2.2 mmol/L). Predefined endpoints related to phosphate homeostasis and vitamin D metabolism were analyzed. Serum phosphate levels decreased rapidly from the upper normal range and remained lower with rhPTH(1-84) (P < 0.001 vs. placebo). At week 24, serum calcium-phosphate product was lower with rhPTH(1-84) vs. placebo (P < 0.001). rhPTH(1-84) treatment resulted in significant reductions in oral calcium dose compared with placebo (P < 0.001) while maintaining serum calcium. After pretreatment optimization, baseline serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels were within the normal range in both groups. After 24 weeks, 1,25(OH)2D levels were unchanged in both treatment groups, despite significantly greater reductions in active vitamin D dose in the rhPTH(1-84) group. In hypoparathyroidism, rhPTH(1-84) reduces serum phosphate levels, improves calcium-phosphate product, and maintains 1,25(OH)2D and serum calcium in the normal range while allowing significant reductions in active vitamin D and oral calcium doses.
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Octreotide Is Ineffective in Treating Tumor-Induced Osteomalacia: Results of a Short-Term Therapy.
Ovejero, D, El-Maouche, D, Brillante, BA, Khosravi, A, Gafni, RI, Collins, MT
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017;(8):1667-1671
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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which unregulated hypersecretion of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMT) causes renal phosphate wasting, hypophosphatemia, and osteomalacia. The resulting mineral homeostasis abnormalities and skeletal manifestations can be reversed with surgical resection of the tumor. Unfortunately, PMTs are often difficult to locate, and medical treatment with oral phosphate and vitamin D analogues is either insufficient to manage the disease or not tolerated. Octreotide has been proposed as a potential treatment for TIO due to the presence of somatostatin receptors (SSTR) on PMTs; however, the role of somatostatin signaling in PMTs and the efficacy of treatment of TIOs with somatostatin analogues is not clear. In an effort to evaluate the efficacy of octreotide therapy in TIO, five subjects with TIO were treated with octreotide for 3 days. Blood intact FGF23, phosphate, and 1,25(OH)2 D3 , and tubular reabsorption of phosphate (TRP) were measured at frequent time points during treatment. Octreotide's effects were assessed by comparing group means of the biochemical parameters at each time-point to mean baseline values. There were no significant changes in blood phosphate, FGF23, 1,25(OH)2 D3 , or TRP during octreotide treatment, consistent with a lack of efficacy of octreotide in treating TIO. © 2017 American Society for Bone and Mineral Research.
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Educating your patient helps to control serum phosphate and also save 200 euros per patient.
Rodriguez-Palomares, JR, Japaz Cancino, MC, Blazquez Collado, L, Fiallos Criollo, R, Villabon Ochoa, PM, Sanchez Heras, M, Basterrechea, MA, de Arriba de la Fuente, G
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2017;(1):103-105
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High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23.
Dahlerup, JF, Jacobsen, BA, van der Woude, J, Bark, LÅ, Thomsen, LL, Lindgren, S
Scandinavian journal of gastroenterology. 2016;(11):1332-8
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OBJECTIVE Iron isomaltoside (Monofer(®)) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. MATERIALS AND METHODS The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. RESULTS Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. CONCLUSION Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.
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High-Flux Hemodialysis and High-Volume Hemodiafiltration Improve Serum Calcification Propensity.
Dekker, M, Pasch, A, van der Sande, F, Konings, C, Bachtler, M, Dionisi, M, Meier, M, Kooman, J, Canaud, B
PloS one. 2016;(4):e0151508
Abstract
BACKGROUND Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. METHODS We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. RESULTS We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. CONCLUSIONS HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities.