Phosphate Binders In Hemodialysis Patients Research Articles

#3930 EFFECT OF TWO PHOSPHATE BINDERS ON VITAMIN D LEVELS IN HEMODIALYSIS PATIENTS

Abstract Background and Aims A recent meta-analysis highlighted the impact of different types of phosphate binders on vitamin D metabolism in patients with stage 3 CKD. Sevelamer was associated with lower serum 25(OH) vitamin D levels probably due to reduced intestinal absorption of D3 (cholecalciferol). Corresponding effects of different phosphate binders in hemodialysis patients have not been studied. Method We performed an observational prospective study in which 55 stable hemodialysis patients were followed for 28 months. Patients’ age was 42-91 years old and duration of hemodialysis was 2-312 months. Patients received as phosphate binders sevelamer, sucroferric oxyhydroxide or combination. The type of binders, the administration of D3 supplements, paricalcitol or etecalcetide as well as the biochemical control of the patients were recorded every two months. Serum 25(OH) vitamin D levels and the proportion of patients who required D3 supplementation to maintain 25(OH) vitamin D levels >20ng/mL were assessed. Results At baseline, 60% of patients used sevelamer as phosphate binder, 22% sucroferric oxyhydroxide and 18% combination, while 36% were on D3 supplements. Levels of 25(OH) vitamin D showed a significant increase after the first year of follow-up. (Dstart:16±8ng/ml vs D12months:26±10ng/ml, P = .001). After one year D3 supplementation ratio increased to 48% and remained at these levels until the end of follow-up. Taking paricalcitol or etecalcetide did not affect the results. No differences in 25(OH) vitamin D and D3 supplementation rate levels were observed between those receiving the different binders or the co administration group. No differences were observed in the biochemical markers tested as well as in dialysis adequacy. Conclusion In context of daily clinical practice, no differences were observed in the levels of 25(OH) vitamin D in either patients receiving sevelamer, sucroferric oxyhydroxide or combination of both as phosphate binders. Half of hemodialysis patients require cholecalciferol supplementation to maintain adequate 25(OH)vitamin D levels.

Phosphorus Counting Table for the control of serum phosphorus levels without phosphate binders in hemodialysis patients

Hyperphosphatemia constitutes one of the major problems faced by patients with chronic kidney disease, and nourishment plays a significant role in its control. The present study aimed to evaluate the maintenance of phosphorus serum levels by observing measurements before and after an intervention using the Phosphorus Counting Table(PCT), in hemodialysis patients lacking phosphate binder use. The assessment included fifty individuals on hemodialysis who underwent phosphate binder suspension 30 days prior to the intervention. The participants received food and nutrition education on the PCT tool, which assists in the control of dietary phosphorus intake, and followed its instructions for two months. Fasting blood samples were collected at three moments for phosphorus, total calcium, and parathyroid hormone (PTH) analysis. The study sample was initially analyzed as a whole, then sub-classified into two groups: adherence and non-adherence. At the end of the study, no significant difference in serum phosphorus was observed in the total and the adherence groups (p>0.05). The non-adherence group showed a substantial increase of 0.74mg/dL in serum phosphorus levels and 6.16mg2/dL2 in the calcium-phosphorus product after the intervention. Meanwhile, the calcium-phosphorus product improved from 56.42±11.49mg2/dL2 to 51.05±10.67mg2/dL2 in the adherence group. Serum calcium levels did not change throughout the study in the three groups. A significant increment in PTH serum levels was observed at the end of the study in all groups. The PCT showed to be efficient in the maintenance of serum phosphorus in the individuals who adhered well to the tool, without the administration of phosphate binders. Such a method can assist in patient adherence to treatment and enables better diet flexibility. The present trial was registered under the Brazilian Clinical Trials Registry (Rebec). Registration number: RBR-2vzd48.

Research progress of oral phosphate binders compliance measurement scale for hemodialysis patients

To introduce the concept of medication adherence and its importance in the treatment of hyperphosphatemia. By reviewing the scales for measuring medication adherence on oral phosphate binders in hemodialysis patients, this paper will provide the reference for health care personnel to assess the medication adherence effectively. Key words: Review; Medication treatment adherence; Hemodialysis; Phosphate binder; Scale

Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients.

BackgroundFetuin-A is known as a circulating inhibitor of vascular calcification. Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients is still uncertain.MethodsIn the post-hoc study, we analyzed serum fetuin-A and biochemical factors (Ca, P, i-PTH, hsCRP, TG, LDL-C) in 50 hemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. 23 patients received sevelamer and 27 patients received calcium carbonate.ResultsAfter the 48-week treatment, the sevelamer group had less serum calcium increment, less iPTH decrement, more ALK-P increment, more hsCRP decrement and more LDL-C decrement. There was no significant difference in the serum fetuin-A decrement between two groups. Decreased serum fetuin-A levels were found after 48-week treatment in both groups: from 210.61 (104.73) to 153.85 (38.64) ug/dl, P = 0.003 in sevelamer group, from 203.95 (107.87) to 170.90 (58.02) ug/mL, P =0.002 in calcium group. The decrement in serum fetuin-A (Δfetuin-A) levels was associated with ΔCa (ρ = - 0.230, P = 0.040), ΔiPTH (ρ = 0.306, P = 0.031) and Δalbumin (ρ = 0.408, P = 0.003), not associated with sevelamer use, ΔP and ΔhsCRP.ConclusionAfter long-term sevelamer or calcium carbonate treatment, both groups of maintenance HD patients had lower serum fetuin-A levels. Serum levels of increased calcium, decreased iPTH and decreased albumin were associated with the serum fetuin-A decrement.

Adherence to phosphate binders in hemodialysis patients: prevalence and determinants

Phosphate control is a crucial treatment goal in end-stage renal disease, but poor patient adherence to phosphate binder therapy remains a challenge. This study aimed to estimate the extent of phosphate binder adherence in hemodialysis patients and to identify potential determinants. Phosphate binder adherence was measured blindly in 135 hemodialysis patients for 2 months using the medication event monitoring system. Patient data, gathered at inclusion through medical records, ad hoc questionnaires and the short form (SF)-36 health survey, included: (1) demographics, (2) perceived side-effects, belief in benefit, self-reported adherence to the therapy, (3) knowledge about phosphate binder therapy, (4) social support, and (5) quality of life (SF-36). Phosphatemia data was collected from charts. 'Being adherent' was defined as missing <1 total daily dose/week and 'being totally adherent' as missing <1 total daily dose/week, every week. Mean age of patients was 67 years and 64 % of the sample was male. Over the 2 months, 78 % of the prescribed doses were taken. Every week, about half of patients were adherent. Over the entire 8-week period, 22 % of patients were totally adherent. Mean phosphatemia levels were 0.55 mg/dl lower in adherent than nonadherent patients (4.76 vs. 5.31 mg/dl). Determinants for being totally adherent were living with a partner, higher social support (both were interrelated) and higher physical quality of life. Experiencing intake-related inconvenience negatively affected adherence. The social support and quality of life physical score explained 26 % of the variance in adherence. Phosphate binder nonadherence remains a major problem. Interventions should aim, at least, to improve social support. With few associated factors found and yet low adherence, an individualized approach seems indicated.

Influence of the use of phosphate binders on serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis: A retrospective and prospective study

Hypercalcemia–hyperphosphatemia is an unavoidable consequence of end-stage chronic kidney disease and common in hemodialytic patients. Calcium carbonate (CaCO3) is one type of phosphate binder used widely and prescribed in patients undergoing hemodialysis, aiming to control the levels of calcium and phosphate. These drugs are most effective if taken with meals. This study aimed to evaluate the use of phosphate binders in hemodialysis patients and the factors that influence the success of phosphate binder therapy by experimental studies with retrospective data collection through the medical records and prospectively through the questionnaire and interviews with patients. The research was conducted in the Unit Hemodialysis building floor 8 of Cipto Mangunkusumo Hospital, Jakarta. The data were collected in a retrospective way for two months (January–February 2013) and a prospective study in March–April 2013. Patients included were stage 5 chronic kidney disease patients who underwent hemodialysis in hemodialysis ward of Cipto Mangunkusumo Hospital. Patients who had data of serum levels at the beginning of the use of calcium phosphate and the final data in 2013 got the phosphate binder therapy. ResultsNinety six patients with stage 5 chronic kidney disease who underwent hemodialysis had been using phosphate binder for 3years in average. Patient evaluation showed that hypocalcemia was obtained in 23%; normokalemia in 42.7% and hypercalcemia in 34.3%. While the percentage of patients with hipofosfatemia14, 6%, normofosfatemia 32.3% and 53.1% hyperphosphatemia. Results obtained by the prospective analysis of factors that affect the success of the use of phosphate binder therapy are related to how the routine use of phosphate binders is made by the patient. Chi square test showed a significance of 0.000 (p<0.05), the effect of 54%. ConclusionWe can conclude there are many events happening such as hyperphosphatemia in hemodialysis patients that use phosphate binders. Monitoring of serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis should be performed every month. Education and the role of clinical staff required to assist compliance and therapeutic efficacy of phosphate binder are necessary.

Endotoxin Binding by Sevelamer: Potential Impact on Nutritional Status

Patients on hemodialysis (HD) have a high burden of chronic inflammation induced associated with multiple comorbidities including poor nutritional status. Endotoxin (ET) is a Gram-negative bacterial cell wall component and a potent stimulus for innate immune system activation leading to the transcription of proinflammatory cytokines (e.g., IL-1, IL-6, and TNFα) that adversely affect protein metabolism and nutrition. Several cross-sectional observational studies have found that elevated serum ET concentrations in hemodialysis patients are associated with lower serum albumin, higher proinflammatory cytokine, and C-reactive protein concentrations. Possible sources of ET in the systemic circulation are bacterial translocation from the gastrointestinal tract and iron supplementation, potentially leading to intestinal bacterial overgrowth. Sevelamer is a nonabsorbable hydrogel approved for use as a phosphate binder in HD patients. Reductions in serum ET concentrations in hemodialysis patients have been observed with sevelamer therapy in observational studies and the few published interventional studies. Reduction of ET concentrations was associated with concomitant reductions in TNFα, IL-6, and CRP and improvement in serum albumin in the majority of these small studies. Additional studies are needed to evaluate the potential effects of sevelamer treatment on nutritional status in chronic kidney disease (CKD) patients with elevated ET.

Effect of gastric acid suppression with pantoprazole on the efficacy of calcium carbonate as a phosphate binder in haemodialysis patients

Metallic phosphate binders require acidity to dissociate to the free metallic ion and bind phosphorus. Altered gastric acidity may, therefore, influence phosphate-binding efficacy. We evaluated the clinical effect of pantoprazole on the efficacy of calcium carbonate phosphate binders in haemodialysis patients. The study had two parts: a cross-sectional study (n = 67), and an interventional, crossover, double-blind, randomized, placebo-controlled trial in 26 patients given pantoprazole 40 mg daily or placebo for two consecutive 6-week periods. The cross-sectional study showed no difference between those on and off acid suppressants in phosphate (1.43 ± 0.45 vs 1.46 ± 0.31 mmol/L, P = 0.782) or other parameters except age (72.2 ± 9.8 vs 63.8 ± 14.8 years, P = 0.01). In the interventional study, phosphate was higher during pantoprazole than placebo (1.59 ± 0.3 vs 1.42 ± 0.3 mmol/L, P = 0.005). Serum calcium (2.37 ± 0.2 vs 2.46 ± 0.2 mmol/L, P = 0.012) and ionized calcium (1.17 ± 0.1 vs 1.22 ± 0.1 mmol/L, P = 0.013) were lower during pantoprazole treatment. CaxPO(4) (3.76 ± 0.7 vs 3.48 ± 0.7 mmol(2) /L(2) , P = 0.032) and intact parathyroid hormone (31.9 ± 21.4 vs 23.6 ± 17.7 pmol/L, P = 0.004) were higher on pantoprazole. These results demonstrate clinical evidence for an adverse effect of gastric acid suppression on the effectiveness of calcium carbonate phosphate binders. Given their frequent co-prescription, this interaction may be a minor but common reason why some patients fail to control hyperphosphataemia. Clinicians should regularly assess the need for acid suppressants. Further studies are needed to investigate interactions with other phosphate binders.

Effect of gastric acid suppression with pantoprazole on the efficacy of sevelamer hydrochloride as a phosphate binder in haemodialysis patients: A pilot study

Sevelamer hydrochloride (HCL) is thought to require an appropriately acidic environment in order to bind gastrointestinal phosphate. Changes in gastric acidity with acid suppressants may therefore alter the efficacy of sevelamer HCL. Given the widespread use of acid suppression therapy in chronic kidney disease patients, there is potential for a common significant drug interaction to occur. This pilot study evaluated the in vivo effect of gastric acid suppression with pantoprazole on the efficacy of sevelamer HCL as a phosphate binder in maintenance haemodialysis patients. The study protocol was a cross-over, double-blinded, randomized, placebo-controlled trial in 10 haemodialysis patients randomly assigned to pantoprazole 40 mg daily or placebo for two consecutive 6-week periods. Serum phosphate was not significantly altered during pantoprazole compared with placebo treatment (1.61 ± 0.45 mmol/L vs 1.76 ± 0.42 mmol/L, P = 0.204). There were no differences in serum calcium, parathyroid hormone and bicarbonate. This pilot study demonstrates preliminary in vivo evidence for no effect of gastric acid suppression on the effectiveness of sevelamer HCL. Our results are limited by small sample size and therefore, larger experimental studies should be conducted. Although our study did not find a significant drug interaction, given the high prevalence of acid suppressant use in dialysis patients, physicians should be aware of the potential influence of acid suppression on the efficacy of phosphate binders and regularly assess the clinical need for acid suppression therapy.

Comparison of Sevelamer Hydrochloride With Colestimide, Administered Alone or in Combination With Calcium Carbonate, in Patients on Hemodialysis

Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification, serum phosphate (Pi) levels must be controlled by phosphate binders. Although sevelamer and colestimide are known as similar non-calcium, non-aluminum phosphate binders in hemodialysis patients, there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate (CaCO3). We randomly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer (3.0 g/day) and colestimide (3.0 g/day). During the study, 35 subjects dropped out, leaving 13 in the sevelamer group and 14 in the colestimide group. After a 2-week CaCO3 washout, all subjects received the monotherapy for 4 weeks and then CaCO3 (3.0 g/day) was added for another 4 weeks. Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy, but there was no significant difference between the two groups after the addition of CaCO3. Although the calcium x phosphorus product (Ca x P) in the two groups increased during the washout period, there was no significant change or difference between the two groups during monotherapy. However, the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups, and significantly lowered Ca x P only in the sevelamer group, but not in the colestimide group(.) In this short-term study, sevelamer and colestimide similarly ameliorated hyperphosphatemia, but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product, and it may improve cardiovascular mortality in hemodialysis patients.

Sevelamer Hydrochloride Use and Circulating Endotoxin and Inflammatory Biomarkers in Hemodialysis Patients: A Preliminary Report

Chronic inflammation is prevalent among patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). Endotoxin (ET) is a potent inflammatory mediator released by naturally occurring bacteria in the intestinal tract, and ET has been detected in patients with CKD. Uremia-induced impairment of the intestinal mucosa raises the potential of ET exposure in patients with CKD as a result of bacterial translocation. Sevelamer hydrochloride (SH) is a commonly used phosphate binder in HD patients that has also been shown to reduce C-reactive protein (CRP) levels.

Magnesium Carbonate Is an Effective Phosphate Binder for Chronic Hemodialysis Patients: A Pilot Study

This study was designed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients. This study was a prospective, randomized, open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder. This study involved outpatient hemodialysis. We recruited 30 stable hemodialysis patients without a history of frequent diarrhea. After receiving informed consent, we randomized patients 2:1 to magnesium carbonate versus calcium acetate. The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) phosphate target of <5.5 mg/dL. The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus, along with the daily elemental calcium intake, were the primary outcome measures. Magnesium carbonate provided equal control of serum phosphorus (70.6% of the magnebind group and 62.5% of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase), while significantly reducing daily elemental calcium ingestion from phosphate binders (908 +/- 24 vs. 1743 +/- 37 mg/day, P < .0001). Magnesium carbonate was generally well-tolerated in this selected patient population, and was effective in controlling serum phosphorus while reducing elemental calcium ingestion.

Sevelamer with and without calcium and vitamin D: Observations from a long-term open-label clinical trial

Objective: To determine the effects of sevelamer hydrochloride on serum phosphorus, calcium, calcium x phosphate product, and parathyroid hormone (PTH) in patients treated with and without vitamin D metabolites and calcium supplementation. Design: Long-term, open-label clinical trial. Setting: Hemodialysis units. Patients: One hundred ninety-two adult patients with end-stage renal disease on hemodialysis. Intervention: An extended treatment period of sevelamer hydrochloride, preceded and followed by phosphate binder washout periods. Main outcome measures: Treatment-related changes in serum phosphorus, calcium, calcium x phosphate product, and PTH. Results: Subjects treated with sevelamer alone, sevelamer with vitamin D metabolites (with or without calcium), and sevelamer with calcium without vitamin D experienced significant reductions in mean serum phosphorus (range, −2.1 to −2.9 mg/dL) and the calcium x phosphate product (range, −16.3 to −23.4 mg2/dL2). The mean serum calcium concentration increased in all subgroups except those treated with sevelamer alone (range, +0.3 to +0.5 mg/dL). In contrast, only subjects treated concurrently with vitamin D metabolites experienced a reduction in PTH. Subjects treated with sevelamer alone or sevelamer with calcium without vitamin D experienced an increase in PTH with treatment. Conclusion: Sevelamer hydrochloride is a safe and effective phosphate binder in hemodialysis patients. Sevelamer should be used in combination with vitamin D metabolites to jointly control hyperphosphatemia and hyperparathyroidism. Randomized clinical trials will be required to determine the optimal management strategies for metabolic bone disease in end-stage renal disease, as well as less advanced stages of chronic renal insufficiency.

Efeect of histamine H2-receptor antagonisits on the phosphorus-binding ability of phosphate binders in hemodialysis patients

Efeect of histamine H<SUB>2</SUB>-receptor antagonisits on the phosphorus-binding ability of phosphate binders in hemodialysis patients

Effect of iron as a new type of phosphate binder in hemodialysis patients

Hyperphosphatemia is one of the major problems requiring management in the majority of hemodialysis patients and they require phosphate-binding agents to control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used currently as phosphate-binding agents to treat hyperphosphatemia, but these compounds can cause undesirable side effects. Therefore, the development of new phosphate-binding agents is imperative. It is well known that oral and intravenous administration of iron causes hypophosphatemia. We hypothesized that this side effect of iron may be beneficial for the treatment of hyperphosphatemia in hemodialysis patients. Consequently, we conducted a fundamental and clinical investigation of the effects of iron administration. Membrane permeability of phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium hydroxide in the presence of hydrogenated lecithin as a phosporic compound was examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of sodium ferrous citrate given orally for eight weeks. The permeability of the filtering membrane to phosphorus decreased in accordance with the dosage of sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate-binding effect of sodium ferrous citrate was larger than that of dessicated aluminum hydroxide. Serum phosphorus decreased significantly during the experiment. These results suggest that the oral administration of sodium ferrous citrate as a new phosphate binder is a useful therapeutic method for hemodialysis in patients with hyperphosphatemia.

Calcium carbonate (CaCO3): an efficient and safe phosphate binder in haemodialysis patients? A 3-year study.

In an uncontrolled study, 22 dialysis patients (46 +/- 14 years, duration of dialysis 20 +/- 11 months) were treated with CaCO3 over a period of up to 3 years to lower their serum phosphate. The use of 4.5-9 g CaCO3 daily over a period of 9 months led to a reduction of mean serum phosphate from 2.51 to 1.51 mmol/l in 77% of patients, with a simultaneous increase in mean calcium concentration from 2.23 to 2.47 mmol/l, and an improved control of secondary hyperparathyroidism by reduction in mPTH from 1552 to 1032 pg/ml and in APH activity from 6.25 to 4.55 mumol/s/l. In long-term CaCO3 treatment of up to 3 years, however, a constant effective phosphate reduction could not be achieved. There was a progression (77%) of pre-existing microcalcification and a new appearance (42%) of microcalcification in vessels and soft-tissue areas of the hand. The percentage of patients with soft-tissue calcification increased from 43 to 67% during a treatment period of 3 years. We conclude that CaCO3 alone is not suitable on a long-term basis for phosphate reduction in dialysis patients.

血液透析患者におけるリン吸着剤としての炭酸カルシウム

血液透析患者25例を対象としてリン吸着剤をアルミゲルより炭酸カルシウムに変更して, 12か月にわたり検討した. 当初アルミゲルと同量の炭酸カルシウムを投与し, その後血清Caが11.0mg/dl以下, 血清Pが7.0mg/dl以下になるように, 炭酸カルシウムおよび1α (OH) D3の量を増減した. 20例で炭酸カルシウムのみでリンのコントロールが可能であった. 2例が腹部膨満感のためにアルミゲルのみに移行し, 3例は高リン血症のため, アルミゲルの併用が必要であった. 炭酸カルシウムのみでりンのコントロールが可能であった20例では, 血清アルミニウムは92.4±43.1μg/lより34.3±10.5μg/lまで有意に低下した. また20例中10例で1過性の高Ca血症 (10.8mg/dl以上) が認められたが, 炭酸カルシウム変更後12か月の時点では, 変更前と比較して血清Ca, P, Al-pの値には変化はなかった. 一方血清PTHは前後で有意の増加が認められた.アンケート調査では, 約半数例で炭酸カルシウムはアルミゲルに比べて内服しにくいと答えており, その理由としては, 散剤であるということが多かった. リンのコントロールの不良群に対して, リン制限の指導を行いアルミゲルを中止することができた. 今後このような症例に対して低リン食の指導が必要と考えた.