Control Of Serum Phosphorus Levels Research Articles

Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia

Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels. Therefore, drugs with novel mechanisms of action that can be added to existing PBs to further lower serum phosphorus levels are desired. Tenapanor, a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporters, decreases passive phosphate absorption in the intestine, thereby decreasing serum phosphorus levels. This study evaluated the efficacy and safety of tenapanor treatment with up-titration when added to PBs among Japanese hemodialysis patients with hyperphosphatemia poorly controlled by PBs alone. In total, 169 patients taking PBs whose serum phosphorus level was≥6.1 and<10.0 mg/dl initiated the 8-week treatment (placebo+ PB, n= 85; tenapanor+ PB, n= 84). The least squares mean change from baseline to week 8 in serum phosphorus level was-0.24 and-2.00 mg/dl in the placebo and tenapanor groups, respectively, with a statistically significant difference between groups (-1.76 mg/dl; P< 0.0001). Diarrhea as a treatment-emergent adverse event (TEAE) occurred in 14.1% and 63.1% of patients in the placebo and tenapanor groups, respectively. All diarrhea events were mild or moderate. Tenapanor added to PBs improved serum phosphorus levels that could not previously be controlled by PBs alone, and no new safety concerns were raised.

Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study.

BackgroundThe iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis.MethodsThis non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels.ResultsThe safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: −1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%.ConclusionsSFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.

Clinical Evaluation of the Safety, Efficacy and Tolerability of Lanthanum Carbonate in the Management of Hyperphosphatemia in Patients with End-Stage Renal Disease.

Patients with progressive chronic kidney disease (CKD) commonly develop mineral and bone abnormalities and extraskeletal calcifications with following increased cardiovascular risk. A key pathophysiological role is played by hyperphosphatemia. Since diet and dialysis are often insufficient to control serum phosphorus levels, many patients require treatment with phosphate binders. Among them is lanthanum carbonate, an aluminum-free non-calcium-based compound. The present review summarizes the most recent literature data concerning the safety, efficacy and tolerability of lanthanum carbonate in patients with end-stage renal disease and hyperphosphatemia. The drug is taken orally as chewable tablets or powder with only minimal gastrointestinal absorption and resulting reduced risk of tissue deposition and systemic drug interactions. The dissociation of the drug in the acid environment of the upper gastrointestinal tract induces the release of lanthanum ions, which bind to dietary phosphate forming insoluble complexes then excreted in the feces. Even though there is no clear evidence that lowering serum phosphorus levels can improve patient-centered outcomes, a mortality benefit with all phosphate binders, especially non-calcium containing ones, is not excluded. Lanthanum carbonate has been suggested to decrease all-cause mortality but not cardiovascular event rate compared to other phosphate binders. It induces a lower suppression of bone turnover than calcium carbonate and calcium acetate and may improve systolic function and cardiac dimension compared to calcium carbonate. Moreover, the use of lanthanum carbonate has been associated with better nutritional status compared to other phosphate binders, lower risk for hypercalcemia than calcium-containing binders, and amelioration of mild metabolic acidosis contrary to sevelamer hydrochloride. Main adverse effects include nausea, alkaline gastric reflux, gastric deposition of lanthanum, gastrointestinal obstruction, subileus, ileus, perforation, fecal impaction, and reduction of gastrointestinal absorption of some drugs including statins, angiotensin-converting enzyme inhibitors and some antibiotics such as fluoroquinolones or tetracyclines.

P0927THE IMPACT OF NUTRITIONAL EDUCATION ON PHOSPHORUS CONTROL IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Hyperphosphatemia is frequently encountered in hemodialysis patients and is an important risk factor of cardiovascular diseases. It is usually difficult to be managed by phosphate binders and hemodialysis. This study was carried out to assess the effect of nutritional education (NE) on the control of serum phosphorus level in hemodialysis patients. Method An open label, single center randomized controlled trial was conducted in the nephrology department, New Mansoura General Hospital, Egypt. One hundred hemodialysis patients were randomized into two groups; intervention Group (IG) (n=50) subjected to NE program for 3 months and Control group (CG) (n=50) received the usual care. Nutritional education was applied for the intervention group, by a trained renal dietitian, in the form of educational sessions, booklets, procures, audio visual teaching aids and patient-tailored counselling. Nutritional evaluation was done for all patients using dietary history, 24 hour diet recall sheet and malnutrition inflammation score (MIS) in addition to assessment of anthropometrics measurements and routine laboratory tests before randomization and at the end of the study. Results Three months after randomization, body mass index, waist circumference and midarm muscle circumference (MAMC) were significantly lower among IG versus the CG (p=0.04, 0.04 and 0.004 respectively). MIS score was significantly lower among the IG compared to the CG (p=0.02). Regarding laboratory tests, serum phosphorus level and calcium X phosphorus product were significantly lower among IG compared to the CG at the end of the study (p&amp;lt;0.001 and =0.04 respectively) with a percent change of serum phosphorus of -13.8 ± 21.41 after NE. The percentage of patients with hyperphosphatemia (&amp;gt; 5.5 mg/dl) were significantly lower in the IG at the end of study (p=0.04). Other laboratory tests including serum albumin, hemoglobin level, iron status and urea reduction ratio did not show any significant difference between both groups. Conclusion NE applied to dialysis patients added to the control of hyperphosphaemia without exposing the patients to the risk of malnutrition, resulting from injudicious dietary restrictions.

SAT-266 PHOSPHATE KINETICS IN TWICE PER WEEK HEMODIALYSIS SESSIONS IN INDIAN PATIENTS WITH ENDSTAGE RENAL DISEASE

In patients with endstage renal disease, control of serum phosphorus levels is primarily achieved by a combination of oral phosphate binders and removal by hemodialysis. In India, a majority of patients receive twice per week hemodialysis and previous data on dietary phosphorus intake in Indian dialysis patients is lacking. This study examines phosphate kinetics during twice a week hemodialysis alongwith an assessment of dietary energy, protein and phosphorus intake in an Indian hemodialysis population. The study was conducted at a tertiary care teaching and referral hospital in northern India, and 28 consecutive stable patients (interim analysis of trial CTRI/2019/05/019383) on maintenance hemodialysis for more than 3 months were recruited by August 31, 2019. All the hemodialysis sessions were performed using F7 dialyzers on the Fresenius 4008S ARRT Plus machines (Fresenius Medical Care, Germany), with a dialysate flow rate of 500 ml/minute and a duration of 4 hours, on the first dialysis session of that week (the session preceded by a four day gap). Dietary energy, protein and phosphorus intakes were assessed using 2-day food diary and a validated food frequency questionnaire. Compliance and dosage of phosphate binder therapy was assessed by entries made in the patient-filled diary. Serum phosphorus levels were measured prior to and at hourly intervals till one hour after hemodialysis. Dialytic phosphorus removal was assessed by collection of spent dialysate by partial dialysate collection method. All the data were represented as medians with interquartile range and analysed using SPSS software (v16, IBM Corp, USA). Of the 28 patients, 20 were male, 6 were diabetic and equally from urban and rural areas. Nearly all the patients consumed diets with energy-adjusted phosphorus intake of > 1 g/day. Hyperphosphatemia (serum phosphorus levels were > 5.5 mg/dl) was seen in 32% and secondary hyperparathyroidism (iPTH > 500 pg/ml) was seen in 36% of the study population. Patients with hyperphosphatemia had higher body mass index, mid-arm circumference and dietary protein intake than those with normal serum phosphorus levels (p= 0.02,0.03,0.03 respectively)(Table 1). Hyperphosphatemia was associated with secondary hyperparathyroidism and higher intake of phosphate binders and calcitriol (p= 0.007, 0.01, 0.05, respectively). The median dialytic phosphorus removal during a single session of hemodialysis was 1116 mg/session in the group with hyperphosphatemia and 615 mg/session in those with serum phosphorus < 5.5 mg/dl (p=0.002). In patients with hyperphosphatemia, 76% of fall in serum phosphorus levels occurred in the first one hour of starting hemodialysis, whereas in patients with serum phosphorus<5.5 mg/dl, nearly 100% of fall to post-dialytic levels occurred within the first hour(p=0.002).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Inspite of an overall high phosphorus intake, hyperphosphatemia and secondary hyperparathyroidism were seen in only upto one-third of the study population, possibly due to poorly absorbed vegetarian sources. Higher protein intake, still under 1.2 g/kg body weight contributed to hyperphosphatemia in this setting of twice per week dialysis. As a steep fall in serum phosphorus took place in the first hour, we postulate that increasing the frequency of dialysis would result in better control of serum phosphorus than increasing individual session length.

Application of bioelectrical impedance analysis in nutritional assessment of patients with hemodialysis

Objective To explore the effect and related influencing factors of body composition measurement based on bioelectrical impedance analysis(BIA)in evaluating the nutritional status of patients with maintenance hemodialysis(MHD). Methods A total of 54 patients with MHD were selected as research objects. The nutritional status of MHD patients was evaluated by BIA, anthropometric indexes and laboratory indexes. The related influencing factors of skeletal muscle loss in MHD patients were analyzed by multiple linear regression analysis. Results The results of BIA showed that the incidence of skeletal muscle deficiency was 40.74%, and the detection rate was high. Pearson correlation analysis showed that skeletal muscle was significantly correlated with body mass index, high-density lipoprotein, transferrin, serum phosphorus, body cell volume, bone mineral content, basic metabolism, upper arm muscle circumference, upper arm circumference, body fat percentage, protein and inorganic salt(P<0.05). Multiple linear regression analysis showed that serum phosphorus and protein were the influencing factors of skeletal muscle(P<0.05). Conclusion The incidence of malnutrition in MHD patients is high, and the problem of skeletal muscle reduction is prominent. Serum phosphorus and protein levels are the influencing factors of skeletal muscle content in MHD patients. It is necessary to strengthen the control of serum phosphorus level in patients with MHD in order to slow down the process of skeletal muscle atrophy. BIA technology combined with laboratory index detection is recommended for comprehensive evaluation and regular follow-up of nutritional status of MHD patients.

Duration of Serum Phosphorus Control Associated with Overall Mortality in Patients Undergoing Peritoneal Dialysis

Background: Serum phosphorus (SP) level is closely associated with overall mortality and cardiovascular events, while the role of SP controlled duration is not fully recognized. Here, we conducted a retrospective cohort study in our department to identify the relationship of SP controlled duration with clinical outcomes in patients undergoing peritoneal dialysis (PD). Methods: PD patients in our center from January 1, 2009, to June 30, 2019, were followed up at 2-month (the first year) or 5-month (the next follow-up period) intervals, and until death, until PD withdrawal, or until June 30, 2019. Data at each follow-up point were collected from their medical records. SP levels, changed degree of SP over baseline, and SP controlled duration were analyzed with overall mortality, PD withdrawal (including death, transferred to hemodialysis, and received renal transplantation), and combined endpoint (including death, acute heart failure, cardiovascular event, and stroke). Results: A total of 530 patients entered the analysis. Of them, 456 (86.0%) had hyperphosphatemia before dialysis, and the SP levels decreased soon after dialysis. The degree of SP change over baseline was the maximum at the 3rd month after dialysis (−31.0%), and lower degree was associated with higher overall mortality (hazard ratio [HR], 1.012; 95% CI, 1.004–1.020; p = 0.003). The median SP controlled duration was 13 (5–28) months, and longer duration was significantly associated with lower overall mortality (HR, 0.968; 95% CI, 0.956–0.981; p < 0.001). After categorization, duration more than 12 months greatly improved overall mortality with a HR of 0.197 (0.082–0.458; p < 0.001 vs. SP never controlled group) and 0.329 (0.150–0.724; p = 0.006 vs. duration <12 months group). Longer SP controlled duration also improved PD withdrawal and combined endpoint. Conclusions: In summary, both degree and duration of SP control were tightly associated with overall mortality. We should control SP levels as early, as possible, and as long as we could.

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.

Dietary Phosphate and the Forgotten Kidney Patient: A Critical Need for FDA Regulatory Action

Careful dietary management that reduces high phosphate intake is recommended to slow the progression of chronic kidney disease (CKD) and prevent complications of CKD and may help reduce chronic disease risks such as incident CKD associated with high phosphate intake in the healthy general population. For patients treated with maintenance dialysis, control of serum phosphorus levels is considered a marker of good care and requires a coordinated plan that limits dietary phosphate intake, uses oral phosphate binders, and provides an adequate dialysis prescription. Even with traditional thrice-weekly hemodialysis or peritoneal dialysis, use of phosphate binders, and a concerted effort to limit dietary phosphate intake, adequately controlled serum phosphorus levels are not possible in all dialysis patients. Efforts to limit phosphate intake are thwarted by the underestimated and unquantified phosphate content of processed foods and some medications due to the hidden presence of phosphate additives or excipients added during processing or drug formulation. Effectively limiting phosphate intake could potentially be achieved through simple US Food and Drug Administration regulatory actions. Mandatory labeling of phosphate content on all packaged foods and drugs would enable identification of healthy low-phosphate foods and medications and permit critically important control of total phosphate intake. Simple changes in regulatory policy and labeling are warranted and would enable better management of dietary intake of phosphate at all stages of kidney disease, as well as potentially reduced health risks in the general population.

Effectiveness of sucroferric oxyhydroxide in patients on on-line hemodiafiltration in real-world clinical practice: A retrospective study.

Introduction:Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group.Objective:To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden.Methods:A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO.Results:A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment.Conclusion:During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.

Nutritional Considerations for Dialysis Vegetarian Patients, Part One

Nutritional Considerations for Dialysis Vegetarian Patients, Part One

Pharmacological, pharmaceutical and clinical profiles of sucroferric oxyhydroxide (P-TOL® Chewable Tab. 250 mg, 500 mg), a therapeutic agent for hyperphosphatemia

Sucroferric oxyhydroxide (P-TOL® chewable tablets, 250 and 500 mg) is a phosphate binder for oral use; it is composed of polynuclear iron (III)-oxyhydroxide, sucrose, and starches, and is currently indicated for alleviating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. The results of non-clinical pharmacological studies have suggested that P-TOL consistently decreases serum phosphorus levels in the aqueous environment at pH levels similar to those in the gastrointestinal tract, thereby suppressing the progression of secondary hyperparathyroidism, aberrant calcification, and abnormal bone metabolism associated with hyperphosphatemia. Since the diameter of the P-TOL tablet exceeds 15 mm, it is manufactured with a doughnut-shape to minimize choking hazards. From the results of pharmaceutical studies, it was indicated that the P-TOL tablets promptly disintegrated in the gastrointestinal tract and excessive iron uptake from this product is unlikely to occur. In clinical studies, P-TOL (one tablet/dose, t.i.d.) decreased serum phosphorus levels during treatment Week 1 and allowed stable, long-term control of serum phosphorus levels. Furthermore, P-TOL was expected to reduce the tablet burden on patients and to improve medication adherence. The most common adverse reaction was diarrhea. However, in most cases, the symptoms were mild and oral administration of P-TOL could be continued. Although iron-related parameters tended to increase, iron uptake from this product was low, and the risk of iron overload was considered to be low. These findings confirm the efficacy and safety of P-TOL in CKD patients with hyperphosphatemia. Therefore, sucroferric oxyhydroxide therapy is a potentially useful treatment option for hyperphosphatemia.

Pharmacotherapy in chronic kidney disease hyperphosphatemia – effects on vascular calcification and bone health

Hyperphosphatemia (HP) in patients with chronic kidney disease (CKD) leads to complications such as renal osteodistrophy, cardiovascular calcification and hemodynamic abnormalities, all of them having a serious impact on the survival rate and quality of life. Also, HP is a key pathogenic factor in the development of secondary hyperparathyroidism (SHPT) in CKD. Having in regard the significance of controlling serum phosphorus levels (Pi), in this paper, the needs and obstacles to successful pharmacological management of HP in CKD are presented, with an overview of major classes of phosphate binders (PBs) and other drugs affecting Pi level, such as active vitamin D sterols and calcimimetics (CMs). In addition, their effects on progression of cardiovascular calcification and bone health are elaborated. In this regard, a PubMed search was carried out to capture all abstracts and articles relevant to the topic of CKD, HP and mineral metabolism, bone disorders and vascular/valvular calcification (VC), published from January 2007 to August 2017. The search was limited to English language, with the search terms including drug name AND hyperphosphatemia or cardiovascular calcification or bone disorder. Comparative studies, clinical studies/trials and meta-analyses related to different classes/representatives of PBs, vitamin D analogues and CMs were reviewed and research data related to their efficacy and safety compared. Keywords: chronic kidney disease, hyperphosphatemia, phosphate binders, active vitamin D sterols, calcimimetics, bone disorders, cardiovascular calcification

Real-world effectiveness of sucroferric oxyhydroxide in patients on chronic hemodialysis: A retrospective analysis of pharmacy data .

Aims: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients. Materials and methods: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 – 3) and 6 months (SO 4 – 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed. Results: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 – 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 – 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%). Conclusions: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day.

Psychosocial Factors That Create Barriers to Managing Serum Phosphorus Levels in Pediatric Dialysis Patients: A Retrospective Analysis

Abnormal phosphorus homeostasis is among the medley of metabolic disturbances commonly associated with chronic kidney disease. We sought to determine the psychosocial factors that create barriers to controlling serum phosphorus levels in children on dialysis and to evaluate the perceptions of children and caregivers on the ease or difficulty of following a dietary phosphorus restriction and taking phosphorus binder medications. Single center cross-sectional study. Pediatric dialysis unit at a children's hospital. Forty-eight patients on chronic hemodialysis or peritoneal dialysis (mean age: 11.03±6.88years; 69% male). Serum phosphorus levels were recorded from electronic health records and converted to a mean phosphorus standard deviation score (SDS) for each individual. Mean phosphorus SDS values were compared to each independent categorical variable using an analysis of variance test, continuous variables were analyzed using linear regression, and logistic regression was used to determine odds ratios. There was a significant relationship between age and phosphorus SDS (P<.001), with patients over 13years of age having the highest prevalence of hyperphosphatemia (88%). Patients and caregivers who identified phosphorus levels as "controlled" had lower phosphorus SDS values compared to the other subjects (P=.003). However, of the patients and caregivers who reported that serum phosphorus levels were "controlled," 46% were hyperphosphatemic. Furthermore, 73% and 87% of patients and caregivers reported that following a phosphorus-restricted diet and taking phosphorus binders were "easy"; yet, 40% and 49% of these patients were hyperphosphatemic, respectively. In the present study, elevated serum phosphorus levels were most common in adolescent dialysis patients. There also appears to be a disconnect between the perceived ease of following a phosphorus-restricted diet and taking phosphorus binders and the achievement of normal serum phosphorus levels. These data further emphasize the importance of ongoing education regarding dietary and medical management requirements.

Nocturnal eating disturbs phosphorus excretion in young subjects: a randomized crossover trial.

BackgroundNocturnal eating have recently increased. Serum phosphorus levels and regulators of phosphorus have circadian variations, so it is suggested that the timing of eating may be important in controlling serum phosphorus levels. However, there have been no reports on the effects of nocturnal eating on phosphorus metabolism.The objective was to evaluate the effects of nocturnal eating on phosphorus metabolism.MethodsFourteen healthy men participated in two experimental protocols with differing dinner times. The design of this study was a crossover study. The subjects were served test meals three times (breakfast; 07:30 h, lunch; 12:30 h, dinner; 17:30 or 22:30 h) a day. Blood and urine samples were collected to assess diurnal variation until the following morning.ResultsThe following morning, fasting serum phosphorus levels in the late dinner group were markedly higher than those in the early dinner group (p < 0.001), although serum calcium levels were maintained at approximately constant levels throughout the day in both groups. Fluctuations in urinary calcium excretion were synchronized with the timing of dinner eating, however, fluctuations in urinary phosphorus excretion were not synchronized. Urinary phosphorus excretions at night were inhibited in the late dinner group. In the late dinner group, intact parathyroid hormone levels didn’t decrease, and they were significantly higher in this group compared with the early dinner group at 20:00 h (p = 0.004). The following morning, fasting serum fibroblast growth factor 23 levels in the late dinner group had not changed, but those in the early dinner group were significantly increased (p = 0.003). Serum free fatty acid levels before dinner were significantly higher in the late dinner group compared with the early dinner group.ConclusionsOur results indicate that nocturnal eating inhibits phosphorus excretion. It is suggested that nocturnal eating should be abstained from to manage serum phosphorus levels to within an adequate range.

Randomized, Double-Blind, Placebo-Controlled, Withdrawal Study of Colestilan after Dose Titration in Chronic Kidney Disease Dialysis Patients with Hyperphosphatemia

Background/Aims: Colestilan is a new non-calcium-based phosphate binder licensed in Europe for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis (CKD 5D). This study was conducted to evaluate efficacy in a North American patient population and also to examine secondary actions of colestilan on lipid profile and glycated hemoglobin (HbA1c). Methods: This was a multicenter, randomized, double-blind, placebo-controlled withdrawal study, after an initial open-label titration period. Patients (n = 245) with stable phosphate control received 6-15 g/day colestilan during a 12-week, flexible titration period after which 169 were randomized to continue the same dose (n = 85) or switch to placebo (n = 84) for 4 weeks. The primary endpoint was the change in serum phosphorus level during the placebo-controlled withdrawal period. Results: A significant difference of -1.01 mg/dl (-0.33 mmol/l) in mean change in serum phosphorus, favoring colestilan, was seen during the placebo-controlled withdrawal period (p < 0.001). Colestilan reduced serum phosphorus significantly from baseline to week 12 (-1.54 mg/dl (-0.50 mmol/l); p < 0.001). Serum calcium levels were not affected. Colestilan significantly reduced and maintained reductions in calcium × phosphorus ion product (Ca × P), parathyroid hormone, total cholesterol, low-density lipoprotein cholesterol, uric acid and also HbA1c in patients with elevated baseline HbA1c. Colestilan was generally well tolerated; most adverse events were gastrointestinal. Conclusion: In this first clinical trial with colestilan in a North American patient population, colestilan demonstrated significant efficacy in controlling serum phosphorus levels in CKD 5D patients with hyperphosphatemia, without increasing calcium levels.

Novel iron-based phosphate binders in patients with chronic kidney disease.

Management of hyperphosphatemia remains an integral component in the care of patients with chronic kidney disease on dialysis. In addition to dietary restriction and dialysis, oral phosphate binders remain a key strategy in the control of serum phosphorus levels in this population. We review two new oral phosphate binders that are currently marketed in the United States. Sucroferric oxyhydroxide was approved by the U.S. Food and Drug Administration (FDA) in November 2013. A recent international, multicenter study found the drug to be efficacious and noninferior to sevelamer carbonate in magnitude of serum phosphate control. This was achieved with a significantly reduced daily pill burden for sucroferric oxyhydroxide. A second novel agent, ferric citrate was approved by the FDA in September, 2014. The drug was found to have similar phosphate control efficacy to active comparators and was superior to placebo. In addition, the drug delivers a significant amount of iron, resulting in improved erythropoietic parameters. Both drugs had diarrhea as a fairly frequent side-effect. These new phosphate binders offer alternatives to currently available agents. Both have interesting properties that may make them particularly useful in clinical practice.

Sucroferric oxyhydroxide: a review in hyperphosphataemia in chronic kidney disease patients undergoing dialysis.

Sucroferric oxyhydroxide (Velphoro®), an iron-based oral phosphate binder, is available for the control of serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis. In a pivotal phase III trial, sucroferric oxyhydroxide 1000-3000 mg/day for 24 weeks was noninferior to sevelamer carbonate 4800-14,400 mg/day with regard to lowering serum phosphorus levels. Additionally, sucroferric oxyhydroxide at maintenance dosages was significantly more effective than low dosage sucroferric oxyhydroxide (250 mg/day) with regard to maintaining controlled serum phosphorus levels during weeks 24-27 of treatment. Sucroferric oxyhydroxide had a numerically lower mean daily pill burden and better treatment adherence than sevelamer carbonate. Treatment with sucroferric oxyhydroxide was generally well tolerated over 24 weeks' treatment, with the most frequently reported treatment-emergent adverse events being mild, transient diarrhoea and discoloured faeces. In a 28-week extension study, the efficacy and tolerability profile of sucroferric oxyhydroxide remained similar to sevelamer carbonate for up to 52 weeks. In conclusion, sucroferric oxyhydroxide is a valuable treatment option for hyperphosphataemia in CKD patients on dialysis, providing an effective and generally well tolerated noncalcium-based phosphate binder therapy with a lower pill burden than sevelamer carbonate and the potential for improved treatment adherence.

Tackling non-adherence in dialysis patients with hyperphosphataemia

Many patients with late-stage chronic kidney disease require oral phosphate binders to control serum phosphorus levels. However, non-adherence to phosphate binders remains a major challenge and is affected by a number of factors. Nurses have a pivotal role in the day-to-day management of dialysis patients and are well placed to potentially provide education and information about the importance of treatment adherence. Sucroferric oxyhydroxide is a novel iron-based phosphate binder that has been investigated in clinical studies for the treatment of hyperphosphataemia in dialysis patients, where it has demonstrated similar efficacy to sevelamer carbonate, in terms of reducing serum phosphorus levels, but with a significantly lower pill burden and better treatment adherence. This article reviews key Phase 3 clinical data for sucroferric oxyhydroxide and discusses how the attributes of this new phosphate binder may help to address the challenge of patient adherence to phosphate binders in clinical practice. A lot of patients with end-stage renal disease are prescribed phosphate binders to control serum phosphorus levels and treat hyperphosphataemia. However, many studies have demonstrated that adherence to these drugs is low. Viatcheslav Rakov, Edward Chong and Jennifer Parker present a summary of recent research carried out on a new phosphate binder and challenges to adherence.