The Effect of Niacinamide Supplementation on Phosphate Concentrations in Dutch Dialysis Patients: A Randomized Crossover Trial.

OBJECTIVE: Hyperphosphatemia is a common complication in patients with kidney failure, despite the use of phosphate binders. Vitamin B3, either in the form of niacin or niacinamide (NAM), shows potential as "add-on" treatment to reduce serum phosphate concentrations in this population. NAM seems to lack many of the side effects that are observed with niacin. The aim of this study was to investigate whether NAM is an effective and acceptable treatment in reducing serum phosphate concentrations in patients with kidney failure. METHODS: DiaNia was a double-blind placebo-controlled randomized crossover trial, comparing NAM (250-500 mg/day) to placebo as "add-on" treatment to an individual treatment with approved phosphate binders for 12 weeks in patients receiving hemodialysis. The primary outcome was serum phosphate concentrations, and the secondary outcomes were platelet counts as well as drop-outs due to side effects. Data were analyzed using both per-protocol and intention-to-treat analyses. RESULTS: Mean age of the per-protocol population (n = 26) was 63.6 ± 17.2 years and 53.8% were men. NAM treatment significantly reduced serum phosphate with 0.59 mg/dL (p = .03). Linear mixed-effects models demonstrated superiority of 12 weeks NAM over 12 weeks placebo with a between-treatment difference of 0.77 mg/dL (95% CI 0.010, 1.43; P = .03). Similar results, although not significant, were found in the intention-to-treat population. We found no between-treatment differences in platelet counts and during the NAM treatment we observed 3 drop-outs due to side effects (8.6%). CONCLUSION: NAM is effective in reducing serum phosphate concentrations in patients with kidney failure receiving hemodialysis. In addition, NAM is well-tolerated and seems not to increase the risk of thrombocytopenia. Thus, NAM can be valuable as "add-on" treatment to combat hyperphosphatemia in patients with kidney failure. However, more research in larger populations is needed to confirm this.

Efficacy and Safety of Sucroferric Oxyhydroxide Compared with Sevelamer Carbonate in Chinese Dialysis Patients with Hyperphosphataemia: A Randomised, Open-Label, Multicentre, 12-Week Phase III Study.

INTRODUCTION: This study aimed to investigate the efficacy and safety of sucroferric oxyhydroxide (SFOH) versus sevelamer carbonate in controlling serum phosphorus (sP) in adult Chinese dialysis patients with hyperphosphataemia (sP >1.78 mmol/L). METHODS: Open-label, randomised (1:1), active-controlled, parallel group, multicentre, phase III study of SFOH and sevelamer at starting doses corresponding to 1,500 mg iron/day and 2.4 g/day, respectively, with 8-week dose titration and 4-week maintenance (NCT03644264). Primary endpoint was non-inferiority analysis of change in sP from baseline to week 12. Secondary endpoints included sP over time and safety. RESULTS: 415 patients were screened; 286 were enrolled and randomised (142 and 144 to SFOH and sevelamer, respectively). Mean (SD) baseline sP: 2.38 (0.57) and 2.38 (0.52) mmol/L, respectively. Mean (SD) change in sP from baseline to week 12: - 0.71 (0.60) versus -0.63 (0.52) mmol/L, respectively; difference (sevelamer minus SFOH) in least squares means (95% CI): 0.08 mmol/L (-0.02, 0.18) with the lower limit of 95% CI above the non-inferiority margin of -0.34 mmol/L. The SFOH group achieved target sP (1.13-1.78 mmol/L) earlier than the sevelamer group (56.5% vs. 32.8% at week 4) and with a lower pill burden (mean 3.7 vs. 9.1 tablets/day over 4 weeks of maintenance, respectively). Safety and tolerability of SFOH was consistent with previous studies, and no new safety signals were observed. CONCLUSION: SFOH effectively reduced sP from baseline and was non-inferior to sevelamer after 12 weeks of treatment but had a lower pill burden in Chinese dialysis patients with hyperphosphataemia; SFOH benefit-risk profile is favourable in Chinese patients.

Biochemical markers of iron status and iron accumulation in peritoneal dialysis patients treated with ferric citrate.

BACKGROUND: Hyperphosphataemia is a common complication of kidney disease. Current dialysis techniques do not provide enough phosphorus clearance, hence the need to use phosphorus binders. Treatment options include calcium carbonate, calcium acetate, lanthanum carbonate, sevelamer hydrochloride and iron-based binders. Patients receiving peritoneal dialysis (PD) with sustained elevated ferritin levels exceeding 800 ng/mL are at a higher risk of death. We identify PD patients treated with iron-based binders and compare ferritin and risk of iron accumulation to patients treated with non-iron-based binders. METHODS: All records of patients receiving PD at Emory dialysis centres until 30 October 2021 were reviewed for phosphorus binders. Basic demographics and laboratory data were time-referenced to the days on treatment with a particular binder. Patients were followed until discontinuation of the phosphorus binder, death, transplant, transfer to another dialysis provider or censoring at 36 months after medication was started. RESULTS: Compared to calcium acetate and sevelamer, ferric citrate utilisation in PD patients resulted in a sustained increase in ferritin. The proportion of patients with a ferritin equal to or greater than 800 ng/dL and transferrin saturation greater than 40% increased over time in patients treated with ferric citrate and was higher during the second and third year of follow-up compared to baseline values and to patients treated with calcium acetate or sevelamer. Two patients (7%) treated with ferric citrate developed clinically significant haemosiderosis. CONCLUSIONS: Use of ferric citrated in PD resulted in significant iron accumulation as judged by ferritin levels.

Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial.

BACKGROUND: Tenapanor is a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis. METHODS: This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5-7.0 mg/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint. RESULTS: Of the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was - 1.18 mg/dL (95% confidence interval: - 1.54, - 0.81 mg/dL) with tenapanor. From a baseline value of 7.65 mg/dL, serum phosphorus decreased to 6.14 and 5.44 mg/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5-6.0 mg/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%. CONCLUSIONS: Administration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable. TRIAL REGISTRATION: NCT04766385.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

Family-centered empowerment approach to optimize phosphate management among hemodialysis patients: an experimental study.

BACKGROUND: This study aimed to investigate the effect of a family-centered empowerment program on hyperphosphatemia management. METHOD: This experimental study was performed on 80 randomly selected eligible patients with hyperphosphatemia undergoing hemodialysis. Patients were assigned randomly to two groups of family-centered empowerment program (FCEPG) and control group (CG) by coin toss (40 people per group). Data collection tools were the researcher-made Phosphate Control Knowledge Scale, the researcher-made Adherence to Dietary Restriction of Phosphorus Intake Scale, the eight-item Morisky Medication Adherence Scale, and serum phosphorus measurements. Data were collected before the intervention, one month, and three months after the intervention. Patients in FCEPG participated in a family-centered empowerment program. The statistical significance level was considered to be 0.05. RESULTS: Inter-group comparisons showed no significant difference between FCEPG and CG in terms of the mean score of knowledge of phosphate control, adherence to dietary restriction of phosphorus intake, adherence to medication, and the mean serum phosphorus level before the empowerment program, but showed significant differences between them in these respects at one month after the program and three months after the program (p < 0.05). Intra-group comparisons showed a significant difference in FCEPG between the mean and standard deviation of all four variables before the empowerment program and the corresponding values one month and three months after the program (P < 0.05). CONCLUSION: The findings of this study can be used in various fields of healthcare in the hospital and community.

Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We performed a meta-analysis of randomized placebo-controlled trials to evaluate the efficacy and safety of tenapanor. METHODS: All randomized controlled trials of tenapanor were searched up to 1 August 2022. The primary endpoint was the change in serum phosphorus level from baseline with tenapanor and placebo. Data on drug-related adverse events (AEs), gastrointestinal AEs and diarrhea were collected to determine the safety of tenapanor. RESULTS: There were 533 patients throughout five trials that were eligible. Tenapanor significantly lowered blood phosphorus level by 1.79 mg/dl in the mean difference than the placebo. Diarrhea, gastrointestinal AEs, and drug-related AEs were more severe than placebo. CONCLUSIONS: This meta-analysis showed that although drug side effects were common, tenapanor significantly reduced serum phosphorus level in hemodialysis patients.

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series.

The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention's role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy-substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders' initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives-in particularized diets adapted to each patient's comorbidities-and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants' age.

Patiromer Treatment in Patients With CKD, Hyperkalemia, and Hyperphosphatemia: A Post Hoc Analysis of 3 Clinical Trials.

RATIONALE & OBJECTIVE: Patients with chronic kidney disease (CKD), hyperkalemia (serum potassium [sK+]>5.0 mEq/L), and hyperphosphatemia experience poor clinical outcomes. Patiromer, a potassium binder that uses calcium as the exchange ion, may also reduce serum phosphorus (sP). We characterized the effect of patiromer on sP in patients with CKD, hyperkalemia, and hyperphosphatemia. STUDY DESIGN: A post hoc pooled analysis of individual-level data from the AMETHYST-DN, OPAL-HK, and TOURMALINE trials of patiromer. SETTING & PARTICIPANTS: Patients with CKD and hyperkalemia. EXPOSURE: Patients treated with patiromer (8.4-33.6 g/day). OUTCOME: Mean changes from baseline in sP, sK+, serum calcium (sCa2+), and serum magnesium (sMg2+) after 2 and 4 weeks of treatment. ANALYTICAL APPROACH: Descriptive statistics to summarize pooled data on the study outcomes from the 3 studies. RESULTS: We included 578 patients in the analysis. Of these participants, 86 patients (14.9%) had baseline hyperphosphatemia of whom 75.6% (65 of 86) had CKD stage 4/5 and 31.1% (153 of 492) with sP≤4.5mg/dL had CKD stage 4/5. Among the patients with elevated sP and sK+at baseline, the mean±SD reduction in sP and sK+after 4 weeks of patiromer treatment was-0.62±1.09mg/dL and-0.71± 0.51 mEq/L, respectively. Additionally, the mean±SD reduction in sMg2+in these patients was -0.25±0.23mg/dL while sCa2+remained unchanged. Both sMg2+and sCa2+remained within the normal range. Patiromer was generally well tolerated, and no serious adverse events were considered related to patiromer. LIMITATIONS: These were post hoc analyses, no placebo comparison was performed due to the design of the original studies, and the follow-up period was limited to 4 weeks. CONCLUSIONS: Reductions in sP and sK+to the normal range were observed after 2 weeks of patiromer treatment, and the reduction was sustained during 4 weeks of treatment among patients with non-dialysis-dependent CKD, hyperkalemia, and hyperphosphatemia. Future controlled trials are needed to establish if patiromer is useful to reduce both sK+and sP in hyperkalemic patients with CKD and hyperphosphatemia.

New Directions in Phosphorus Management in Dialysis.

Current phosphate management strategies in end-stage renal disease (dietary phosphate restriction, dialysis, and phosphate binders) are inadequate to maintain target phosphate levels in most patients. Dietary phosphate restriction is challenging due to "hidden phosphates" in processed foods, and dialysis and phosphate binders are insufficient to match average dietary phosphate intake. As phosphate binders must be taken with each meal, patients need to ingest many, large pills several times a day, negatively impacting quality of life. Recent advances in our understanding of phosphate absorption pathways have led to the development of new nonbinder therapies that block phosphate absorption. This review describes the limitations of current phosphate management strategies and discusses new therapies in development that inhibit phosphate absorption pathways. These new therapies present an opportunity to rethink phosphate management, potentially by prescribing phosphate absorption inhibitors as a primary therapy and adding phosphate binders if needed.

A real-world analysis of the influence of age on maintenance hemodialysis patients: managing serum phosphorus with sucroferric oxyhydroxide as part of routine clinical care.

OBJECTIVE: Despite the growing number of elderly hemodialysis patients, the influence of age on nutritional parameters, serum phosphorus (sP), and use of phosphate-binder (PB) medications has not been well characterized. We aimed to describe age-related differences in patient characteristics in a large, real-world cohort of maintenance hemodialysis patients, and to examine the impact of age on sP management with sucroferric oxyhydroxide (SO). METHODS: We retrospectively analyzed de-identified data from 2017 adult, in-center hemodialysis patients who switched from another PB to SO monotherapy as part of routine clinical care. Changes in baseline PB pill burden, sP levels, and nutritional and dialytic clearance parameters were assessed across varying age groups through 6 months. RESULTS: At baseline, older patients had lower mean sP, serum albumin, and pre-dialysis weights compared with younger patients. Prescription of SO was associated with a 62% increase in the proportion of patients achieving sP ≤ 5.5 mg/dl and a 42% reduction in daily pill burden. The proportion of patients achieving sP ≤ 5.5 mg/dl after transitioning to SO increased by 113, 96, 68, 77, 61, 37 and 40% among those aged 19-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years, respectively. CONCLUSIONS: Older patients had worse nutritional parameters, lower pill burden, and lower sP at baseline versus younger counterparts. Prescription of SO was associated with improved sP control and reduced pill burden across all ages.

Effect of low-dose lanthanum carbonate on calcium and phosphorus metabolism in Asian Patients with end-stage renal disease, maintenance hemodialysis and hyperphosphatemia.

Objective: This study aimed to examine whether a 12-week small-dose lanthanum carbonate (LaCO3; 500 mg/d) treatment could improve calcium and phosphorus metabolism and parathyroid function in Asian patients with end-stage renal disease (ESRD) under hemodialysis. Methods: This was a prospective observational study of patients treated at our Hospital between 10/2014 and 02/2015. The patients were given 500 mg/d of LaCO3 with lunch for 12 weeks. Results: Baseline and after 12-week treatment serum phosphorus levels were 2.49±0.51 mmol/L and 1.65±0.34 mmol/L (P<0.001). The baseline and after 12-week treatment calcium×phosphorus product were 69.40±17.34 mg2/dL2 and 44.27±9.67 mg2/dL2 (P<0.001). There was no significant difference in serum calcium and iPTH levels from baseline to after 12 weeks treatment (both P>0.05). Fourteen (25.9%) patients developed gastrointestinal adverse reactions to LaCO3 and 10 patients improved after treatment. Conclusion: Far below the 1.5-3.0g/d required by the drug instructions, LaCO3 500 mg/d for 12 weeks can still reduce serum phosphorus level and calcium × phosphorus product, without serum calcium and iPTH levels increase.

Hyperphosphatemia during nutrition recovery in patients with severe anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a disorder associated with many medical complications. Regarding phosphorus metabolism, the only recognized alteration is hypophosphatemia associated with refeeding syndrome. However, in our clinical practice, we have observed a high frequency of hyperphosphatemia in late phases of nutrition therapy in severely undernourished AN patients, which has barely been described. MATERIALS AND METHODS: We carried out a retrospective study of patients with AN hospitalized for severe decompensation of the disease. RESULTS: Eleven patients were included, all women, with a median age of 23 years [20-46] and a body mass index at admission of 12.2 kg/m2 [11.7-13.1]. Hyperphosphatemia was noted in 9 of the 11 cases (81.8%) with a median time to onset of 53 days [30-75]. The median peak serum phosphorus (P) level was 5.1 mg/dl [4.9-5.4]. An inverse relationship was found between the increase in P levels and phosphorus supplementation at the onset of admission. The magnitude of the P increase was associated with the body weight gain achieved during nutrition therapy. CONCLUSION: Late hyperphosphatemia during nutrition therapy in severely undernourished AN patients affects more than 80% of cases. Body weight gain throughout nutrition therapy is a predictor of increased P levels.

Evaluation of cerium oxide as a phosphate binder using 5/6 nephrectomy model rat.

BACKGROUND: The number of chronic kidney disease (CKD) patients continues to increase worldwide. CKD patients need to take phosphate binders to manage serum phosphorus concentrations. Currently, several types of phosphate binder, including lanthanum carbonate, are used. However, they each have disadvantages. METHODS: In this study, we evaluated cerium oxide as a new phosphate binder in vitro and in vivo. First, cerium oxide was mixed with phosphoric acid at pH 2.5 or 7.0, and residual phosphoric acid was measured by absorption photometry using colorimetric reagent. Second, cerium oxide was fed to 5/6 nephrectomy model rats (5/6Nx), a well-known renal damage model. All rats were measured food intake, water intake, feces volume, and urine volume, and collected serum and urine were analyzed for biochemical markers. RESULTS: Cerium oxide can adsorb phosphate at acidic and neutral pH, while lanthanum carbonate, which is a one of popular phosphate binder, does not dissolve at neutral pH. Cerium oxide-treatment reduced serum phosphate concentrations of 5/6Nx rats without an increase in serum alanine transaminase levels that would indicate hepatotoxicity, and cerium oxide-treatment maintained serum creatinine and blood urea nitrogen levels, while those of normal 5/6Nx rats increased slightly. CONCLUSIONS: These results suggest that cerium oxide can be a potential phosphate binder. Decreased body weight gain and increased water intake and urine volume in 5/6Nx rats were thought to be an effect of nephrectomy because these changes did not occur in sham operation rats. Additional investigations are needed to evaluate the longer-term safety and possible accumulation of cerium oxide in the body.

A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

Sodium phosphate cotransporter 2a inhibitors: potential therapeutic uses.

PURPOSE OF REVIEW: Targeting sodium phosphate cotransporter 2a (Npt2a) offers a novel strategy for treating hyperphosphatemia in chronic kidney disease (CKD). Here we review recent studies on the efficacy of Npt2a inhibition, its plasma phosphate (Pi)-lowering effects, as well as potential "off-target" beneficial effects on cardiovascular consequences. RECENT FINDINGS: Two novel Npt2a-selective inhibitors (PF-06869206 and BAY-767) have been developed. Pharmacological Npt2a inhibition shows a significant phosphaturic effect and consequently lowers plasma Pi and parathyroid hormone (PTH) levels regardless of CKD. However, plasma fibroblast growth factor 23 (FGF23), a master regulator of Pi homeostasis, shows inconsistent responses between these two inhibitors (no effect by PF-06869206 vs. reduction by BAY-767). In addition to the effects on Pi homeostasis, Npt2a inhibition also enhances urinary excretions of Na+, Cl-, and Ca2+, which is recapitulated in animal models with reduced kidney function. The effect of Npt2a inhibition by BAY-767 on vascular calcification has been studied, with positive results showing that oral treatment with BAY-767 (10 mg kg-1) attenuated the increases in plasma Pi and Ca2+ content in the aorta under the setting of vascular calcification induced by a pan-FGF receptor inhibitor. Together, Npt2a inhibition offers a promising therapeutic approach for treating hyperphosphatemia and reducing cardiovascular complications in CKD. SUMMARY: Npt2a inhibition significantly increases urinary Pi excretion and lowers plasma Pi and PTH levels; moreover, it exerts pleiotropic "off-target" effects, providing a novel treatment for hyperphosphatemia and exhibiting beneficial potential for cardiovascular complications in CKD.

Phosphate balance during dialysis and after kidney transplantation in patients with chronic kidney disease.

PURPOSE OF REVIEW: In patients with chronic kidney disease (CKD), hyperphosphatemia is associated with several adverse outcomes, including bone fragility and progression of kidney and cardiovascular disease. However, there is a knowledge gap regarding phosphate balance in CKD. This review explores its current state, depending on the stage of CKD, dialysis modalities, and the influence of kidney transplantation. RECENT FINDINGS: Adequate phosphate control is one of the goals of treatment for CKD-mineral and bone disorder. However, ongoing studies are challenging the benefits of phosphate-lowering treatment. Nevertheless, the current therapy is based on dietary restriction, phosphate binders, and optimal removal by dialysis. In the face of limited adherence, due to the high pill burden, adjuvant options are under investigation. The recent discovery that intestinal absorption of phosphate is mostly paracellular when the intraluminal concentration is adequate might help explain why phosphate is still well absorbed in CKD, despite the lower levels of calcitriol. SUMMARY: Future studies could confirm the benefits of phosphate control. Greater understanding of the complex distribution of phosphate among the body compartments will help us define a better therapeutic strategy in patients with CKD.

The effect of egg white diet on phosphorus control in dialysis patients.

INTRODUCTION: Nutritional interventions have been envisaged to improve hyperphosphatemia and malnutrition, two important risk factors associated with mortality in dialysis patients. We evaluated the effects of egg white consumption on serum phosphate and malnutrition in dialysis patients. METHODS: In an open-label, per protocol clinical trial, conducted in Kerman dialysis centers, 150 hemodialysis patients aged ≥18 years with serum phosphorus ≥5.5 mg/dl were included in the study. All participants limited their intake of foods containing phosphorus for 4 weeks, and then they were divided into a control and an intervention group. The control group continued their ordinary diet and the participants in the intervention group consumed a Telavang egg white pack (containing six egg whites, 96 calories, 24 g protein) as a substitute for meat products 3 days a week for 8 weeks. Finally, changes in serum albumin, phosphorus, calcium, PTH, and cholesterol were measured. FINDINGS: At the baseline, there were no significant differences in the laboratory variables between the two groups. After 8 weeks, serum cholesterol (124.3 ± 38.1, vs. 135.8 ± 28.8, p = 0.003) and phosphorus levels (4.5 ± 1.03, vs. 6.7 ± 1.5, p = 0.001) were significantly lower in the intervention group compared with the control group. Also, serum albumin (4.5 ± 0.07 vs. 3.7 ± 0.4, p = 0.001) was significantly higher in the intervention group. Moreover, phosphorus, PTH, and cholesterol levels in the intervention group were significantly lower than their baseline values (p = 0.001). CONCLUSION: The results showed that the egg white could be a useful source of protein for dialysis patients, as it simultaneously reduces serum phosphorus and cholesterol, and increases serum albumin.

Safety and effectiveness of ferric citrate hydrate in serum phosphorus management of patients with chronic kidney disease: a long-term, real-world, observational, post-marketing surveillance study.

BACKGROUND: Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD). This post-marketing surveillance study was performed to investigate the long-term safety and effectiveness of FC. METHODS: This prospective, multicenter, observational post-marketing surveillance study was performed in a real-world setting in Japan. The study involved CKD patients with hyperphosphatemia receiving FC who were undergoing either hemodialysis or peritoneal dialysis or were non-dialysis-dependent. Adverse drug reactions, iron- and erythrocyte-related parameters (i.e., levels of serum ferritin, transferrin saturation, and hemoglobin), and serum levels of phosphorus, corrected calcium, and intact parathyroid hormone were monitored for up to 104 weeks. RESULTS: Safety was evaluated in 2723 patients. Of these patients, 20.5% discontinued FC because of adverse events, and 3.9% discontinued FC because of unsatisfactory effectiveness. Iron-related parameters gradually increased after the initiation of FC treatment but stabilized after week 36. Effectiveness was analyzed in 2367 patients. Serum phosphorus immediately decreased, and the effect persisted for 104 weeks. CONCLUSION: In this 104 week surveillance study, no new safety concerns were noted. The safety profile was not obviously different from those in pre-approval clinical trials and the 52 week interim report of this surveillance study. The serum ferritin level of most patients was below the upper limit of the target range, and iron overload risk was not evident. Long-term FC treatment effectively controlled serum phosphorus.