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Objective: In 2017, our Level IV NICU switched from providing bovine-derived (BOV-fort) to human milk-derived fortifiers (HM-fort) and donor human milk (DHM) to premature infants born ≤ 30 weeks or ≤1250 g. Following this change, providers anecdotally observed increased hypoglycemia, hypercalcemia, and hyperphosphatemia. This study investigated potential laboratory differences between infants fed Bovine vs. Human milk derived fortifier., Methods: Lab measurements from 402 infants (232 BOV-fort, 170 HM-fort) born between 2015 and 2019 were compared between groups., Results: The proportion of infants ever having a blood glucose ≤ 45 mg/dL (p < 0.0001) was higher in the HM-fort group. The proportion of infants ever experiencing a phosphorus > 8.0 mg/dL were higher in the HM-fort group (p < 0.0001). The proportion of infants ever experiencing calcium > 11.4 mg/dL was higher in the HM-Fort group (p = 0.019)., Conclusions: Provision of HM-Fort and DHM to extremely premature infants is associated with metabolic derangements., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Phosphorus is a macroelement found in the body, mostly in the bones as crystals of hydroxyapatite. Higher levels are found in patients affected by chronic kidney disease (CKD). Since the early stage of CKD phosphorous excretion is impaired, but the increase of PTH and FGF23 maintains its level in the normal range. In the last decades, the role of FGF23 in erythropoiesis was studied, and now it is well known for its role in anemia genesis in patients affected by conservative CKD. Both Hyperphosphatemia and anemia are two manifestations of CKD, but many studies showed a direct association between serum phosphorous and anemia. Phosphorus can be considered as the common point of more pathogenetic ways, independent of renal function: the overproduction of FGF23, the worsening of vascular disease, and the toxic impairment of erythropoiesis, including the induction of hemolysis., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Introduction: The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear., Methods: The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching., Results: The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period., Conclusion: Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Excessive dietary phosphorus is a concern among patients with kidney failure undergoing dialysis treatment because it may contribute to hyperparathyroidism and hyperphosphatemia. A long-standing but untested component of the low-phosphorus diet is the promotion of refined grains over whole grains. This paper reviews the scientific premise for restricting whole grains in the dialysis population and estimates phosphorus exposure from grain products based on three grain intake patterns modeled from reported intakes in the general US population, adjusting for the presence of phosphorus additives and phosphorus bioavailability: (1) standard grain intake, (2) 100% refined grain intake, and (3) mixed (50/50 whole and refined grain) intake. Although estimated phosphorus exposure from grains was higher with the mixed grain pattern (231 mg/day) compared to the 100% refined grain pattern (127 mg/day), the amount of additional phosphorus from grains was relatively low. Given the lack of strong evidence for restricting whole grains in people with CKD, as well as the potential health benefits of whole grains, clinical trials are warranted to address the efficacy and health impact of this practice., (© 2024 Wiley Periodicals LLC.)

Background: Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are common obstacles to assessing phosphorus balance and controlling phosphorus in hemodialysis patients. We aimed to investigate whether individualized therapy using a phosphorus balance calculator improves phosphorus control., Methods: A randomized, open-label, multicenter, 4-week clinical trial was conducted. A total of 119 maintenance hemodialysis patients aged 18-85 years old and with serum phosphorus level >1.45 mmol/L from three university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n = 60) or conventional therapy (n = 59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment., Results: Among 119 randomized participants [mean age 62 years; 68 male (57%)], 116 completed the trial. Using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state and significantly reduced serum phosphorus (1.62 ± 0.45 mmol/L versus 1.85 ± 0.45 mmol/L, P = .006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P = .006) and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (-0.47 versus -0.23 mmol/L, P = .010) when compared with conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, or the adjusted mean difference of serum calcium and PTH levels over the treatment period., Conclusion: Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.

Background: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care., Methods: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment., Results: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up)., Conclusions: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden., (© 2024. The Author(s).)

Introduction: Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics., Methods: This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model., Results: 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant., Conclusion: Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study., Competing Interests: SD received honoraria and travel grants from Kyowa Kirin, Sanofi and Dr Reddy’s. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Disthabanchong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dialytic phosphate removal is a cornerstone of the management of hyperphosphatemia in peritoneal dialysis (PD) patients, but the influencing factors on peritoneal phosphate clearance (PPC) are incompletely understood. Our objective was to explore clinically relevant factors associated with PPC in patients with different PD modality and peritoneal transport status and the association of PPC with mortality., Methods: This is a cross-sectional and prospective observational study. Four hundred eighty-five PD patients were enrolled and divided into 2 groups according to PPC. All-cause mortality was evaluated after followed-up for at least 3 months., Results: High PPC group showed lower mortality compared with Low PPC group by Kaplan-Meier analysis and log-rank test. Both multivariate linear regression and multivariate logistic regression revealed that high transport status, total effluent dialysate volume per day, continuous ambulatory PD (CAPD), and protein in total effluent dialysate volume appeared to be positively correlated with PPC; body mass index (BMI) and the normalized protein equivalent of total nitrogen appearance (nPNA) were negatively correlated with PPC. Besides PD modality and membrane transport status, total effluent dialysate volume showed a strong relationship with PPC, but the correlation differed among PD modalities., Conclusions: Higher PPC was associated with lower all-cause mortality risk in PD patients. Higher PPC correlated with CAPD modality, fast transport status, higher effluent dialysate volume and protein content, and with lower BMI and nPNA., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023. The Author(s).)

Introduction: Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association., Methods: Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (vs. non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups., Results: Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91-1.06) or all-cause mortality (220 vs. 224 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.93-1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization., Conclusion: Among patients requiring hemodialysis, sevelamer (vs. non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization., (© 2024 S. Karger AG, Basel.)

Phosphate is indispensable for human life and evolutionary changes over several millions of years have established tightly regulated mechanisms to ensure phosphate homeostasis. In this process, calcium and phosphate metabolism have come to be intricately linked together. Three hormones (PTH, FGF23 and Calcitriol) maintain the fine balance of calcium and phosphate metabolism through their actions at three sites (the gut, the kidneys and the skeleton). Disorders that disrupt this balance can have serious clinical consequences. Acute changes in serum phosphate levels can result in life threatening complications like respiratory failure and cardiac arrythmias. Chronic hypophosphataemia predominantly affects the musculoskeletal system and presents as impaired linear growth, rickets, osteomalacia and dental problems. Hyperphosphataemia is very common in the setting of chronic kidney disease and can be difficult to manage. A thorough understanding of calcium and phosphate homeostasis is essential to diagnose and treat conditions associated with hypo and hyperphosphataemia. In this review, we will discuss the calcium and phosphate metabolism, aetiologies and management of hypo and hyperphosphataemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (© 2023 S. Karger AG, Basel.)

Introduction: Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis., Methods: We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year., Results: The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p &lt; 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p &lt; 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p &lt; 0.0001 vs. baseline)., Conclusions: Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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 &gt;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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo, calcium carbonate (CC), or lanthanum carbonate (LC). The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched for articles published through 18 June 2022. The quality of relevant studies was independently analyzed by two investigators who also extracted data from these manuscripts as per Cochrane Collaboration Handbook 5.3. The safety and efficacy of sevelamer as a treatment for hyperphosphatemia in CKD patients were then examined through a meta-analysis, with the primary patient-level outcomes of interest in this analysis being all-cause mortality and the incidence of gastrointestinal adverse effects. Vascular calcification score was also examined as an intermediate outcome, while serum biochemical parameters including levels of phosphate (P), calcium (Ca), intact parathyroid hormone (iPTH), lipids, C-reactive protein (CRP), or fibroblast growth factor-23 (FGF-23) were additionally assessed. In total, this meta-analysis incorporated data from 34 randomized controlled trials (RCTs) enrolling 2802 patients. Sevelamer was associated with reduced all-cause mortality (RR 0.28, CI 0.19 - 0.41, very low certainty ) and Vessel calcification score (RR -0.58, CI -1.11 to -0.04, low certainty ) and induced less hypercalcemia (MD -0.28, CI 0.40 to -0.16, low certainty ) and hyperphosphatemia (MD -0.22, CI -0.32 to -0.13, low certainty ) when compared with Ca-based binders in CKD5D individuals. No significant differences in gastrointestinal adverse events (GAEs) incidence were observed. These data suggest that sevelamer may represent a beneficial means of protecting CKD patients against death and vessel calcification when used to treat hyperphosphatemia, while we found no clinically important benefits in decreasing gastrointestinal adverse effects.

Sevelamer hydrochloride (SH) and calcium carbonate (CaCO 3 ) are two agents included in the phosphate-binding group which are frequently prescribed in the treatment of patients with hyperphosphatemia. However, there are no satisfactory studies on the genotoxic effects of SH in vitro. This study was conducted to reveal the genotoxic and/or cytotoxic potential of these two drugs in cultured human peripheral lymphocytes. Human peripheral lymphocytes were treated with SH and CaCO 3 at sublethal concentrations for 24 or 48 h for micronucleus assay and 1 h in the comet assay. CaCO 3 and SH stimulated a slight increase in micronucleus formation however this increase was not significant compared to the control group. According to the findings of the comet test, only one concentration of the SH caused significant DNA damage (2 mg/ml, 48 h) whereas CaCO 3 did not cause important DNA breakage. No significant oxidative damage or anti-radical effect caused by test substances was observed on the pure pBR322 plasmid DNA in a cell-free medium. Also, it was found that the drugs were devoid of mutagenic activity in the Ames test, but had a weak cytotoxic effect. Both test substances, particularly SH, significantly reduced the nuclear division index compared to the control group. In conclusion, the cytotoxic effect of SH was evident on the basis of in vitro tests and slightly higher than CaCO 3 .

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., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into "iron-based", "only non-iron-based", and "no use". The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate., (© 2023. Springer Nature Limited.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Among the clinical and metabolic complications of progressive chronic kidney disease (CKD), CKD-mineral bone disorder (CKD-MBD) significantly contributes to morbidity and mortality. While overt and persistent hyperphosphatemia is typical of advanced CKD and requires treatment, other abnormalities of calcium/phosphate metabolism begin to occur since the early stages of the disease., Areas Covered: We searched on the PubMed database, without restrictions for language or time range, for randomized clinical trials and meta-analyses investigating phosphate-lowering therapies. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. The in-depth knowledge of the characteristics of these drugs is crucial to ensure adequate treatment to CKD patients., Expert Opinion: A proper control of serum phosphate can be achieved using phosphate binders. These medications may induce side effects. Moreover, data on their impact on clinical outcomes are partly controversial or scarce, especially for the new generation drugs. Hyperphosphatemia favors cardiovascular disease and increases the risk for CKD progression. These effects are partially mediated by fibroblast growth factor 23 (FGF23), a phosphaturic hormone that raises to maintain normal serum phosphate. Since there are no data supporting the use of phosphate-lowering agents when phosphataemia is normal, a key role is played by reducing dietary phosphate intake with the aim to control serum phosphate and the compensatory FGF23 and parathyroid hormone (PTH) increase.

Hyperphosphatemia is a common complication in advanced chronic kidney disease and contributes to cardiovascular morbidity and mortality. The present narrative review focuses on the management of phosphatemia in uremic patients receiving peritoneal dialysis. These patients frequently develop hyperphosphatemia since phosphate anion behaves as a middle-size molecule despite its low molecular weight. Accordingly, patient transporter characteristics and peritoneal dialysis modalities and prescriptions remarkably influence serum phosphate control. Given that phosphate peritoneal removal is often insufficient, especially in lower transporters, patients are often prescribed phosphate binders whose use in peritoneal dialysis is primarily based on clinical trials conducted in hemodialysis because very few studies have been performed solely in peritoneal dialysis populations. A crucial role in phosphate control among peritoneal dialysis patients is played by diet, which must help in reducing phosphorous intake while preventing malnutrition. Moreover, residual renal function, which is preserved in most peritoneal dialysis patients, significantly contributes to maintaining phosphate balance. The inadequate serum phosphate control observed in many patients on peritoneal dialysis highlights the need for large and well-designed clinical trials including exclusively peritoneal dialysis patients to evaluate the effects of a multiple therapeutic approach on serum phosphate control and on hard clinical outcomes in this high-risk population.

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 sMg 2+ in these patients was -0.25±0.23mg/dL while sCa 2+ remained unchanged. Both sMg 2+ and sCa 2+ 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment., Methods: NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250-1500 mg/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders., Results: In the intention-to-treat population (NAMR: n = 539; placebo: n = 183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40 ± 1.55 versus 5.79 ± 1.37 mg/dl, P < .001) with a mean difference of -0.39 mg/dl [95% confidence interval (CI) -0.66 to -0.13], but was comparable between the groups at week 52 [mean difference -0.08 (95% CI -0.36-0.20)]. In the completer population (n = 358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR., Conclusions: NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

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.

Hyperphosphatemia is an electrolyte disorder highly prevalent in patients with chronic kidney disease undergoing hemodialysis (HD) that usually requires treatment with oral phosphate binders (PBs). Sucroferric oxyhydroxide (SO) is a calcium-free, iron-based PB indicated for the control of serum phosphorus. In the real-world setting, SO has shown clinical effectiveness with a lower pill burden and has also been associated with reduced hospital admission rates. This study aims to assess the potential economic benefits resulting from the introduction of SO to the health-care setting of the Kingdom of Saudi Arabia (KSA). An economic analysis using data from a retrospective real-world study that compared HD patients with uninterrupted SO prescriptions with patients who discontinued SO and switched to other PBs (oPBs). Annual drug costs for the estimated PB-eligible population in KSA were quantified. Costs per responder were estimated for all treatments. Hospital admissions' incidence rates were converted into annual inpatient cost savings and were deducted from drug costs to estimate the annual economic effect of SO versus oPBs. Sensitivity and breakeven analyses were also conducted. The eligible population for PB therapy in KSA was estimated at n = 14,748. Treating therapy-eligible populations exclusively with SO was estimated to generate annual inpatient cost-savings of SAR 107.4-119.4 million compared to treating the population with oPBs. The estimated economic effect signified overall annual savings ranging from SAR 82.8 to SAR 94.8 million when the population is treated with SO. Sensitivity analyses showed persistent cost savings. The estimated benefit-cost ratios showed that for every SAR 1 spent on SO, the expected return on investment was SAR 4.4-4.9. SO is an effective therapy that may result in substantial cost savings from reducing hospital admission costs that are attributable to hyperphosphatemia among HD patients., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Hyperphosphatemia is a well-known complication of kidney disease. Phosphate binders are a mainstay treatment, but despite the existence of several phosphate binders, there is no one best approach to manage hyperphosphatemia. Phosphate binders are calcium-based, non-calcium- based, and others. While calcium-based phosphate binders are used frequently, they may cause hypercalcemia. Conversely, lanthanum carbonate and sevelamer were not linked to hypercalcemia but are costlier. The most recently developed class of phosphate binders is the ironbased ferric citrate and sucroferric oxyhydroxide. These have an important role in controlling phosphate levels due to their ability to lower the phosphate while concurrently providing iron sources. This review provides pharmacological profiles of different phosphate binders and their clinical usages, and further elaborates on their place in hyperphosphatemia management., Competing Interests: The authors reported no actual or potential conflict of interest in relation to this nursing continuing professional development (NCPD) activity., (Copyright© by the American Nephrology Nurses Association.)

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., (© 2022. The Author(s).)

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 &gt; 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., (© 2023 S. Karger AG, Basel.)

Background: A key focus for chronic kidney disease management is phosphate control, but currently available binders have suboptimal phosphate-binding capacity, and their characteristics result in low adherence and poor phosphate regulation. Oxylanthanum carbonate, a novel compound that uses proprietary nanoparticle technology to deliver lanthanum, has the potential to combine high phosphate-binding capacity with good intake convenience, thus improving adherence and patient quality of life. The goal of this study was to assess the volume of oxylanthanum Carbonate required to bind 1 g of phosphate and compare it with other currently available phosphate binders to determine which binder allows for the highest normalized potency with the lowest daily medication volume., Methods: Six phosphate binders were assessed: ferric citrate, calcium acetate, lanthanum carbonate, sevelamer carbonate, sucroferric oxyhydroxide, and oxylanthanum carbonate. Table volume measurements were taken using fluid displacement in corn oil or water. Mean daily dose volume to bind 1 g of phosphate was calculated as volume per tablet multiplied by the mean number of tablets taken per day. Volume to bind 1 g of phosphate was calculated by dividing the volume per tablet by its in vivo binding capacity., Results: Oxylanthanum carbonate had the lowest mean volume, daily phosphate binder dose volume, and equivalent phosphate-binding dose volume (volume to bind 1 g of phosphate for each binder)., Conclusions: Oxylanthanum carbonate has the lowest daily phosphate binder dose volume and the smallest volume required to bind 1 g of phosphate compared to all other commercially available phosphate binders. A randomized trial that compares gastrointestinal tolerability across binders would be warranted to demonstrate acceptability and adherence in the target population., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperphosphatemia in patients with renal failure is associated with increased vascular calcification and mortality. Hemodialysis is a conventional treatment for patients with hyperphosphatemia. Phosphate kinetics during hemodialysis may be described by a diffusion process and modeled by ordinary differential equations. We propose a Bayesian model approach for estimating patient-specific parameters for phosphate kinetics during hemodialysis. The Bayesian approach allows us to both analyze the full parameter space using uncertainty quantification and to compare two types of hemodialysis treatments, the conventional single-pass and the novel multiple-pass treatment. We validate and test our models on synthetic and real data. The results show limited identifiability of the model parameters when only single-pass data are available, and that the Bayesian model greatly reduces the relative standard deviation compared to existing estimates. Moreover, the analysis of the Bayesian models reveal improved estimates with reduced uncertainty when considering consecutive sessions and multiple-pass treatment compared to single-pass treatment.

Introduction: For patients with chronic kidney disease (CKD), the need for phosphate binder (PB) treatment peaks at onset of dialysis. This real-world study assessed rates of PB utilization and switching in patients with dialysis-dependent CKD (DD-CKD)., Methods: We identified patients with PB utilization among those with prevalent DD-CKD using 2018-2019 Medicare Parts A/B/D data. Patients were assigned to cohorts based on primary (most frequently used) PB among calcium acetate, ferric citrate, lanthanum carbonate, sevelamer (hydrochloride and carbonate), sucroferric oxyhydroxide. We measured proportion of patients who were adherent (proportion of days covered &gt;80%) and persistent (patients whose last 90 days of outpatient dialysis reported PB use). Net switching rates were calculated as the difference between switches to and from the primary agent., Results: We identified 136,912 patients with PB use. Proportion of patients adherent ranged from 63.8% (lanthanum carbonate) to 67.7% (sevelamer) and persistent from 85.1% (calcium acetate) to 89.5% (ferric citrate). Most patients (73%) used the same PB throughout the study. Overall, 20.5% of patients experienced one switch and 2.3% two or more. Positive net switching rates were observed for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate (2-10%) but negative for sevelamer and calcium acetate (-2% to -7%)., Conclusion: Adherence and persistence rates were low with slight variation across PBs. Net positive switching occurred for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate. Further studies are needed to determine the reasons for these findings and could identify opportunities for better control of phosphate levels among patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Coronary artery calcification (CAC) is predictive of cardiovascular events. We assessed whether a non-calcium-based phosphate binder, lanthanum carbonate (LC), could delay CAC progression compared with a calcium-based phosphate binder, calcium carbonate (CC), in hemodialysis patients., Methods: This was a subsidiary of the LANDMARK study, which is a multicenter, open-label, randomized control study comparing LC and CC for cardiovascular events among Japanese hemodialysis patients with hyperphosphatemia who were at risk of vascular calcification. Participants were randomly assigned (1:1) to receive LC or CC. The changes in the total Agatston score of CAC 2 years from baseline were the primary outcome. Secondary outcomes included the changes in the total Agatston score at 1 year from baseline and the changes in serum phosphate, corrected calcium, and intact parathyroid hormone concentrations., Results: Of 239 patients, 123 comprised the full analysis set. The median daily drug dose (mg) was 750 [interquartile range (IQR), 750‒1500] in the LC group and 3000 (IQR, 3000‒3000) in the CC group; it remained constant throughout the study period. There was no significant difference in the change in total Agatston score from baseline to 2 years between the LC and CC groups [368 (95% confidence interval, 57-680) in the LC group vs. 611 (105-1118) in the CC group; difference, 243 (- 352-838)]., Conclusions: LC-based treatment for hyperphosphatemia did not delay CAC for 2 years compared with CC-based treatment in hemodialysis patients with at least one risk factor for vascular calcification., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Hyperphosphatemia and anemia, which are common complications of chronic kidney disease (CKD), can independently contribute to cardiovascular events. Several previous studies have found that the iron-based phosphate binder, ferric citrate (FC), could be beneficial to both hyperphosphatemia and anemia., Methods: Relevant literature from PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CCRCT) and MEDLINE databases were searched up to 21 February 2022, in order to conduct a meta-analysis to investigate the efficacy, safety and economic benefits of ferric citrate treatment in CKD patients with hyperphosphatemia and anemia. The meta-analysis was conducted independently by two reviewers using the RevMan software (version 5.3)., Results: In total, this study included 16 randomized clinical trials (RCT) involving 1754 participants. The meta-analysis showed that ferric citrate could significantly reduce the serum phosphorus in CKD patients compared to the placebo control groups (MD -1.76 mg/dL, 95% CI (-2.78, -0.75); p  = 0.0007). In contrast, the difference between ferric citrate treatment and active controls, such as non-iron-based phosphate binders, sevelamer, calcium carbonate, lanthanum carbonate and sodium ferrous citrate, was not statistically significant (MD - 0.09 mg/dL, 95% CI (-0.35, 0.17); p  = 0.51). However, ferric citrate could effectively improve hemoglobin levels when compared to the active drug (MD 0.43 g/dL, 95% CI (0.04, 0.82); p  = 0.03) and placebo groups (MD 0.39 g/dL, 95% CI (0.04, 0.73); p  = 0.03). According to eight studies, ferric citrate was found to be cost-effective treatment in comparison to control drugs. Most of the adverse events (AE) following ferric citrate treatment were mild at most., Conclusion: Collectively, our review suggests that iron-based phosphate binder, ferric citrate is an effective and safe treatment option for CKD patients with hyperphosphatemia and anemia. More importantly, this alternative treatment may also less expensive. Nevertheless, more scientific studies are warranted to validate our findings.

Chronic kidney disease-mineral and bone disorders (CKD-MBD) is a common complication of CKD Stages 3-5. Hyperphosphatemia is one of the major metabolic components of CKD-MBD, frequently resulting in vascular calcification (VC) in advanced-stage patients. Also, a long duration of renal replacement therapy can cause the worsening of VC, leading to increased cardiovascular morbidity and mortality. Vascular smooth muscle cells play an important role in the development of VC through osteochondrogenic transformation and the apoptotic process. It has been shown that mitochondrial dysfunction is involved with CKD progression, and excessive oxidative stress can aggravate osteoblastic transformation and VC. Currently, novel interventions targeting mitochondrial function and dynamics, in addition to mitochondrial antioxidants, have been studied with the aim of attenuating VC. This review aims to comprehensively summarize and discuss the experimental and clinical reports concerning mitochondrial studies, along with the purpose of interventions that can improve the outcomes of VC among CKD patients., (© 2022 Wiley Periodicals LLC.)

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/m 2 [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., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Inhibition of intestinal sodium-dependent phosphate transport protein 2b (NaPi2b), responsible for intestinal phosphate absorption, is considered to reduce serum phosphate levels, making it a promising therapeutic approach for hyperphosphatemia. Previously, we aimed to identify new drugs for hyperphosphatemia treatment and obtained zwitterionic compound 3 (IC 50  = 64 nM) as a potent selective inhibitor of intestinal NaPi2b. This small-molecule compound is gut-restricted owing to its almost membrane-impermeable property. However, when compound 3, containing an acylhydrazone structure, is exposed to plasma, it is easily metabolized and likely produces an acetylhydrazine compound. Clinical studies have shown that acetylhydrazine is a risk factor for hepatic toxicity owing to its microsomal metabolism, wherein toxic reactive intermediates are formed. Therefore, in this study, we aimed to obtain potent NaPi2b inhibitors without an acylhydrazone structure to reduce the risk of hepatic toxicity. We developed compound 18, an anilide compound with zwitterionic property having potent phosphate uptake inhibitory activity in vitro (IC 50  = 14 nM) and low bioavailability (FaFg = 5.9%). Oral administration of compound 18 in rats showed a reduction in phosphate absorption comparable to that observed with lanthanum carbonate, a clinically effective phosphate binder used in hyperphosphatemia treatment. Moreover, combined administration of compound 18 and lanthanum carbonate resulted in an additive effect on phosphate absorption inhibition in rats. Our findings suggest that combination therapy with lanthanum carbonate and compound 18 will not only provide better treatment outcomes for hyperphosphatemia but also reduce gastrointestinal side effects in patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022 International Society for Hemodialysis.)