Tenapanor improves long-term control of high phosphate concentrations in the blood in patients receiving maintenance dialysis: a plain language summary of the NORMALIZE study.

What is this summary about?This is a summary of an article that was published in the medical journal Kidney360 describing results from the NORMALIZE study. The NORMALIZE study looked at how well tenapanor tablets reduced higher-than-normal levels of phosphate in the blood of persons with kidney disease who are on maintenance dialysis. These persons are unable to keep their blood phosphate levels in a normal range, and high levels of phosphate can contribute to several serious health consequences.Tenapanor is approved as an add-on treatment for high levels of phosphate in the blood of adults with chronic kidney disease who are on maintenance dialysis and whose disease does not respond adequately to treatment with phosphate binders or who are not able to take phosphate binders. In earlier clinical studies, tenapanor was studied alone or studied together with phosphate binders. In a 1-year clinical study called PHREEDOM, researchers learned that when tenapanor was used alone, it lowered blood phosphate levels, and treated patients experienced acceptable safety and tolerability as determined by the doctors running the study. In the NORMALIZE study, adult patients took a 30-mg tenapanor tablet twice a day, either alone or with sevelamer, for up to 18 months after they completed the PHREEDOM study.What were the main conclusions reported by the researchers?The researchers found that one-third of patients taking tenapanor, either alone or with sevelamer, achieved normal blood phosphate levels. This is an improvement from the current standard of care with sevelamer alone to reduce blood phosphate levels. As seen in the earlier studies of tenapanor, the most common adverse event experienced by patients was softer or loose stools. No new safety concerns were reported in the NORMALIZE study.What are the key takeaways?The researchers concluded that tenapanor, used alone or combined with sevelamer, can be used long-term by adult patients receiving maintenance dialysis to reduce the phosphate levels in their blood to within the normal range. Patients who take tenapanor may experience softer or loose stools.This summary was developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and/or caregivers, better understand the effects of taking tenapanor.[Box: see text]Link to original article here.

Effectiveness of tenapanor for treating hyperphosphatemia in patients receiving dialysis: a plain language summary of the OPTIMIZE study.

What is this summary about?This summary provides a review of the OPTIMIZE study, the results of which were published in Kidney360 in February 2024. The OPTIMIZE study looked at how well tenapanor tablets work to treat patients receiving dialysis who have high levels of phosphate in their blood, a condition called hyperphosphatemia. In the OPTIMIZE study, researchers wanted to understand if tenapanor would decrease phosphate levels in the blood to the target range. They also tested different ways of starting tenapanor treatment in patients.In the human body, kidneys are organs that filter blood and remove waste products. In chronic kidney disease, sometimes referred to as CKD, a patient's kidneys do not work as well at filtering their blood and removing waste products. This can allow phosphate to build up in the blood. Phosphate levels may remain high despite patients receiving treatment such as dialysis, using pills that keep phosphate in the intestines (called phosphate binders) to prevent phosphate from being absorbed into the blood, and eating a low-phosphate diet. Phosphate levels may remain high despite these treatments because they can be difficult to follow. Most people receiving dialysis take 7­8 phosphate binder pills every day, and over half of those people have reported skipping at least one dose in the past month. Additionally, low-phosphate diets can be difficult to follow and people often struggle to meet their other nutritional needs.What are the key takeaways?Tenapanor used in combination with phosphate binders led to lower phosphate levels in the blood with the use of fewer phosphate-lowering pills. Tenapanor also lowered phosphate levels in patients who were not previously on phosphate binders but needed phosphate-lowering treatment.What were the main conclusions reported by the researchers?Tenapanor can help patients receiving dialysis better control their hyperphosphatemia.[Box: see text]Link to original article here.

Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.

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.

Novel genetic mutation associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome treated with denosumab: a case report.

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.

The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.

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.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

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.

Tolerability, safety and efficacy of a novel phosphate binder VS-505 (AP301): a Phase 2 dose-escalation and dose-ranging study in patients undergoing maintenance hemodialysis.

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. CLINICAL TRIAL REGISTRATION NUMBER: NCT04551300 .

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.

Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis.

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.

Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.

Hyperphosphatemia is a common feature in patients with impaired kidney function and is associated with increased risk of cardiovascular disease. This phenomenon extends to the general population, whereby elevations of serum phosphate within the normal range increase risk; however, the mechanism by which this occurs is multifaceted, and many aspects are poorly understood. Less than 1% of total body phosphate is found in the circulation and extracellular space, and its regulation involves multiple organ cross talk and hormones to coordinate absorption from the small intestine and excretion by the kidneys. For phosphate to be regulated, it must be sensed. While mostly enigmatic, various phosphate sensors have been elucidated in recent years. Phosphate in the circulation can be buffered, either through regulated exchange between extracellular and cellular spaces or through chelation by circulating proteins (ie, fetuin-A) to form calciprotein particles, which in themselves serve a function for bulk mineral transport and signaling. Either through direct signaling or through mediators like hormones, calciprotein particles, or calcifying extracellular vesicles, phosphate can induce various cardiovascular disease pathologies: most notably, ectopic cardiovascular calcification but also left ventricular hypertrophy, as well as bone and kidney diseases, which then propagate phosphate dysregulation further. Therapies targeting phosphate have mostly focused on intestinal binding, of which appreciation and understanding of paracellular transport has greatly advanced the field. However, pharmacotherapies that target cardiovascular consequences of phosphate directly, such as vascular calcification, are still an area of great unmet medical need.

Elevated luminal inorganic phosphate suppresses intestinal Zn absorption in 5/6 nephrectomized rats.

Zinc (Zn) is an essential trace element in various biological processes. Chronic kidney disease (CKD) often leads to hypozincemia, resulting in further progression of CKD. In CKD, intestinal Zn absorption, the main regulator of systemic Zn metabolism, is often impaired; however, the mechanism underlying Zn malabsorption remains unclear. Here, we evaluated intestinal Zn absorption capacity in a rat model of CKD induced by 5/6 nephrectomy (5/6 Nx). Rats were given Zn and the incremental area under the plasma Zn concentration-time curve (iAUC) was measured as well as the expression of ZIP4, an intestinal Zn transporter. We found that 5/6 Nx rats showed lower iAUC than sham-operated rats, but expression of ZIP4 protein was upregulated. We therefore focused on other Zn absorption regulators to explore the mechanism by which Zn absorption was substantially decreased. Because some phosphate compounds inhibit Zn absorption by coprecipitation and hyperphosphatemia is a common symptom in advanced CKD, we measured inorganic phosphate (Pi) levels. Pi was elevated in not only serum but also the intestinal lumen of 5/6 Nx rats. Furthermore, intestinal intraluminal Pi administration decreased the iAUC in a dose-dependent manner in normal rats. In vitro, increased Pi concentration decreased Zn solubility under physiological conditions. Furthermore, dietary Pi restriction ameliorated hypozincemia in 5/6 Nx rats. We conclude that hyperphosphatemia or excess Pi intake is a factor in Zn malabsorption and hypozincemia in CKD. Appropriate management of hyperphosphatemia will be useful for prevention and treatment of hypozincemia in patients with CKD.NEW & NOTEWORTHY We demonstrated that elevated intestinal luminal Pi concentration can suppress intestinal Zn absorption activity without decreasing the expression of the associated Zn transporter. Increased intestinal luminal Pi led to the formation of an insoluble complex with Zn while dietary Pi restriction or administration of a Pi binder ameliorated hypozincemia in chronic kidney disease model rats. Therefore, modulation of dietary Pi by Pi restriction or a Pi binder might be useful for the treatment of hypozincemia and hyperphosphatemia.

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.

Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis.

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 < 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 < 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 < 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.

Health Economic Benefits of Introducing Sucroferric Oxyhydroxide in the Treatment of Patients with Chronic Kidney Disease under Dialysis in the Kingdom of Saudi Arabia.

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.

A 47-Year-Old Man with Hyperphosphatemia Due to Chronic Renal Failure Treated with Lanthanum Carbonate Tablets Presenting Acutely with Partial Large Bowel Obstruction.

BACKGROUND Hyperphosphatemia is a complication of chronic renal failure (CRF) due to reduction in the glomerular filtration rate. Lanthanum carbonate is a commonly used phosphate binder for patients with CRF and hyperphosphatemia, but has adverse effects if patients are not monitored. This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. The incidence of lanthanum carbonate causing intestinal obstruction is rare, and few cases in the literature have described the course of the disease in detail. CASE REPORT A 47-year-old man diagnosed with diabetic nephropathy underwent hemodialysis treatment and was prescribed 0.5 g/day of chewable lanthanum carbonate tablets. After taking lanthanum carbonate for 5 months, the patient experienced symptoms of decreased bowel movements and exhaustion, which progressively worsened. Abdominal computed tomography (CT) revealed multiple hyperdensities in the large bowel, indicating the presence of lanthanum deposition. Lanthanum carbonate was promptly discontinued. After undergoing enema and catharsis treatment, the large bowel obstruction was relieved, and the hyperdensities in the abdominal CT disappeared. The colonoscopy and histologic examination revealed ulcerations and inflammatory changes in the large bowel mucosa. CONCLUSIONS This report highlights the rare association between the use of lanthanum carbonate tablets and intestinal obstruction. Healthcare providers should enhance their vigilance regarding lanthanum carbonate-induced serious gastrointestinal adverse reactions and actively seek to detect lanthanum deposition by abdominal CT or radiography (X-ray). After the occurrence of lanthanum deposition, drug withdrawal and promotion of defecation are primary treatment methods.

Long-term safety and decrease of pill burden by tenapanor therapy: a phase 3 open-label study in hemodialysis patients with hyperphosphatemia.

Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption. Tenapanor is a novel drug administered as a small tablet, twice daily. This multicenter, open-label, single-arm, phase 3 study aimed to evaluate the long-term safety of tenapanor and its efficacy in decreasing PB pill burden. Tenapanor 5 mg twice daily was administered to hemodialysis patients with serum phosphorus level 3.5-7.0 mg/dl at baseline; the dose could be increased up to 30 mg twice daily. Patients could also switch from PBs. The primary endpoint was safety during 52-week administration. The key secondary endpoint was a ≥ 30% reduction in the total pill number of daily PBs and tenapanor from baseline. Of 212 patients starting treatment, 154 completed the study. Diarrhea was the most frequent adverse event, occurring in 135 patients (63.7%); most events were classified as mild (74.8%). No clinically significant changes occurred other than serum phosphorus level. At Week 52/discontinuation, 158/204 patients (77.5%) achieved the key secondary endpoint. Complete switching from PBs to tenapanor was achieved in 50-76 patients (26.7%-41.5%), and 80 patients (51.9%) at Week 8-12 and Week 50, respectively. Serum phosphorus remained generally stable within the target range (3.5-6.0 mg/dl). These findings suggest the long-term safety and tolerability of tenapanor. Tenapanor could reduce or eliminate PB pill burden while controlling serum phosphorus levels.Trial registration: NCT04771780.