Search

Background Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. Methods We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. Results The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2–treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2–treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. Conclusion In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Introduction Hyperphosphatemia is a common complication as chronic kidney disease (CKD) progresses and most patients undergoing dialysis are prescribed oral phosphate binder therapy to control serum phosphate concentrations. Sucroferric oxyhydroxide is an iron-based phosphate binder approved for the treatment of hyperphosphatemia in CKD patients on dialysis. Areas covered This article reviews key safety and effectiveness data for sucroferric oxyhydroxide from both prospective clinical trials and real-world observational studies. Expert opinion Sucroferric oxyhydroxide potently binds dietary phosphate in the gastrointestinal (GI) tract, resulting in effective reduction of serum phosphate concentrations with a relatively low daily pill burden. Data from clinical trials and real-world observational studies show sucroferric oxyhydroxide has a favorable safety and tolerability profile. The most frequent side effects observed with sucroferric oxyhydroxide are GI-related, mainly discolored (black) stools and mild or moderate transient diarrhea, both of which are manageable. There is minimal systemic iron absorption from sucroferric oxyhydroxide, and therefore the drug is associated with a low risk of iron accumulation. Sucroferric oxyhydroxide also displays low potential for drug-drug interactions with other commonly prescribed oral medications. Overall, sucroferric oxyhydroxide offers an effective and well-tolerated treatment option for the management of hyperphosphatemia.

Based on the use of the determined curing agent (a mixture of electromolten magnesium sand powder and microsilicon powder), an optimized modified phosphate adhesive component and process are proposed. Orthogonal test determined that the modified phosphate binder composition ratio is phosphoric acid:aluminum hydroxide:water:boric acid:citric acid:1% malic acid aqueous solution:triethanolamine = 300:60:80:4:1:5:5. In a laboratory environment of 40% RH × 25 °C, when the amount of binder added is 3.0% (accounting for sand) and the amount of curing agent added is 0.9% (accounting for sand), the 4 h tensile strength of the sample is 0.75 MPa, 24 h the tensile strength reaches 1.21 MPa. The gas volume of the sand sample (600 °C × 3 min) is 6.40 mL g−1, and the high temperature residual strength of the sand sample (600 °C × 5 min) is 0.01 MPa. The modified phosphate binder has higher tensile strength, lower gas evolution and good collapsibility. The binder can meet general casting production requirements.

BACKGROUND: Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. METHODS: In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0–10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set. RESULTS: Of 564 eligible participants randomized to receive tenapanor (n=423) or sevelamer carbonate (n=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (n=128) or placebo (n=127) during the randomized withdrawal period. In the efficacy analysis set (n=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was −1.4 mg/dl (P

Introduction The current management of hyperphosphatemia with phosphate binders is associated with insufficient phosphorus control and a significant pill burden. Tenapanor, a first-in-class, phosphate absorption inhibitor, is expected to control phosphorus and decrease pill burden because of its small pill size and twice daily dosing regimen. This study evaluated tenapanor effectiveness on reducing the phosphate binder pill burden during a 26-week treatment period in Japanese hemodialysis patients. Methods In this multicenter, open-label, single-arm study, hemodialysis patients whose serum phosphorus level was 3.5 to 7.0 mg/dl received tenapanor 30 mg twice daily orally added to their phosphate binder regimen. The phosphate binder dosage was adjusted to achieve a serum phosphorus level within the baseline range of ±0.5 mg/dl. The primary end point was the percentage of patients who achieved a ≥30% decrease in the number of phosphate binders and tenapanor tablets prescribed daily compared with the number of phosphate binder tablets at baseline. Results Of the 67 patients enrolled, 43 completed the study. At baseline, the mean total number of phosphate binder tablets per day was 14.7, which decreased to 3.0 tablets per day at week 26. The primary end point was achieved in 71.6% of patients (P < 0.001). The phosphate binder was completely switched to tenapanor in 28.4% of patients (P < 0.001). The mean phosphorus levels were relatively well controlled (5.19 and 4.71 mg/dl at baseline and week 26, respectively). The most frequent drug-related adverse event (AE) was diarrhea (74.6%). Conclusion Tenapanor provided effective phosphorus control and decreased the number of phosphate binder tablets. The management of drug-related diarrhea will facilitate more widespread use of tenapanor., Graphical abstract

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic ''fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action—tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders—is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis. METHODS: This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5–10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4. RESULTS: Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (−0.84 versus −0.19 mg/dl, P

This is a meta-analysis of randomized controlled trials (RCTs) investigating the effects of oral vitamin D supplementation on serum fibroblast growth factor-23 (FGF23) concentrations in patients with chronic kidney disease (CKD). Manuscripts were extracted from PubMed/MEDLINE, Scopus, and ISI Web of Science through February 2020. Subgroup analyses, sensitivity analysis, and meta-regression assessments were performed. A total of eight clinical trials with nine treatment arms were included in the final analysis. The pooled results showed no significant changes in circulating FGF23 following vitamin D supplementation compared to the control group (Standardized mean difference (SMD): 0.24; 95% confidence intervals (CIs): -0.03 to 0.50, p > 0.05). Subgroup analyses found that studies which had participants with a body mass index (BMI) higher than 25 kg/m2 , with an intervention duration shorter than 15 weeks, using phosphate binder medications, and trials that were on both patients with CKD undergoing hemodialysis and patients without hemodialysis treatment produced significant increases in FGF23 when concentration compared with the control group. This meta-analysis provides evidence that vitamin D supplementation does not have a significant effect on plasma FGF23 levels. However, further high-quality trials are required to identify the influence of oral vitamin D supplementation on FGF23 levels in patients with CKD.

The heightened fibroblast growth factor 23 (FGF23) level in patients with chronic kidney disease (CKD) is associated with increased cardiovascular disease and mortality. We performed a systematic review and meta-analysis to synthesize the available strategies to reduce FGF23 in CKD patients. We conducted a meta-analysis by searching the databases of MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) and single-arm studies that examined the effects of dietary phosphate restriction, phosphate binders, iron supplements, calcimimetics, parathyroidectomy, dialysis techniques, and the outcome of preservation of residual renal function (RRF) on FGF23 levels in CKD patients. Random-effects model meta-analyses were used to compute changes in the outcome of interests. A total of 41 articles (7590 patients), comprising 36 RCTs, 5 prospective studies were included in this meta-analysis. Dietary phosphate restriction less than 800 mg per day yielded insignificant effect on FGF23 reduction. Interestingly sevelamer, lanthanum, iron-based phosphate binders, and iron supplement significantly lowered FGF23 levels. In CKD patients with secondary hyperparathyroidism, calcimimetics prescription could significantly reduce FGF23 levels, while surgical parathyroidectomy had no significant effect. In dialysis patients, preservation of RRF and hemoperfusion as well as hemodiafiltration provided a significant decrease in FGF23 levels. The present meta-analysis demonstrated that non-calcium-based phosphate binders including sevelamer, lanthanum, and iron-based phosphate binders, iron supplements, calcimimetics, hemoperfusion, and preservation of RRF could effectively reduce FGF23 in CKD patients.

In France, long nocturnal dialyses, eight hours three-times a week, are sparsely proposed. However, numerous studies reported that this specific type of dialysis is associated to better blood pressure control, better cardiac remodeling, better mineral and nutritional balance as well as better life quality and survival rate. MATERIAL AND METHODS: In this study, we aimed at quantifying the benefits, risks and obstacles of developing night dialysis and at describing the results of a program that took place in Rennes from 2002 to 2019. Data were collected between 2008 and 2014 for eighteen case-patients and were compared to thirty-six controls that underwent conventional dialysis. Patients were paired according sex, age and year of dialysis start. RESULTS: The median age for dialysis start was 47.5 years [27-60] with a male prevalence (5/1). After six months, a significant difference was reported for postdialytic, systolic and diastolic pressure (respectively 126±15 vs 139±21 [P=0.04] and 72±9 vs 81±14 [P=0.02]) despite an antihypertensive reduction ranging from 2.4±1.4 to 1.3±0.9 per day at six months and 0.7±0.9 at one year (P=0.02). An increase of nPCR was evidenced at 6 and 9 months (P=0.02). At the end of the study, the phosphate level was maintained for both cohorts at the expense of an increased consumption of phosphate binder for the long nocturnal dialysis group (P=0.025). As a whole, 61% of the patients that pursued long night dialysis maintained a professional activity compared to only 30% for the controls (P=0.04). This highlights the advantages of night dialysis for maintaining employment but also the bias that represents the employment status in observational study on this specific topic.

This paper has developed a new compound curing agent powder for a modified phosphate binder (3 wt% of raw sand). This combination can be self-cured and achieve relatively high bonding strength. The optimal composition ratio of curing agent powder is fused magnesia powder:silica fume:sodium polyacrylate at a ratio of 6:6:5, respectively. In this case, the tensile strength of phosphate binder sand sample at 4 h and 24 h is 0.65 MPa and 1.27 MPa, respectively. Infrared spectroscopy and scanning electron microscopy were utilized to analyze the variation of functional groups and the morphology of bonding bridge fracture of phosphate bonded sand samples after the addition of curing agent (fused magnesia powder, silica fume and sodium polyacrylate). The result shows that fused magnesia powder, silica fume and sodium polyacrylate all participate in the polymerization and curing reaction of phosphate binder; furthermore, sodium polyacrylate can effectively mitigate the propagation of cracks on bonding film.

The sintering kinetics of periclase with brucite-aluminum phosphate binder was studied. A model that takes into account the role of the physical compaction and chemical binding in the presence of a binder during the heating process was used to determine the kinetic parameters. The strength of a conglomerate was due to the sintering itself as well as the action of the binder. The effective energy of activation of the sintering of periclase was determined: Ea = 287 ± 9 kJ/mole, which is close to the activation energy of oxygen diffusion in MgO. Spinel MgAl2O4, which slows the sintering process, forms in the material at high temperatures.

Phosphate binders are among the most common medications prescribed to patients with kidney failure receiving dialysis and are often used in advanced chronic kidney disease (CKD). In patients with CKD glomerular filtration rate category 3a (G3a) or worse, including those with kidney failure who are receiving dialysis, clinical practice guidelines suggest "lowering elevated phosphate levels towards the normal range" with possible strategies including dietary phosphate restriction or use of binders. Additionally, guidelines suggest restricting the use of oral elemental calcium often contained in phosphate binders. Nutrition guidelines in CKD suggest

Introduction: Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. Methods: This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. Results: In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; p < 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. Discussion/Conclusion: Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.

For many industries, further progress is possible provided that more efficient refractories of new types are created. The refractory concretes bonded by calcium aluminate phosphate binders in comparison with conventional refractories continue to gain in popularity because of the following advantages: quick installation and low construction costs; reduced and simplified furnace maintenance; good thermal-shock resistance; monolithic (no joints); linings of the units done need not be cured to develop initial strength. The longevity of refractory is essentially increasing provided structure is forming under conditions of the service site. That is why developing of new refractory materials must be carried out by means of its structure design. These principles have been realizing in the refractory concretes technology under the limited conditions of refractory lining installation and industrial unit final heat up. The present paper identifies the phosphate phases responsible for developing mechanical-strength properties of high alumina concretes bonded with calcium aluminate phosphate binders. It sets out the colloid and crystalline phases resulted from interphase interaction that provides the basis for calcium aluminate phosphate binders (suspensions) useful to the refractory industry. The concretes obtained retain their volume integrity after 30 cycles of heating and cooling; can be used for refractory applications > 1700 °С; exhibit sufficient strength of lining 40 MPa.

BackgroundThe iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients.MethodsDe-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1−Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH).Results1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77–1.69 mmol/L during Q1–Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2–62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0–5.3 pills/day during Q1–Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1–2.8 pills/day).ConclusionIn this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Background Etelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety and efficacy of replacing cinacalcet with etelcalcetide in HD patients. Methods One hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively. Results Of the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (p < 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients, p = 0.087; 90 patients, p < 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed. Conclusions This study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet. Trial registration UMIN, UMIN000027637; Registered on June 5, 2017.

Graphical Abstract, Background Calcification propensity is associated with the risk for cardiovascular events and death in end-stage renal disease patients. Here we investigated the effect of lowering serum phosphate with oral phosphate binder therapy on calcification propensity. Methods We performed an open-label, randomized, controlled, crossover study in chronic haemodialysis patients with hyperphosphataemia. Patients (n = 39) were randomized in a 1:1 ratio to either low-dose (250 mg/day) sucroferric oxyhydroxide (SO) followed by high-dose (2000 mg/day) SO or vice versa, with washout phases before and after SO treatment. The primary endpoint was changed in calcification propensity as measured by calciprotein particle formation time (T50 test) between washout and high-dose SO treatment in patients with ≥85% adherence to the prescribed SO dose (per-protocol analysis). Results In the primary per-protocol analysis (n = 28), 2000 mg/day SO treatment resulted in a mean increase in T50 of 66 min (95% CI 49–84 min, P

Background Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. Methods This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). Results Eighty-five subjects (2–18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was − 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE − 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE − 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). Conclusions SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.

Background and objectives With multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade. Design, setting, participants, & measurements In a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006–2008, 2009–2011, and 2012–2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post–dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH. Results Among 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol–based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol–based strategies at dialysis initiation decreased across cohorts: 15% (2006–2008) to 5% (2012–2015). The proportion with active vitamin D sterol–based strategies after 18 months of dialysis decreased across cohorts: 52% (2006–2008) to 34% (2012–2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006–2008 and 2009–2011 cohorts, and increased to two- to three-fold in the 2012–2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement. Conclusions Over time, mineral metabolism management involved less use of vitamin D sterol–based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.

Although disturbed phosphate metabolism frequently accompanies chronic kidney disease (CKD), its causal role in CKD progression remains unclear. It is also not fully understood how excess salt induces organ damage. We here show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. In Dahl salt-sensitive rats, salt loading resulted in a significant increase in urinary phosphate excretion without altering serum phosphate levels. An intestinal phosphate binder sucroferric oxyhydroxide attenuated renal inflammation and proteinuria in this model, along with the suppression of phosphaturia. Using cultured proximal tubule cells, we confirmed direct pathogenic roles of phosphate-containing nanoparticles in renal tubules. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with altered phosphate metabolism. These data demonstrate that increased phosphate excretion promotes renal inflammation in salt-sensitive hypertension and suggest a role of disturbed phosphate metabolism in the pathophysiology of hypertensive kidney disease and high salt-induced kidney injury., Qin Wang et al. show that altered phosphate metabolism contributes to the progression of kidney disease using a salt-sensitive rat model. They demonstrate that using the phosphate binder sucroferric oxyhydroxide reduces kidney injury and, using transcriptome sequencing, identify a potential role for complement C1q in kidney inflammation linked to phosphate metabolism defects.

Background Administration of phosphate binders can decrease serum phosphate levels and improve the prognosis of patients on dialysis. However, patients are often non-adherent to phosphate binder medication. Although community pharmacist-led education could be effective in the maintenance of adherence to phosphate binder medication, its impact has not been evaluated. Objective We aimed to evaluate the impact of community pharmacist-led intensive education focusing on phosphate binders for patients receiving haemodialysis. Setting The study comprising three phases (baseline phase, intervention phase, and follow-up phase) was conducted at the Yamauchi Pharmacy, Japan. Method Six pharmacists provided intensive education focusing on phosphate binders to patients receiving haemodialysis. As intensive education, a sheet containing checks for the remaining phosphate binders and information advising the patients on the use of the drugs was issued. Using the check sheet filled in by the patient, the pharmacists repeatedly provided education appropriate to the individual patient's medication status and level of understanding to encourage the correct use of phosphate binders for 8 weeks (intervention phase). We investigated their serum phosphate levels from their medical records from 2 months before the start of intensive education (baseline phase) to 8 months after the end of the education (follow-up phase). Main outcome measure Serum phosphate levels in patients receiving haemodialysis after intensive education by community pharmacists. Results Fifty patients were enrolled in this study. During the intervention phase, serum phosphate levels in the patients with high and the highest serum phosphate level (6-7 mg/dL and ≥ 7 mg/dL, respectively) significantly decreased by 6.9% (P = 0.007) and 10.9% (P = 0.034), respectively. The levels remained below the baseline value throughout the follow-up phase in patients with the highest serum phosphate level. Conclusion Community pharmacist-led education focusing on phosphate binders affects short- and long-term management of serum phosphate levels in patients receiving haemodialysis, especially the patients whose levels were initially high.

Iron deficiency is a frequent comorbidity of cardiovascular (CV) diseases and nearly 50% of patients with heart failure (HF) with or without anaemia have low levels of available iron. There is a strong association between anaemia and the increase in mortality and hospitalizations in patients with CV disease and HF. Moreover, anaemia and chronic kidney disease (CKD) often coexist in patients with HF, with anaemia increasing the risk of death in these subjects and with a further increased risk in CKD population. The evidence that the treatment of iron deficiency and the increase in haemoglobin are associated with a better prognosis in HF patients has elicited new interest in the utilization of iron in HF and CKD patients. One of the central players in CV disease is vascular calcification (VC), which has been recognized as a major independent risk factor for incident CV disease and overall mortality in chronic disease patients. In this review, we summarize the evidences generated by clinical trials aimed to study the effect of iron deficiency correction, the effect of iron-based phosphate binder in in vivo models of kidney failure and the effect of iron in in vitro models of VC, trying to give an overview of the present knowledge on iron effect and its mechanisms of action.

Background With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear. Case presentation An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa. On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition. Conclusions Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Background Hyperphosphataemia is a common complication of chronic kidney disease (CKD). PT20 (ferric iron oxide adipate) is an investigational molecule engineered to offer enhanced phosphate-binding properties relative to other phosphate binders. Methods In this double-blind, parallel-group, placebo-controlled, dose-ranging study (ClinicalTrials.gov identifier NCT02151643), the efficacy and safety of 28 days of oral PT20 treatment were evaluated in patients with dialysis-dependent CKD. Participants were randomly assigned in an 8:8:8:13:13 ratio to receive PT20 (400, 800, 1600 or 3200 mg) or placebo three times daily. Results Among 153 participants, 129 completed treatment [7 discontinued because of adverse events (AEs), 2 because of hyperphosphataemia and 15 for other reasons]. PT20 treatment for 28 days resulted in a statistically significant and dose-dependent reduction in serum phosphate concentration. There were no statistically significant effects of PT20 treatment on changes in haemoglobin or ferritin concentrations or transferrin saturation between Days 1 and 29. The incidence of treatment-emergent AEs was broadly similar across the PT20 and placebo groups (42–59% versus 44%). The most common PT20 treatment-related AEs were gastrointestinal, primarily diarrhoea (13–18%) and discoloured faeces (3–23%). No serious AEs were considered to be related to study treatment. There were no clinically significant changes in laboratory results reflecting acid/base status or increases in ferritin that could indicate the absorption of components of PT20. Conclusions In this first study investigating the efficacy and safety of PT20 in patients with hyperphosphataemia and dialysis-dependent CKD, PT20 significantly lowered serum phosphate concentrations and was generally well tolerated., Graphical Abstract

AIMS Phosphate-lowering effects of ferric citrate were reported in several clinical trials, but mostly in small-scale studies. The aim of this meta-analysis was to investigate the efficacy and safety of ferric citrate in controlling hyperphosphataemia and iron-deficiency anaemia in chronic kidney disease (CKD) patients. METHODS PubMed, Embase and Cochrane Library were searched for clinical trials that enrolled CKD patients receiving ferric citrate for hyperphosphataemia. Two investigators performed systematic literature search to identify eligible studies, evaluated risk of bias and extracted relevant data. RESULTS Sixteen studies were included in the meta-analysis. Phosphate-lowering effects of ferric citrate were greater compared to no active treatment (standardized mean difference [SMD] = -1.15; P < 0.001) and comparable to other phosphate binders (SMD = 0.03; P = 0.61). Calcium concentrations post ferric citrate treatment did not differ compared to no active treatment (SMD = 0.15; P = 0.21) but were significantly lower compared to other phosphate binders (SMD = -0.14; P = 0.01). These led to significant reductions in calcium-phosphorus product with ferric citrate versus no active control (SMD = -1.02; P < 0.001) but no difference versus active control (SMD = -0.01; P = 0.93). Intact parathyroid hormone showed no substantial between-group difference in both comparison against no active and active controls. Ferric citrate improved iron stores and anaemia parameters, but increased risk of diarrhoea, abdominal pain and discoloured faeces. CONCLUSION Ferric citrate was effective in lowering phosphorus and phosphorus-calcium product versus no active treatment and had comparable effects versus other phosphate binders. Calcium levels were significantly lower with ferric citrate than with other phosphate-lowering treatment. Ferric citrate had additive effects on iron repletion and anaemia control and was associated with mostly gastrointestinal side effects.

Ferric citrate (FC), a novel oral phosphate binder, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving dialysis. FC binds to dietary phosphate in the gastrointestinal (GI) tract producing ferric phosphate that is excreted in feces. However, a small quantity of iron is systemically absorbed. There are limited data regarding the safety of the maximum approved dose of FC among peritoneal dialysis (PD) patients. We present a series of 3 PD patients who developed iron overload while receiving FC for management of hyperphosphatemia. These cases highlight the importance of close monitoring of iron studies and question whether a lower maximum dose of FC should be recommended in PD patients. Further studies are needed to assess the safety of the maximum approved dose of FC among PD patients.

Background The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models. Methods Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs. Results In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P Conclusions Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

Background Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown. Methods We performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D. Results Compared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI −0.9, −0.1) and 11.8 pg/ng (95% CI −20, −3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites. Conclusion Administration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

Rationale & Objective High pill burden associates with reduced phosphate-binder adherence among dialysis patients, contributing to elevated serum phosphorus levels. We compared the real-world effectiveness of sucroferric oxyhydroxide (SO) versus other phosphate binders in hemodialysis patients over 2 years. Study Design Retrospective cohort study. Setting & Participants Adult in-center hemodialysis patients prescribed 2 years of uninterrupted SO therapy (maintenance SO; n = 222) compared with patients who discontinued SO therapy (discontinued SO; n = 596) within 90 days of first prescription and switched to other phosphate binder(s) for 2 years. Exposures Phosphate binders. Outcomes Achievement of serum phosphorus levels ≤ 5.5 mg/dL, pill burden, and hospitalizations. Analytical Approach Comparisons were made quarterly (Q1-Q8) between maintenance SO and discontinued SO using Poisson and mixed-effects linear regression. Results Patients achieving serum phosphorus levels ≤ 5.5 mg/dL increased from baseline in maintenance SO (46 [20.7%] to a maximum of 104 [46.8%; P, Graphical Abstract

Ferric citrate is an oral iron-based phosphate binder, being known to affect iron status and improve iron deficiency anemia (IDA) in chronic kidney disease (CKD) patients. We examined whether oral administration of ferric citrate could change iron status and improve anemia without affecting phosphorus metabolism in iron deficiency anemia rats. In Normal rat study, normal rats were fed a diet containing 0.3 or 3% ferric citrate for 11 days for setting the dose and administration period of ferric citrate. The effects of ferric citrate on iron status- and phosphorus metabolism-related parameters were evaluated using blood and urine samples. Next, an iron deficiency anemia was induced by feeding iron-depleted diet in rats. After 7 days of starting the iron-depleted diet, 0.3% ferric citrate was administered for 7 days by dietary admixture. Iron status- and phosphorus metabolism-related parameters were evaluated with blood and urine samples. In Normal rat study, 3% ferric citrate treatment increased serum iron level and transferrin saturation (TSAT), and decreased serum phosphorus level, intact fibroblast growth factor 23 (iFGF23) level, and urinary phosphorus excretion, but 0.3% ferric citrate treatment showed no effects. On the other hand, in Iron deficiency anemia rat study, 0.3% ferric citrate treatment increased iron status-related parameters and improved anemia, but did not show any apparent changes in phosphorus metabolism-related parameters. In conclusion, ferric citrate could have hematopoietic effects without affecting phosphorus metabolism, and could be a potential option for the treatment of IDA in patients without CKD.

Background. Optimal phosphate control is an unmet need in chronic kidney disease (CKD). High serum phosphate increases calcification burden and is associated with mortality and cardiovascular disease in CKD. Nicotinamide (NA) alone or in combination with calcium-free phosphate binders might be a strategy to reduce phosphate levels and calcification and thus impact cardiovascular disease in CKD.Methods. We studied the effect of NA alone and in combination with magnesium carbonate (MgCO3) as a potential novel treatment strategy. CKD was induced in dilute brown non-agouti/2 mice by subtotal nephrectomy followed by a high-phosphate diet (HP) and 7 weeks of treatment with NA, MgCO3 or their combination. Control mice underwent subtotal nephrectomy and received an HP or underwent sham surgery and received standard chow plus NA.Results. CKD mice showed increased serum fibroblast growth factor 23 and calcium-phosphate product that was normalized by all treatment regimes. NA alone increased soft tissue and vascular calcification, whereas any treatment with MgCO3 significantly reduced calcification severity in CKD. While MgCO3 supplementation alone resulted in decreased calcification severity, it resulted in increased intestinal expression of the phosphate transporters type II sodium-dependent phosphate transporter 1 (Pit-1). Combined therapy of MgCO3 and NA reduced tissue calcification and normalized expression levels of intestinal phosphate transporter proteins.Conclusions. In conclusion, the data indicate that NA increases while MgCO3 reduces ectopic calcification severity. Augmented expression of intestinal phosphate transporters by MgCO3 treatment was abolished by the addition of NA. However, the clinical relevance of the latter remains to be explored. Importantly, the data suggest no benefit of NA regarding treatment of calcification in addition to MgCO3.

Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have not consistently proven to beneficially affect clinically relevant outcomes. The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) study is an international, multi-centre, randomized, placebo-controlled trial investigating the effect of the phosphate binder lanthanum carbonate on intermediate cardiovascular markers in patients with stage 3b–4 CKD. The primary end-point is change in carotid-femoral pulse wave velocity (PWV, SphygmoCor) after 96 weeks. Secondary outcomes include change in abdominal aortic calcification (AAC, computed tomography), serum phosphate and fibroblast growth factor 23 (FGF-23). In total, 278 participants were recruited and randomized, mean age 63 ± 13 years, 69% male, 45% diabetes, 32% CVD, 33% stage 3b CKD and 67% stage 4 CKD. Mean estimated glomerular filtration rate and serum phosphate were 26.6 ± 8.3 mL/min/1.72 m2 and 1.25 ± 0.20 mmol/L, respectively. Median (interquartile range) intact and c-terminal FGF-23 levels were 133.0 (89.1–202) pg/mL and 221.1 (154.3–334.1) RU/mL, respectively. Mean PWV was 10.8 ± 3.6 m/s and 81% had AAC (median Agatston score 1,535 [63–5,744] Hounsfield units). PWV ≥10 m/s was associated with older age, diabetes, CVD, presence of AAC, higher systolic blood pressure (BP), larger waist circumference and higher alkaline phosphatase. AAC was associated with older age, male sex, diabetes, CVD, higher diastolic BP, dyslipidaemia (and use of statins), smoking, larger waist circumference and increased PWV. In conclusion, IMPROVE-CKD participants had high baseline risk for cardiovascular events, as suggested by high baseline PWV and AAC values.

Background: Despite a growing population of patients starting hemodialysis in China, little is known about markers of mineral bone disease (MBD) and their management. We present data on prevalence and correlates of hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), with evaluation of whether these laboratory markers triggered changes in management. Methods: We compared the frequency of measurement and prevalence of poor control of MBD markers in China DOPPS with other DOPPS regions. We also used generalized estimating equations to assess correlates of MBD markers, and separate models to assess predictors of vitamin D and phosphate binder prescriptions in the China DOPPS. Results: Severe hyperphosphatemia (>7 mg/dL) and secondary hyperparathyroidism (>600 pg/mL) were common (27% and 21% prevalence, respectively); both were measured infrequently (14.9% and 3.2% of patients received monthly measurements in China). Frequency of dialysis sessions was positively associated with hyperphosphatemia; presence of residual kidney function was negatively associated with both hyperphosphatemia and secondary hyperparathyroidism. Laboratory measures indicating poor control of MBD were not associated with subsequent prescription of active vitamin D or phosphate binder. Conclusions: There are substantial opportunities for improvement and standardization of MBD management in China. Development of country-specific guidelines may yield realistic targets and standardization of medication use accounting for availability and cost. Key words: Mineral bone disease; Hyperphosphatemia; Hyperparathyroidism; China; Hemodialysis; Dialysis Outcomes and Practice Patterns Study

This cross-sectional study of 56 dialysis providers from 3 dialysis clinics examined providers’ attitudes and perception of autonomy support for patients’ medication adherence behaviors. Respondents completed surveys assessing attitudes and perception of autonomy support. Compared to all other provider types, physicians and nurse practitioners (MD/NP) thought it was “less true” that phosphate binder medications are very important for dialysis patients (MD/NP vs others: 5.1 [1.4] vs 6.1 [1.1]; P = 0.02). More dialysis technicians (19%) offered the highest level of support. Attitudes and perception of autonomy support for medication adherence are suboptimal, vary by dialysis provider type, and are targets for quality improvement in dialysis care. This study addresses critical gap in existing knowledge about these two novel provider-based psychosocial factors and their potential impact on phosphate binder medication adherence.

Phosphate binder pill (PBP) burden is a significant problem in dialysis patients. Phosphate absorption through the paracellular pathway increases in relatively acidic pH. In this study, we evaluated the effect of factors contributing to duodenal pH-Helicobacter pylori (HP), proton pump inhibitors (PPIs), and NaHCO3 capsules-on PBP burden. We evaluated 255 dialysis patients with gastric biopsies and excluded patients with low Kt/V, gastrectomy, and parathyroidectomy. Patients were divided into groups and subgroups regarding HP existence, use of PPI, or NaHCO3 capsules. HP+ group had significantly higher PBP burden and PBP equivalent doses (P < 0.001; both). HP+ subgroup not using daily PPIs or NaHCO3 capsules had the highest PBP burden and PBP equivalent doses (P < 0.001; both). HP- subgroups had similar PBP and PBP equivalent doses (P = 0.446 and P = 0.382; respectively). HP colonization might affect the PBP burden in dialysis patients due to a decrease of duodenal pH.

Background Elevated serum phosphorus concentrations are common among maintenance hemodialysis patients. Protein is a major source of dietary phosphate, but restriction of protein intake can result in hypoalbuminemia and protein-energy wasting. We hypothesized that sucroferric oxyhydroxide (SO), a potent phosphate binder with a low pill burden, may reduce serum phosphorus levels in hemodialysis patients with hypoalbuminemia without adversely impacting albumin levels or dietary intake of protein. Methods We retrospectively examined de-identified data from 79 adult, in-center hemodialysis patients with baseline hypoalbuminemia (≤ 3.5 g/dL) switched to SO as part of routine clinical care for at least 1 year. Temporal changes (3-month intervals from baseline through Q4) in phosphate binder pill burden, serum phosphorous levels, nutritional markers, and equilibrated Kt/V were analyzed. Data from a matched reference group of non-hypoalbuminemic patients (N = 79) switched to SO were also examined. Results SO therapy was associated with a mean reduction of 45.7 and 45.1% in daily phosphate binder pill burden, and a mean reduction of 0.4 mg/dL and 0.51 mg/dL in serum phosphorus levels for the hypoalbuminemic and non-hypoalbuminemic patients, respectively. Hypoalbuminemic patients demonstrated significant increases in mean serum albumin levels from 3.50 mg/dL at baseline to 3.69, 3.74, 3.70, and 3.69 mg/dL during Q1 through Q4, respectively (P Conclusions Both hypoalbuminemic and non-hypoalbuminemic patients switching to SO exhibited significant reductions in serum phosphorus concentrations and daily phosphate binder pill burden. Among hypoalbuminemic patients, the initiation of SO therapy was also associated with increases in serum albumin, suggesting therapy may have allowed patients to increase their dietary intake of protein.

Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. Annual inpatient cost-savings per patient in the mSO group versus the dSO group were ���1,201, ���2,097, ���2,059, ���1,512, and ���3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were ���327, ���1,585, ���1,022, ���1,100, and ���2,204, respectively. Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.

Background Fibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease. In this post hoc analysis of the ASTRIO study (UMIN000019176), we investigated the relationship between FGF23 and α-klotho during treatment with an iron-based phosphate binder, ferric citrate hydrate (FC), compared with non-iron-based phosphate binders in hemodialysis (HD) patients. We examined the effect of iron absorption by FC on the relationship between FGF23 and α-klotho. There have been few clinical studies evaluating these biomarkers simultaneously in HD patients. Methods The ASTRIO study was a 24-week, randomized, open-label, multicenter trial. HD patients taking non-iron-based phosphate binder(s) were randomized at a 1:1 ratio to continue other binder(s) (control group) or switch to FC (FC group). Serum phosphate (P) and hemoglobin (Hb) were maintained within 3.5–6.0 mg/dL and 10–12 g/dL, respectively. Plasma levels of intact FGF23 (i-FGF23), C-terminal FGF23 (c-FGF23), and α-klotho were measured, as were iron-related parameters. Association analyses of FGF23 and α-klotho were conducted. Results Patients were randomized to FC (n = 48) and control (n = 45) groups. Serum ferritin significantly increased from baseline to end-of-treatment (EOT) in the FC group, compared with the control group (adjusted mean difference [95% confidence interval]: 79.5 [44.7, 114.4] ng/mL; p e pg/mL vs. 0.2 ± 0.8 loge pg/mL, respectively; p = 0.04). The mean change from baseline to EOT in i-FGF23 and α-klotho were not significantly different between the FC and control groups (mean ± SD: − 0.1 ± 0.8 loge pg/mL vs. 0.1 ± 0.9 loge pg/mL; p = 0.33, and 2.0 ± 91.5 pg/mL vs. − 8.9 ± 145.3; p = 0.58, respectively). However, both forms of FGF23 and α-klotho were not significantly associated with each other in both groups. Conclusions Iron absorbed via FC administration in HD patients did not influence the correlation relationship between plasma levels of FGF23 and α-klotho under the condition of serum P and Hb were maintained. Trial registration ASTRIO study (UMIN000019176, registered at UMIN Clinical Trials Registry on October 1, 2015).

A 72‐year‐old female patient used the oral phosphate binder lanthanum carbonate for 6 years, before discontinuing it after receiving a pancreas and kidney transplant. Now, 7 years after discontinuation, the patient developed bilious emesis. An upper gastrointestinal endoscopy showed an unspecific gastritis. Biopsies showed subepithelial crystalline deposits consistent with gastric lanthanosis., After years of discontinuation of lanthanum carbonate, depositions can still be found in the gastric mucosa with associated gastrointestinal symptoms.

Objective: Sevelamer hydrochloride is a phosphate binder used to treat hyperphosphatemia in chronic kidney disease (CKD) patients that can reduce valvular and vascular calcification. The aim of this study was to examine the effects of sevelamer treatment on calcification in bioprosthetic heart valves (BHVs).Methods: Wister rats were randomly divided into three groups according to sevelamer intake and implantation (sham–sham operation; implant–implantation and normal diet, implant+S implantation, and sevelamer diet). Two kinds of BHVs—bovine pericardium treated with glutaraldehyde (GLUT) or non-GLUT techniques—were implanted in rat dorsal subcutis at 4 weeks. After implantation, sevelamer was administered to the implant+S group. The animals were executed at days 0 (immediately after implantation), 7, 14, 28, and 56. Calcium levels were determined by atomic absorption spectroscopy and von Kossa staining. Serum biochemistry analysis, Western blotting, real-time quantitative polymerase chain reaction, alkaline phosphatase activity measurement, histopathologic analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were conducted to identify the anti-calcification mechanism of sevelamer.Results: Non-GLUT crosslinking attenuates BHV calcification. Serum phosphate and calcium remained unreactive to sevelamer after a 14-day treatment. However, the mean calcium level in the implant+S group was significantly decreased after 56 days. In addition, the PTH level, inflammatory cell infiltration, system and local inflammation, and expression of Bmp2, Runx2, Alp, IL-1β, IL-6, and TNF-α were significantly reduced in the implant+S group.Conclusion: Sevelamer treatment significantly attenuated the calcification of BHVs and had anti-inflammation effects that were independent from serum calcium and phosphate regulation. Thus, sevelamer treatment might be helpful to improve the longevity of BHVs.

Treatment of chronic kidney disease (CKD) mineral bone disorder (MBD) is challenging in growing children due to the high amount of calcium needed for normal bone mineralization and the required dietary phosphate restriction, which often includes intake of calcium-rich products such as milk. Therefore, enteral calcium-intake (Ca-I) was calculated.Patients: We looked at pediatric CKD-Patients aged 0–6 years.Design: We used a retrospective analysis of Ca-I from dietary data collections. Ca-I below 60% or above 100% of the D-A-CH and the KDOQI reference values were considered as severe Ca deficiency or Ca overload, respectively.Results: We had 41 children, median age 1.1 (range 0-5.8) years, body weight 7.3 (2.4–19.9) kg, and length 68 (48-105) cm at the time of first dietary data collection. Renal function was classified as CKD stage III in 20, IV in 28, V in 44, and VD in 142 dietary data collections. At the first dietary data collection, 5 children were in the CKD stage III, 10 in IV, 9 in V, and 17 were on dialysis. Only one child progressed to a higher CKD stage. In total, 234 dietary data collections were analyzed, and 65 follow-up collections were available from 33 children after a time interval of 26 (1–372) days. The median caloric intake was 120 (47–217)% of D-A-CH RDI. In 149 (63.6%) of the dietary data collections, enteral Ca-I was below the target (p < 0.005 and r = −0.13, p < 0.05).Conclusion: Enteral Ca-I should repeatedly be monitored in CKD children because many may may otherwise be underexposed to enteral calcium and overexposed when calcium-containing phosphate binders are given. Our findings suggest a major impact of dietary calcium supply on bone health in pediatric CKD.

Sevelamer is a common phosphate binder used to manage hyperphosphatemia in end-stage renal disease. The medication has a well-documented gastrointestinal side-effect profile including nausea, vomiting and abdominal pain. There are few case reports of Sevelamer crystal deposition causing gastrointestinal mucosal injury, pseudotumor or obstruction. Here, we discuss a patient on Sevelamer who required operative management of a sigmoid obstruction. Surgical pathology showed pericolonic abscess with Sevelamer crystals.

We report a case of severe hypokalaemia and moderate hypophosphataemia from clay ingestion. A 60-year-old woman presented with flaccid paralysis. Investigations revealed a serum potassium level of 1.8 mmol/L, phosphate level of 0.56 mmol/L and creatine kinase level of 30 747 IU/L. She had marked proximal and distal muscle weakness due to severe hypokalaemia and concurrent hypophosphataemia, which likely contributed to the onset of rhabdomyolysis. The patient subsequently admitted to significant pica, most likely secondary to an associated iron deficiency. We conclude that the ingested clay acted as a potassium and phosphate binder. Although we did not investigate the content of the clay in this case, it has been reported that clay can bind potassium in vitro and is rich in minerals such as aluminium that could play a role in the binding of phosphate, although the exact mechanism remains unclear. The patient recovered fully and outpatient follow-up at 6 months and again at 40 months confirmed no electrolyte abnormality, myopathy nor any further geophagia.

High serum phosphate levels have been associated with increased morbidity and mortality in dialysis patients. Nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counselling, stronger phosphate removal by dialysis and prescription of phosphate binders. An individualized choice of phosphate binders is a desirable option to improve the poor adherence with these medications’ prescription that has been associated with hyperphosphataemia.

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Background and Aims Hyperphosphatemia is common in end-stage renal disease (ESRD) because of impaired renal phosphate excretion and is treated by dietary measures, dialysis techniques and the use of phosphate binder medication. It is one of the most important cardiovascular risk factors for dialysis patients. Our goal was to involve dialysis patients in the achievement of phosphate targets by self-adjusting the dose of Phosphate Binders (PB) on a meal-to-meal basis, according to the individual dietary P intake Method We conducted an interventional prospective single-arm study with a pre-post design. The inclusion criteria were patients with ESRD who had been receiving dialysis for more than three months, with dialysis schedule for four hours per session, three times per week, and who were older than 18 years of age. The primary endpoints of the study were the number of patients who reached the goal of serum phosphate before and after the training program and the weekly mean serum phosphate levels evaluated after the intervention period and compare them with the pre-intervention baseline levels. The secondary end-point was the burden of PB daily. All patients were trained in a self-administer PB program. A self-adjusted PB dose card was developed based on the phosphate food content list published by the National Technical University of Athens. The aim was to allow patients to immediately calculate the iP content of any food they consume easily. Phosphate Equivalent (PEQ) was defined as the weight of phosphorus having the same phosphate impact as a given weight of food. One PEQ corresponded in 100 mg of inorganic phosphorous and to one tablet of PB (one tablet of 800 mg of sevelamer). After 4 weeks (weeks 1-4) of washout from previous phosphate binders, eligible patients with serum phosphorus concentrations ≥ 6 mg/dl were included in the study. All patients received standard dietary phosphate counseling and a fixed dosing regimen of sevelamer PB was prescribed according to KDIGO and dialysis unit protocols for eight weeks (weeks 5-12 – pre-intervention period) In the 13th week, patients were asked to practice the self-administer PB program for eight more weeks. Results A total of 97 patients were screened for the study. 21 patients were excluded. 74 patients completed the study. The percentage of patients with uncontrolled phosphate levels reduced from 56.76% (42 out of 74) to 36.48 % (27 out of 74) in the post-intervention period. Of 9 patients who initially had a serum phosphorus level ≥9 mg/dl, 8 were reverted to phosphorus levels < 6 mg/dl at the end of the PEQ intervention period. There was a significant reduction of phosphate levels (prePEQ 7.42 ± 1.43 mg/dl vs. postPEQ 5.59 ± 1.82 mg/dL, p=0.036) and Ca × P levels (prePEQ: 67.1 ± 11.5 mg2/dL2; postPEQ: 51.9 ± 13.4 mg2/dL2, p=0.021) after patient education. There was a non-significant increase on serum calcium (pre PEQ: 8.13 ± 1.18 mg/dL; post PEQ: 8.56 ± 0.83mg/dL, p=0.515) and iPTH (prePEQ: 411 ± 376 pg/mL; postPEQ: 381 ± 321 pg/mL,p=0.13) Conclusion Our work shows that providing the patients with a relatively simple tool about the use of phosphate binders as PEQ is, we had a positive effect on the dialysis patients’ knowledge about the use of PB, phosphate content of their meals, and increase their sense of the necessity of the treatment and it was proved more effective than the standard fixed dose method. Using the PEQ education system was rewarding in an additional 20% of the patients with previous uncontrolled hyperphosphatemia. The PEQ education system is an efficient self-adjustment phosphate binder dosage tool in dialysis patients in reducing the serum phosphate level in our hemodialysis patients.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventu-ally, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 860329, FIS/Fondos FEDER (PI18/01366, PI20/00744, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM