Phosphate Binders Research Articles

High alumina refractory concretes bonded with calcium aluminate phosphate binder

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.

Gut Microbiota and Host Cometabolism Are Altered by Patiromer-Induced Changes in Serum and Stool Potassium

Gut Microbiota and Host Cometabolism Are Altered by Patiromer-Induced Changes in Serum and Stool Potassium

Uremic Vascular Calcification: The Pathogenic Roles and Gastrointestinal Decontamination of Uremic Toxins.

Uremic vascular calcification (VC) commonly occurs during advanced chronic kidney disease (CKD) and significantly increases cardiovascular morbidity and mortality. Uremic toxins are integral within VC pathogenesis, as they exhibit adverse vascular influences ranging from atherosclerosis, vascular inflammation, to VC. Experimental removal of these toxins, including small molecular (phosphate, trimethylamine-N-oxide), large molecular (fibroblast growth factor-23, cytokines), and protein-bound ones (indoxyl sulfate, p-cresyl sulfate), ameliorates VC. As most uremic toxins share a gut origin, interventions through gastrointestinal tract are expected to demonstrate particular efficacy. The “gastrointestinal decontamination” through the removal of toxin in situ or impediment of toxin absorption within the gastrointestinal tract is a practical and potential strategy to reduce uremic toxins. First and foremost, the modulation of gut microbiota through optimizing dietary composition, the use of prebiotics or probiotics, can be implemented. Other promising strategies such as reducing calcium load, minimizing intestinal phosphate absorption through the optimization of phosphate binders and the inhibition of gut luminal phosphate transporters, the administration of magnesium, and the use of oral toxin adsorbent for protein-bound uremic toxins may potentially counteract uremic VC. Novel agents such as tenapanor have been actively tested in clinical trials for their potential vascular benefits. Further advanced studies are still warranted to validate the beneficial effects of gastrointestinal decontamination in the retardation and treatment of uremic VC.

Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease.

Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.

Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial

IntroductionDespite widespread use of phosphate binders (PBs), phosphate control is insufficient in many hemodialysis patients. Preliminary clinical observations suggest that nicotinamide may act synergistically with PBs to improve phosphate control.MethodsThis multinational, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nicotinamide modified release (NAMR) in combination with oral PB in a large cohort of hemodialysis patients with abnormal serum phosphate concentration (>4.5 mg/dl) despite treatment with PB. Patients entered a proof-of-efficacy phase (12 weeks [W12]) in which adjustments of relevant comedication were not permitted, followed by a safety extension phase for up to 52 weeks. Here, we report the results of the first phase.ResultsThe intention-to-treat (ITT) population consisted of 539 patients in the NAMR and 183 patients in the placebo group. NAMR and placebo were orally administered once daily (250–1500 mg/d). Mean age of patients was 61.8 years, and 63.0% were men. In the confirmatory analysis that estimated the difference in serum phosphate concentration after 12 weeks, NAMR proved superior over placebo with a significant difference of –0.51 mg/dl (95% confidence interval [CI] –0.72, –0.29; P < 0.0001). This effect was associated with significantly lower intact parathyroid hormone (iPTH) values (NAMR: 292.4±300.4 pg/ml vs. placebo: 337.0±302.7 pg/ml; P = 0.04) and an improved calcification propensity (T50 time; NAMR: 23.8±97.1 minutes vs. placebo: 2.3±100.7 minutes; P = 0.02). Diarrhea and pruritus were more frequent in the NAMR group.ConclusionNAMR combined with oral PB significantly improved phosphate control in hemodialysis patients.

Association Between Implementation Of Novel Therapies And Improved Survival In Patients Starting Hemodialysis: The Swedish Renal Registry 2006-2015.

BackgroundThe recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients.MethodsThis was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks.ResultsAmong 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4).ConclusionsGradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.

A bundled phosphate control intervention (4Ds) for adults with end-stage kidney disease receiving haemodialysis: A cluster randomized controlled trial.

To evaluate the effectiveness of a bundled self-management intervention (taking control of your phosphate with the 4Ds) to improve phosphate control among adults receiving haemodialysis. Hyperphosphataemia occurs in end-stage kidney disease and is managed by diet, drinks, drugs (phosphate binder medication), and dialysis (the 4Ds). Adherence to the 4Ds is challenging for patients. A pragmatic cluster randomized controlled trial with repeated measures. Participants were adults receiving haemodialysis with high serum phosphate (>1.6mmol/L for at least 3months) recruited between August 2017 -May 2018. Cluster randomization was according to haemodialysis treatment shifts. The 'teach-back' intervention was designed to improve phosphate control. Expected outcomes were reduced serum phosphate and increased knowledge of phosphate in end-stage kidney disease, self-efficacy and adherence to diet, drugs, and dialysis. There were no differences between groups at baseline. Both groups had similar mean serum phosphate over time; at three months, 46% of the intervention group achieved reductions that met the target serum phosphate level compared with 33% of the control group. There were significant improvements in knowledge of phosphate in end-stage kidney disease, self-efficacy and adherence to diet, drugs, and dialysis (missing) in the intervention group compared with control group. The 4Ds, a bundled self-management intervention, was effective in improving patient confidence and adherence to phosphate control methods. The 4Ds intervention bundles together four essential strategies for preventing and controlling hyperphosphataemia in end-stage kidney disease. ACTRN12617000703303 Registered 16/05/2017.

Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis

Hyperphosphatemia is a risk factor for poor clinical outcomes in patients with kidney failure receiving maintenance dialysis. Opinion-based clinical practice guidelines recommend the use of phosphate binders and dietary phosphate restriction to lower serum phosphate levels toward the normal range in patients receiving maintenance dialysis, but the benefits of these approaches and the optimal serum phosphate target have not been tested in randomized trials. It is also unknown if aggressive treatment that achieves unnecessarily low serum phosphate levels worsens outcomes. Multicenter, pragmatic, cluster-randomized clinical trial. HiLo will randomize 80-120 dialysis facilities operated by DaVita Inc and the University of Utah to enroll 4,400 patients undergoing 3-times-weekly, in-center hemodialysis. Phosphate binder prescriptions and dietary recommendations to achieve the "Hi" serum phosphate target (≥6.5 mg/dL) or the "Lo" serum phosphate target (<5.5 mg/dL). Primary outcome: Hierarchical composite outcome of all-cause mortality and all-cause hospitalization. Main secondary outcomes: Individual components of the primary outcome. The trial is currently enrolling. HiLo will not adjudicate causes of hospitalizations or mortality and does not protocolize use of specific phosphate binder classes. HiLo aims to address an important clinical question while more generally advancing methods for pragmatic clinical trials in nephrology by introducing multiple innovative features including stakeholder engagement in the study design, liberal eligibility criteria, use of electronic informed consent, engagement of dietitians to implement the interventions in real-world practice, leveraging electronic health records to eliminate dedicated study visits, remote monitoring of serum phosphate separation between trial arms, and use of a novel hierarchical composite outcome. Registered at ClinicalTrials.gov with study number NCT04095039.

The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis

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.

An investigation on thermal behaviour of Sevelamer Carbonate and non-isothermal decarboxylation kinetics using TGA to obtain activation energy and pre-exponential factor

Sevelamer carbonate (SC) is a phosphate binder used to treat chronic kidney disease patients to remove excess phosphate. It is an insoluble drug and thus cannot be absorbed into the systemic circulation, so the in vivo bioequivalence studies cannot be performed. The USFDA, therefore, recommends in vitro phosphate binding tests and API-sameness tests to show the interchangeability of generic variants of the sevelamer carbonate tablets. The API-sameness mentions a variety of physicochemical characteristics including carbonate content. In this work, we studied the decarboxylation characteristics using thermal techniques (DSC & TGA). We have determined the activation energy and pre-exponential factor (Arrhenius parameters-Ea and A) that of the decarboxylation using nonisothermal kinetics of decarboxylation in combination with a well-accepted Coats-Redfern model-fitting method. A total of 13 different models were tested of solid-state reaction in which the second-order model suits best with an excellent correlation of 0.9926. The resultant values of the Ea and A are 25 kcal/mol and 1.23007 × 1012 Sec-1, respectively. The comparison of decarboxylation activation energy values may offer additional assurance on the API-sameness, in addition to comparing carbonate content alone.

Back Pain and Lower Extremity Sensory Loss in an ESKD Patient.

A 33-year-old man on maintenance hemodialysis for 6 years for ESKD secondary to IgA nephropathy presented with acute back pain and loss of sensation in his feet, in the absence of recent trauma. His past medical history included severe hyperparathyroidism, with intact parathyroid hormone levels (iPTH) more than ten times the upper limit of the normal range (80 pg/ml) for 4 years, despite the prescription of phosphate binders, calcitriol, cinacalcet, and—lately—etelcalcetide. Clinical examination was marked by symmetric sensory loss and weakness in the lower extremities, together with deep-tendon hyperreflexia and Babinski signs. Plasma levels of electrolytes were normal. iPTH (855 pg/ml) and alkaline phosphatase (500 IU/L; normal range, 40–130 IU/L) levels were unchanged. Magnetic resonance imaging …

Global Dialysis Perspective: South Africa.

South Africa is an upper middle–income country with a population of 59.6 million people (1). Gauteng is the most densely populated province, and houses 26% of the population, followed by KwaZulu-Natal (19%), and the Western Cape (12%). About 29% of the population are <15 years old and 9% are ≥60 years. Approximately 13% of the population are seropositive for HIV. Life expectancy is estimated at 68.5 years for females and 62.5 years for males, whereas the infant mortality rate is 23.6 per 1000 live births. In 2019, the gross national income per capita was approximately $6040 (Atlas method, current US$), with 8% of the country’s gross domestic product spent on health care (2). Despite the transition to democracy in 1994, a high level of inequality remains, reflected in a Gini coefficient of 0.63 and an unemployment rate of 30% (2,3). This inequality is also reflected in a two-tiered health system. Access to a well-resourced private health care sector depends on the ability to pay for services, usually via medical insurance. Treatment for CKD is included in the set of “prescribed minimum benefits” that all registered medical insurance schemes in South Africa are obliged to provide for their members. The majority of South Africans (84%), however, are dependent on an under-resourced, government-funded, public health care sector. Public health care facilities use a sliding scale, where the fees charged are dependent on income. Indigent patients are able to access services free of charge (4). South Africa is faced with a high burden of infectious diseases (such as tuberculosis and HIV infection), noncommunicable diseases, maternal and childhood diseases, and injury-related diseases (5). These factors drive an epidemic of AKI and CKD. Two studies have estimated the population prevalence of CKD in South Africa. Adeniyi et al. (6) reported the …

Effect of switching from cinacalcet to etelcalcetide on secondary hyperparathyroidism in patients undergoing hemodialysis: an ESCORT trial

BackgroundEtelcalcetide 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.MethodsOne 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.ResultsOf 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.ConclusionsThis study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet.Trial registrationUMIN, UMIN000027637; Registered on June 5, 2017.

Investigation of the clinical significance and pathological features of lanthanum deposition in the gastric mucosa

BackgroundThere are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population.MethodsWe compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images.ResultsThere was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180–3150 g] vs. 480 g [225–1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026).ConclusionsWe demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies.Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393).

Eficacia y seguridad de oxihidróxido sucroférrico en el tratamiento de la hiperfosforemia en la enfermedad renal crónica. Estudio FOSFASTUR

IntroductionAlterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SFO). ObjectiveTo analyse the efficacy and safety of SFO in 3 cohorts of patients, one with advanced CKD not on dialysis, another on peritoneal dialysis and the last on haemodialysis, followed for 6 months. MethodsA prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. ResultsEighty-five patients were included in the study (62±12 years, 64% male, 34% diabetic), 25 with advanced CKD not on dialysis, 25 on peritoneal dialysis and lastly, 35 on haemodialysis. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964±323mg/day. Overall, serum phosphate levels saw a significant reduction at 3 months of treatment (19.6%; P<.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, transferrin saturation index or haemoglobin, although there was a tendency for the last 2 to increase. Twelve patients (14%) withdrew from follow-up, 10 due to gastrointestinal adverse effects (primarily diarrhoea) and 2 were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1,147±371mg/day. ConclusionsSFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the 3 groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1,000mg/day. Diarrhoea was the most common side effect, although it generally was not significant.

Comparison of Sevelamer and Calcium Carbonate on Lipid Profile &amp; Hba1c in Diabetic Kidney Disease

Diabetic is a worldwide health issue and diabetic kidney disease is a dreaded complication of the disease. Drugs that can impair intestinal absorption of advanced glycation end products (AGE) can improve glycemic control and lipid profile. Sevelamer is a calcium free phosphate binder and has postulated to have a role in prevention of absorption of age. The aim of the study was to compare the mean change HbA1c and lipid profile in diabetic kidney disease by selvelamer vs calcium carbonate. The mean of the patient was 58.53 years. Sevelamer showed a mean decrease in HbA1c and lipid profile as compared to calcium carbonate (-0.57 + 45, -8.35 ± 9.006, -1.40 ± 7.07, -4.20 ± 4.26, vs -0.08 ± 0.21, 0.10 ± 2.51, 0.62 ± 1.03, 1.00 ± 1.55). However there was a mean rise in C-reactive protein. We concluded that sevelamer caused greater mean decrease that in HBA1c and lipid profile as compared to calcium carbonate but failed to decrease C- reactive protein.

Feasibility and Acceptability of mHealth Interventions for Managing Hyperphosphatemia in Patients Undergoing Hemodialysis

The objective of the study was to evaluate the feasibility and acceptability of mobile health (mHealth) phosphorus management programs in hemodialysis (HD) patients. Patients receiving thrice-weekly HD who had 3-month average serum phosphorus of >5.5mg/dL were randomized to one of the three self-directed phosphorus management programs delivered using tablet PCs: (1) educational videos and handouts (Education), (2) education intervention plus mobile self-monitoring with email feedback (Monitoring), or (3) education and monitoring interventions plus social cognitive theory-based behavioral videos (Combined). Feasibility and acceptability were assessed based on enrollment and retention and training needs (feasibility) and adherence to self-monitoring and reported satisfaction (acceptability). Of 312 patients, 56 expressed interest, and 40 were enrolled. The majority of participants (80%) completed the 6-month study; none withdrew for intervention-related reasons. The Monitoring and Combined groups received 44±15minutes of technology training, which was considered adequate by most (75%). Self-monitoring rates were initially high, with 78% and 71% of the participants recording at least one meal and phosphate binder in week 1, respectively, but decreased over time to 15% and 9% in the final week. Most participants reported that self-monitoring helped them stay motivated (64%), track nutrients (80%), and understand how to change diet (76%), and nearly two-thirds of participants (64%) stated that they would like to continue using the tablet PC to manage their health. However, few participants (16%) indicated that self-monitoring was worth the effort. The Monitoring and Combined groups did not differ from the Education group in study outcomes. Although the mHealth programs were generally well received, self-monitoring rates decreased substantially over time and were unaffected by social cognitive theory-based videos. Self-directed mHealth programs may be a useful adjunct to standard care but should be compared to more resource intensive programs (e.g., involving more "live" contact with a dietitian) to determine overall cost-effectiveness and role in HD care.

Effects of SNF472, a Novel Inhibitor of Hydroxyapatite Crystallization in Patients Receiving Hemodialysis — Subgroup Analyses of the CALIPSO Trial

IntroductionCoronary artery calcium (CAC) is highly prevalent and linked with poor outcomes in patients receiving maintenance hemodialysis, and its reduction may improve patient prognosis. SNF472, a selective inhibitor of hydroxyapatite crystallization, slows CAC progression in patients receiving maintenance hemodialysis. In this analysis, we assessed the efficacy of SNF472 in prespecified patient subgroups.MethodsIn a randomized clinical trial SNF472 300 mg, SNF472 600 mg, or placebo were infused thrice weekly in 91, 92, and 91 patients receiving maintenance hemodialysis and with CAC at baseline, respectively. In prespecified subanalyses, the percent change in CAC volume score (CACvs) from baseline to week 52 in modified intention-to-treat (mITT) and per-protocol (PP) populations was calculated in the following subgroups: age, sex, diabetes mellitus, dialysis vintage, prior atherosclerotic cardiovascular disease, baseline use of non-calcium and calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, and statins.ResultsIn the main trial, SNF472 significantly reduced CACvs progression compared with placebo (11% versus 20% mITT analyses; P = 0.016; 8% vs. 24% PP analyses; P < 0.001). Treatment differences for CACvs progression were similar across all subgroups, and all interaction P values were non-significant in mITT and PP analyses.ConclusionsSNF472 treatment for 52 weeks reduced CACvs progression compared with placebo in a broad range of patients receiving maintenance hemodialysis. Future studies will determine the impact of SNF472 on cardiovascular events in this population.

Adsorptivity of cationic cellulose nanocrystals for phosphate and its application in hyperphosphatemia therapy

Nanocellulose has gained much attention because of its excellent properties. Cationic cellulose nanocrystals (cCNC) shows good adsorptivity toward negative ions and molecules. Phosphate binders are most used to treat hyperphosphatemia and it is significant to develop its alternatives with high specific and low cost in the clinic. Herein, we prepared cCNC and characterized it by FTIR, TEM, dynamic light scattering, and viscosity method. We simulated the binding process of cationic cellulose for phosphate and used it as phosphate binder for hyperphosphatemia therapy to study the phosphate binding effect and evaluate the oral toxicity. Cationic cellulose improved the conditions of mice models and efficiently decreased the level of phosphate in the serum. cCNC had a better binding effect than cationic microcrystalline cellulose both in vitro and in vivo. cCNC could be used as alternatives to phosphate binder for therapy of chronic renal failure and hyperphosphatemia.

How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide

IntroductionThe lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it. MethodsProspective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed. ResultsThe percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users’ group (62.1–92.9%, p<0.001), but not in the control group (83–83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2–2.3 comp, p<0.001), but not in the control group (5.6–5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8–84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7–78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason. ConclusionsSFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.