Phosphate Binders Research Articles

#2028 Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: a systematic review and meta-analysis

Abstract Background and Aims Hyperphosphatemia is a common and clinically significant complication in severe chronic kidney disease (CKD), associated with higher cardiovascular adverse events and higher mortality rates. High serum phosphate is also associated with a heightened risk of cardiovascular issues such as hypertension, left ventricular hypertrophy, atherosclerosis, and vascular calcifications. Phosphate binders are commonly used in patients receiving renal replacement therapy (RRT), aiming to reduce and maintain serum phosphorus. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving RRT. Method Data sources included MEDLINE(PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with the search cut-off in October 2023. We examined RCTs that comparing sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving RRT. Data extraction followed the PICOS protocol and bias risk was assessed using the Rob-2 tool. We performed a meta-analysis combining the data from RCTs, using R-studio. The primary endpoint of this study is the change in the serum phosphorus levels from baseline to end of treatment. Secondary outcomes included changes in serum intact parathormone (i-PTH) levels from baseline to end of treatment as well as the adverse events ratio during the study period. Given the prevalence of gastrointestinal side effects for both drugs, which often leads to drug discontinuation or patient non-adherence, a separate analysis focused on gastrointestinal-related adverse events. Results Inclusion criteria were met by 5 RCTs. No statistically significant difference was found in serum phosphorus reduction between the two groups {MD: −0.07 mmol/l,95% CI-random effects: −0.15 to 0.02}. Similarly, serum i-PTH reduction showed no statistically significant difference between the two drugs {MD = −1.53 mg/dl, 95% CI = (−4.45, 1.4), p = 0.26, random effects model}. Adverse events were comparable between the groups (OR: 1.11, 95% CI: 0.65-1.88, random effects model). However, further analysis of gastrointestinal adverse evets indicated a 60% increase with sevelamer carbonate {OR: 1.60, 95% CI 1.31-1.97, common(fixed) effect model}. Funnel plot examination for both continuous and dichotomous outcomes revealed a high chance for small study effect and publication bias. Conclusion This meta-analysis found that sucroferric oxyhydroxide and sevelamer carbonate are equally effective in controlling serum phosphorus and i-PTH levels. Sucroferric oxyhydroxide, however, demonstrated a more favorable profile regarding gastrointestinal adverse events. Our findings suggest sucroferric oxyhydroxide as a valuable alternative for RRT patients who have difficulty tolerating sevelamer carbonate.

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value < 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

#2404 Predictors of mortality in patients with chronic kidney disease stages 3-4 without heart disease

Abstract Background and Aims Cardiovascular disease is common in patients with chronic kidney disease (CKD). This may, at least in part, explain the high risk of mortality in this patient group. The aim of the present study was to identify factors associated with mortality in patients with CKD stages 3 and 4 without a diagnosis of heart disease. Method Study subjects were derived from a cohort of patients with CKD stages 3 and 4 who were recruited from our Nephrology Outpatient Clinic between February 2009 and December 2011. Ninety-one patients without a diagnosis of heart disease were included in this cross-sectional study. Mortality data were collected in April 2023. Results All-cause mortality was 28.6% (26 patients) during a mean follow-up of 11.2 ± 2.7 years. Comparison of baseline data between non-survivors and survivors showed that non-survivors were significantly older, had lower glomerular filtration rate (GFR), higher ambulatory systolic blood pressure (ASBP), less nocturnal dipping of ASBP, higher carotid–femoral pulse wave velocity (cfPWV) and higher serum levels of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [Tables 1 and 2]. In addition, the proportion of patients with diabetes and on treatment with beta-blockers was elevated in non-survivors [Tables 1 and 2]. There were no statistically significant differences between groups in smoking history, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, alpha-blockers, statins, active vitamin D analogs, calcium-based or non-calcium-based phosphate binders. In a binary logistic regression analysis, to identify independent predictors of mortality, we included age, gender, baseline GFR, serum NT-proBNP, TnT, cfPWV, percent of nocturnal dipping of ASBP, diagnosis of diabetes, and treatment with beta-blockers. Only less nocturnal dipping of ASBP (Exp [β] value of 0.86, 95% CI 0.77–0.97, p = 0.016) and advancing age (Exp [β] value of 0.91, 95% CI 0.84–0.99, p = 0.024) significantly predicted all-cause mortality. Conclusion In patients with CKD stage 3 and 4 without a diagnosis of heart disease only older age and less nocturnal dipping of ASBP were independently associated with mortality. Although baseline levels of serum NT-proBNP and TnT were elevated in non-survivors, neither serum NT-proBNP nor TnT showed independent associations with mortality in this cohort.

#1579 The effectiveness and safety of sucroferric oxyhydroxide in the treatment of hyperphosphatemia in dialysis patients: a systematic review

Abstract Background and Aims Hyperphosphatemia is an independent prognostic factor for mortality in dialysis patients. The most widely used phosphate binders are sevelamer and lanthanum carbonate. Poor compliance may be due to high pill burden and gastrointestinal adverse reactions. Some previous studies on sucroferric oxyhydroxide showed a potential reduction of phosphorus levels and pill burden. This study aims to determine the effectiveness and safety profile of sucroferric oxyhydroxide in the control of hyperphosphatemia in dialysis-dependent patients. Method A systematic search was conducted in the Cochrane Library, MEDLINE, TRIP Database, and ClinicalTrials.gov until Jan 8, 2024. All randomized controlled trials on the use of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in adult dialysis patients were included. The comparator groups considered were sevelamer or lanthanum. The outcomes of interest were post-treatment serum phosphorus level, the change of serum phosphorus level from baseline, hemoglobin level, ferritin level, transferrin saturation level, adverse events, serious adverse events, and all-cause mortality. Two authors independently searched for articles, screened the articles for inclusion, and appraised the articles using the REVMAN risk of bias table. The GRADE was used to assess the certainty of evidence. In case of a disagreement, the two authors discussed until a consensus was reached. If a consensus was not reached, an independent third-party reviewer was consulted. Meta-analysis was conducted using Review Manager 5.4.1 software. Results We included 7 RCTs represented by 11 records and a total of 2031 adult dialysis patients with hyperphosphatemia. The usual dose of sucroferric oxyhydroxide is 750 mg-3000 mg/day. Sucroferric oxyhydroxide reduces serum phosphorus levels comparable to that of sevelamer (MD = −0.03 mmol/L, 95% CI −0.10 to 0.03, I2 49%) and of lanthanum (MD = −0.02 mmol/L, 95% CI −0.36 to 33, I2 0%). The decrease in serum phosphorus level from the baseline is also comparable with sevelamer (MD = −0.06 mmol/L, 95% CI −0.13 to 0.00, I2 59%). Sucroferric oxyhydroxide significantly reduces the daily number of tablet intake (MD = −7.09 tablets/day, 95% CI −10.45 to −3.73, p-value < 0.0001, I2 = 99%) compared to sevelamer. The use of sucroferric oxyhydroxide shows significantly higher hemoglobin level (MD = 1.15; 95% CI 0.92 to 1.39, p-value < 0.0001, I2 = 0%), higher transferrin saturation level (MD = 8.33; 95% CI 6.06 to 10.59, p-value < 0.0001, I2 = 0%) and higher ferritin level (MD = 64.16; 95% CI 31.64 to 96.68, p-value 0.0001) compared with the use of sevelamer. Pooled analysis on sucroferric oxyhydroxide showed no significant differences in adverse events (RR = 1.05, 95% CI 0.95 to 1.17, I2 = 47%); serious adverse events (RR = 1.11, 95% CI 0.84 to 1.47, I2 = 0%) and all-cause mortality (RR = 0.94; 95% CI 0.38 to 2.31, I2 = 0%) compared to sevelamer. The most common adverse events reported were nausea, diarrhea, abdominal discomfort, fecal discoloration, and hyperphosphatemia. Conclusion Sucroferric oxyhydroxide is comparable with sevelamer and lanthanum in decreasing serum phosphorus levels. It is also associated with higher hemoglobin, ferritin, and transferrin saturation levels compared with the sevelamer group. Since there are no significant differences in the risks of adverse events, serious adverse events, and all-cause mortality, the decrease in pill burden with sucroferric oxyhydroxide may help improve patient compliance.

#313 Enhanced urinary phosphorous reduction: comparative study of oxylanthanum carbonate and tenapanor in rat

Abstract Background and Aims End-stage renal disease (ESRD) affects >7 M people worldwide and ∼70% of patients with ESRD have hyperphosphatemia. Oxylanthanum carbonate (OLC) is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity vs other phosphate (P) binders, with a smaller pill size that is swallowed with water vs chewed. Tenapanor is a sodium hydrogen exchanger inhibitor used to reduce serum P in adults with chronic kidney disease (CKD) on dialysis. A previous study conducted by King et al found that when administered together, tenapanor and sevelamer decreased urinary p excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. Employing an identical study design and dosing regimen, the objective of our study was to evaluate the effects of tenapanor and OLC on P excretion. Method In our study, we utilized the study design and dosage regimen from King et al involving sevelamer and tenapanor. 64 male Sprague Dawley rats were fed standard chow 1 week prior to study start. On study day −1, animals were randomized into 3 study groups (n = 8): 1) vehicle, 2) tenapanor 0.15 mg/kg, 3) Vehicle + OLC 0.75%, 4) Vehicle + OLC 1.5%, 5) Vehicle + OLC 3%, 6) tenapanor 0.15 mg/kg + OLC 0.75%, 7) tenapanor 0.15 mg/kg + OLC 1.5%, and 8) tenapanor 0.15 mg/kg + OLC 3%. Vehicle and tenapanor were dosed PO twice/day whereas OLC was incorporated into the diets. 24-hour urine samples were collected using metabolic cages on day 9, 10, and 11 for urinary P measurements. Results Compared to vehicle alone (group 1), P reduction of tenapanor (group 2) was 8.5 mg/day (not significant), while P reduction of OLC (group 5) was 25.3 mg/day (significant). OLC had 16.8 mg/day more P reduction than tenapanor (Fig. 1). Conclusion OLC demonstrated 3x more effective urine P reduction vs tenapanor. Subsequent analyses will focus on examining the combination of tenapanor and OLC. Combining OLC and tenapanor utilizes 2 different mechanisms of action to manage P levels while having a low pill burden, which may lead to synergistic effects to be investigated in future studies.

#1018 Profiles of medication use in dialysis patients globally

Abstract Background and Aims Global patterns of medication use in dialysis have not been defined so far. This project aims to provide a real-world view of medication use in dialysis and to characterize therapeutic classes and types of medications. An anonymized dialysis dataset of a global kidney care network called Apollo Dial DB was used. The most common prescribed medications administered at home by the patients were assessed. Method This is a multi-center, retrospective study using real-life data from adult dialysis patients captured in the first version of the Apollo Dial DB dataset. This dataset contains anonymized dialysis data (longitudinal observation level data) on more than 540,000 unique dialysis patients in 40 countries from Jan 2018-Mar 2021. Home medications were analyzed based on Anatomical Therapeutic Chemical (ATC) codes. Top (most common) 5 ATC codes for home medication are presented, once as 4-digit ATC code classes (e.g., A12A for Calcium) and once as full/exact ATC code (e.g., A12AA04 as 7-digit code for Calcium carbonate). Results In Apollo Dial DB 497,723 patients had 10,538,324 documented home medication entries (on average 21 medication prescriptions per patient outside the dialysis clinic), thereof 114,978 patients had 1,607,168 ATC code entries. Each ATC code entry represents a documented prescription of individual length. All percentages shown below are related to 1,607,168 ATC code entries (not to patients). The top 4-digit ATC code classes of home medication were Calcium (8.60%), Vitamin A and D, including combinations (7.33%), All other Therapeutic Products (6.84%), Antithrombotic Agents (5.89%) and Selective Calcium Channel Blockers with mainly vascular Effects (5.39%) (Fig. 1). Out of the ATC class Calcium, Calcium carbonate (4.89%) and Calcium acetate (3.22%) are listed as number 1 and 3 of the top 5 ‘full’ ATC codes. Alfacalcidol (3.36%) of ‘Vitamin A and D, including combinations’ is also number 2 of the ‘full’ ATC code list. Amlodipine (3.07%), number 4 of the full ATC code list, represents the majority of ‘Selective Calcium Channel Blockers with mainly vascular Effects’. Sevelamer of ‘All other Therapeutic Products’ is listed as number 5 in the ATC code list with 2.91% (Fig. 2). Conclusion The top 5 home ATC classes of medications account for 34% of all home prescriptions in dialysis patients. They largely represent phosphate binders, vitamin A & D, antithrombotics, and antihypertensives/antiarrhythmic medications. Although, outside the dialysis clinic each patient has on average 21 medication prescriptions, a lot of these prescriptions represent the major medication classes. It is worthwhile to mention the presented data are related to prescriptions and not to duration of use, e.g., both a medication prescribed for 6 months and a prescription for 1 week are documented only once, even if time on drug varies. Further research is needed to explore global patterns, including further ATC code groups particularly on a patient level, accounting for duration of use and medication formulations, real-world application of various drugs (e.g., GLP1 drugs, HIF PH inhibitor) and accounting for US data with NDC codes.

#586 Effects of nursing facility residency on mortality in incident HD patients

Abstract Background and Aims As the elderly population increases and nuclear families are formed, the number of elderly people who are managed in nursing facility is increasing. We investigated whether dialysis performed while residing in a nursing facility before dialysis affects the mortality rate of dialysis patients. Method We enrolled 2,597 patients who visited the hemodialysis clinics of 17 teaching hospitals and surveyed the characteristics of underlying diseases, laboratory findings, and medication between patients who started dialysis while admitted to a nursing facility and those who did not. Then, multivariate survival analysis was performed to see if starting dialysis after entering a nursing facility increased mortality. Results 9.1% (n=237) of the subjects underwent dialysis while admitted to a nursing facility. This group was predominantly female and older. Also the prevalence of diabetes, dementia, heart failure and atrial fibrillation was higher. There were many users of anti-platelet agents, warfarin, dementia drugs, and antidepressants. Additionally this group showed lower weight, lymphocyte, iPTH, albumin, phosphorus, and total cholesterol and higher duration of diabetes, and alkaline phosphatase. In multivariate analysis controlling for age, sex, access type, dementia, malignancy, ischemic heart disease, cerebrovascular accident, heart failure, atrial fibrillation, liver cirrhosis, fracture, coronary artery disease, ejection fraction, lymphocyte, platelet, BUN, Cr, albumin, phosphorus, total cholesterol, RAS blockade, B-blocker, calcium channel blocker, warfarin, hyperlipidemia drugs, Calcium-based phosphate binder, sevelamer, anti-depressant, and dementia medication, the HR of group receiving dialysis after being admitted to a nursing facility was 1.658 [1.309, 2.100]. Conclusion In summary, the current study suggests a correlation between starting dialysis in a nursing facility and a higher mortality rate among dialysis patients.

#1585 Ten years’ practice with calcimimetics and paricalcitol for the treatment of secondary hyperparathyroidism. Experience of one dialysis center

Abstract Background and Aims Secondary hyperparathyroidism (SHPT) remains one of the main problems in patients with chronic kidney disease (CKD), associated with deterioration in quality of life, progression of cardiovascular complications and mortality. Method Patients on HD (n = 2517) were treated from 2012 to 2023 years in our dialysis center with secondary SHPT were included in this study. All patients were divided into 2 groups: 1 gr. included −1536 (61%) patients whose PTH levels remained in the target range from 300 to 600 pg/ml, without therapy or with low doses of alfacalcidol (0.75-5 μg/week ); 2 gr. included - 981 (39%) patients with PTH levels >600 pg/ml were treated with calcimimetics (doses of cinacalcet used from 30 mg to 90 mg/day, doses of etelcalcetide used from 5 to 15 mg/week) as monotherapy or in combination with paricalcitol (5–15 μg/week). Phosphorus levels were controlled by an adequate dose of dialysis and administration of phosphate binders (sevelamer and sucrose iron oxyhydroxide). Results The average PTH level in 2 gr. of patients at the time of treatment initiation was 916.7 ± 879.9 pg/ml (601-2500 pg/ml). During the treatment the level of PTH decreased to target values and amounted 523.4 ± 216.7 pg/ml (63-594 pg/ml) in 73% of patients. Monotherapy with calcimimetics was effective in 41%; the remaining of patients (59%) were required the addition of paricalcitol to therapy to achieve target PTH values. Therapy of SHPT was also carried out in 15 (0.6%) patients with identified parathyroid adenomas (volume more than 1 cm3) and PTH levels >1000 pg/ml; the effect was achieved in 9 patients (60%), 6 patients underwent parathyroidectomy. During the previous years of observation, parathyroidectomy was required in all patients with SHPT with similar changes in the parathyroid glands. Conclusion In the overwhelming majority of patients with CKD5D and SHPT, the administration of calcimimetics as monotherapy or in combination with paricalcitol during the progression of SHPT allowed us to achieve target PTH values and maintain it for a long time (from 1 to 10 years), as well as reduce the number of surgical interventions for parathyroid glands, compared to the previous period.

#2296 Time to get calciphylaxis on clinicians’ RaDaR?—a multicentre case series

Abstract Background and Aims Calciphylaxis is a rare, severe complication of chronic kidney disease mineral bone disorder. It is hosphorzed by arteriolar calcification of the subcutaneous fat and dermis, and associated with a mortality rate of approximately 50% within a year of diagnosis. The reported prevalence of calciphylaxis in dialysis patients ranges from 1–4%. Between March 2012 and March 2020 the UK calciphylaxis study (UKCS) recruited 139 patients from 36 enrolled renal centres; an average of 1 case every 2.6 years per centre. The multicentre case series presented here includes patients from two NHS Hospital Trusts in the UK. The aim is to raise awareness of i) calciphylaxis and possible risk factors and ii) the role of registry data in rare kidney diseases. Method Patients were included if they had a diagnosis of calciphylaxis between 01.02.2020 and 01.02.2022. Data regarding demographics, dialysis modality, BMI, medications, and mineral bone parameters were collected from clinical databases. A representative sample of results was recorded from initiation of renal replacement therapy through to diagnosis of calciphylaxis. Data regarding calciphylaxis lesions, treatments and current vital status are hosphorz. Results 17 patients with end stage kidney failure (ESKF) and clinical features of calciphylaxis were included; 8 of 17 (47%) had a skin biopsy of which 6 reported evidence of calcification. Median age was 57 years (IQR: 50-74), BMI 26.8 kg/m2 (IQR: 22.9-31.1), 100% were white, 53% female and 59% had diabetes. Median time from onset of ESKF to calciphylaxis diagnosis was 5.5 years (IQR: 1-16). 53% (9 of 17) had history of recurrent hypercalcaemia (corrected calcium >2.55 mmol/L) and 82% (14 of 17) recurrent hyperphosphatemia (phosphate >1.5 mmol/L). 41% (7 of 17) had refractory secondary hyperparathyroidism. Warfarin therapy exposure was recorded in 47% (8 of 17) patients; a finding consistent with the literature. 76% (13 of 17) had received active vitamin D and 76% (13 of 17) a calcium-based phosphate binder. 76% (13 of 17) had lower leg lesions; 2 of whom also had upper leg lesions. 1 patient had a thigh lesion and 2 patients had an abdominal wound. Median follow up time was 8.5 months (range 1-24). 9 of the 17 patients remain alive, of whom lesions have completely healed in 6 patients. All patients received sodium thiosulphate and 1 (transplant patient) received hyperbaric oxygen therapy and sodium thiosulphate. Only 1 patient has been enrolled into the UK registry of rare kidney diseases (RaDaR). Conclusion Calciphylaxis is a devastating condition for which there are no proven treatments. In this case series a history of hyperphosphataemia, calcium-based binder, alfacalcidol, and warfarin use were common. It remains unknown why some patients develop calciphylaxis and others do not. National registry data, such as RaDaR, plays a crucial role in furthering knowledge and understanding of rare diseases; it helps to determine calciphylaxis incidence, and inform possible prevention and treatment strategies. Yet, in reality, few patients maybe being recruited into RaDaR. The opportunity exists for an international calciphylaxis registry; for this to offer maximum impact individual countries need to explore, and where possible address, barriers to recruitment.

Rapid, Direct Fabrication of Thermochromic Ceramic Composite Sensors via Flash Lamp Annealing

An inorganic, high‐temperature (≈600 °C) thermochromic sensor is synthesized from a chemically bonded ceramic composite. The ceramic composite is composed of thermochromic 10 wt% chromium‐doped alumina (Cr:Al2O3) powder blended with a low‐reacting temperature (around 250 °C) phosphate binder, Al(H2PO4)3, (aluminum dihydrogen phosphate [ADP]). Cr‐doped alumina exhibits thermochromism at high temperatures, typically around 500–600 °C. Previously, infrared (IR) irradiation has been used to successfully convert ADP to an aluminum phosphate (AlPO4) ceramic phase that can bind ceramic components together. Here, an ultrahigh‐power (tens of kilowatts per square centimeter) flash lamp annealing (FLA) system is evaluated as an alternative photonic heating process to rapidly transform ADP to this ceramic. While IR lamps require 30 min to fully transform the ADP binder, FLA processes require less than 1 min and provide more dense microstructures, opening opportunities to additively manufacture ceramic components without the need for a post‐processing heating step. Final ceramics exhibit reversible thermochromic behavior, transitioning from pink to dark gray as the temperature increases from 25 to 600 °C. Here, the ability to use this technology to fabricate a temperature warning system for heated objects that are not yet emitting significant visible black‐body radiation is demonstrated.

Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease.

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. The femoral neck's BMD decreased from 0.836g/cm2 (0.702-0.952) to 0.764g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833g/cm2 (0.736-0.965) to 0.824g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [β-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [β-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CBPB administration may be associated with BMD maintenance.

Comparison between calcium and non-calcium-based phosphate binders concerning acid-base status and electrolytes in Hemodialysis patients in ALHYAT hospital.

Comparison between calcium and non-calcium-based phosphate binders concerning acid-base status and electrolytes in Hemodialysis patients in ALHYAT hospital.

239 Tenapanor Treatment Added to Phosphate Binders Improved Long-Term Serum Phosphate (P) Control as Measured by Reduction in Average Daily P Area Under the Curve

239 Tenapanor Treatment Added to Phosphate Binders Improved Long-Term Serum Phosphate (P) Control as Measured by Reduction in Average Daily P Area Under the Curve

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

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

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

ObjectiveHyperphosphatemia is a common complication in patients with kidney failure, despite the use of phosphate binders (PBs). Vitamin B3, either in the form of niacin or niacinamide (NAM), shows potential as “add-on” treatment to reduce serum phosphate concentrations in this population. NAM seems to lack many of the side-effects that are observed with niacin. The aim of this study was to investigate whether NAM is an effective and acceptable treatment in reducing serum phosphate concentrations in patients with kidney failure. MethodsDiaNia was a double-blind placebo-controlled randomised crossover trial, comparing NAM (250-500 mg/day) to placebo as “add-on” treatment to an individual treatment with approved PBs for 12 weeks in patients receiving hemodialysis. The primary outcome was serum phosphate concentrations, and the secondary outcomes were platelet counts as well as drop-outs due to side-effects. Data was analysed using both per-protocol (PP) and intention-to-treat (ITT) analyses. ResultsMean age of the PP population (n=26) was 63.6 ± 17.2 years and 53.8% were men. NAM treatment significantly reduced serum phosphate with 0.59 mg/dL (p=0.03). Linear mixed models (LMMs) demonstrated superiority of 12 weeks NAM over 12 weeks placebo with a between-treatment difference of 0.77 mg/dL (95% CI 0.010, 1.43; p=0.03). Similar results, although not significant, were found in the ITT population. We found no between-treatment differences in platelet counts and during the NAM treatment we observed three drop-outs due to side effects (8.6%). ConclusionNAM is effective in reducing serum phosphate concentrations in patients with kidney failure receiving hemodialysis. In addition, NAM is well-tolerated and seems not to increase the risk of thrombocytopenia. Thus, NAM can be valuable as “add-on” treatment to combat hyperphosphatemia in patients with kidney failure. However, more research in larger populations is needed to confirm this.

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

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

Tenapanor (Xphozah) for hyperphosphatemia in chronic kidney disease.

The FDA has approved the sodium/hydrogen exchanger 3 (NHE3) inhibitor tenapanor (Xphozah – Ardelyx) to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy when phosphate binders are ineffective or as monotherapy when phosphate binders cannot be tolerated. Tenapanor is the first NHE3 inhibitor to be approved in the US for hyperphosphatemia. It was previously approved as Ibsrela to treat irritable bowel syndrome with constipation (IBS-C).

Identifying individuals at risk of needing CKD associated medications in a European kidney disease cohort

BackgroundThe consequences of chronic kidney disease (CKD) can be addressed with a range of pharmacotherapies primarily prescribed by nephrologists. More accurate information regarding future CKD-related pharmacotherapy requirements could guide clinical decisions including follow-up frequency.MethodsFollowing assignment to derivation and validation groups (2,1), variables predicting individually future use of vitamin D receptor agonists (VDRA), phosphate binders, erythropoiesis stimulating agents (ESAs) and iron were identified using logistic regression in a prospective cohort study containing demography, comorbidity, hospitalization, laboratory, and mortality data in patients with CKD stage G4/G5 across six European countries. Discriminative ability was measured using C-statistics, and predicted probability of medication use used to inform follow-up frequency.ResultsA total of 2196 patients were included in the analysis. During a median follow-up of 735 days 648 initiated hemodialysis and 1548 did not. Combinations of age, diabetes status and iPTH, calcium, hemoglobin and serum albumin levels predicted the use of ESA, iron, phosphate binder or VDRA, with C-statistics of 0.70, 0.64, 0.73 and 0.63 in derivation cohorts respectively. Model performance in validation cohorts were similar. Sixteen percent of patients were predicted to have a likelihood of receiving any of these medications of less than 20%.ConclusionsIn a multi-country CKD cohort, prediction of ESA and phosphate binder use over a two-year period can be made based on patient characteristics with the potential to reduce frequency of follow-up in individuals with low risk for requiring these medications.

Vascular Calcification: A Passive Process That Requires Active Inhibition.

The primary cause of worldwide mortality and morbidity stems from complications in the cardiovascular system resulting from accelerated atherosclerosis and arterial stiffening. Frequently, both pathologies are associated with the pathological calcification of cardiovascular structures, present in areas such as cardiac valves or blood vessels (vascular calcification). The accumulation of hydroxyapatite, the predominant form of calcium phosphate crystals, is a distinctive feature of vascular calcification. This phenomenon is commonly observed as a result of aging and is also linked to various diseases such as diabetes, chronic kidney disease, and several genetic disorders. A substantial body of evidence indicates that vascular calcification involves two primary processes: a passive process and an active process. The physicochemical process of hydroxyapatite formation and deposition (a passive process) is influenced significantly by hyperphosphatemia. However, the active synthesis of calcification inhibitors, including proteins and low-molecular-weight inhibitors such as pyrophosphate, is crucial. Excessive calcification occurs when there is a loss of function in enzymes and transporters responsible for extracellular pyrophosphate metabolism. Current in vivo treatments to prevent calcification involve addressing hyperphosphatemia with phosphate binders and implementing strategies to enhance the availability of pyrophosphate.