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Valeria Cernaro, Elisa Longhitano, Chiara Casuscelli, Luigi Peritore, Domenico Santoro Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina, ItalyCorrespondence: Domenico Santoro, Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, Messina, 98124, Italy, Email domenico.santoro@unime.itAbstract: Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.Keywords: Chronic Kidney Disease-Mineral Bone Disorder, CKD-MBD, diet, phosphate binders, phosphate intestinal absorption, tenapanor

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. [ABSTRACT FROM AUTHOR]

Abstract Background The 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. Methods Following 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. Results A 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%. Conclusions In 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.

Background: The 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. Methods: Following 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. Results: A 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%. Conclusions: In 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. [ABSTRACT FROM AUTHOR]

The critical importance of phosphate regulation in chronic kidney disease (CKD) has been well understood for decades. But new findings, frequently applicable to routine medical care, continue to evolve. Poor health outcomes, greater morbidity, lowered quality of life, and a higher death rate from cardiovascular disease are all linked to the development of CKD-bone mineral ailment. Increased blood phosphate levels are linked to an increased risk of mortality in hemodialysis patients due to changes in phosphate breakdown and declining renal function as CKD advances.In this setting, according to CKD-mineral bone disease recommendations, it is critical to regulate serum phosphate levels in patients with CKD-mineral bone problem. If dialysis and dietary intervention fail to control blood phosphate levels, the use of phosphate binders is advised. Although phosphate binders are successful in lowering blood phosphate levels by actively binding to dietary phosphate, certain individuals have adverse effects that may restrict their use.These medications also have a significant pill load, which might result in poor treatment compliance. Tenapanor, a novel medication, works by inhibiting the sodium/hydrogen exporter isoform 3 (NHE3), which lowers intestinal phosphate absorption primarily by decreasing passive paracellular phosphate flow. Tenapanor also reduces the expression of the sodium phosphorus 2b transport protein (NaPi2b), which limits active transcellular phosphate absorption compensation. This is considered to be more effective phosphorous absorption regulator and a better target for tailored medication therapy. This clinical study aggregate report explores the currently published studies that have evaluated Tenapanor for the treatment of hyperphosphatemia in end stage renal disease patients on haemodialysis. [ABSTRACT FROM AUTHOR]

In patients treated with peritoneal dialysis (PD), lowering the calcium level in PD fluids results in lower serum calcium levels and higher parathyroid hormone (PTH) levels. It is hypothesized that this effect is attenuated when patients are using icodextrin 7.5% for the once-daily long dwell (containing high calcium concentration). In this case series, we included 8 stable PD patients (mean age 68 ± 13 years, 7 male), all using icodextrin 7.5% (containing 1.75 mmol/L calcium) for the once-daily long dwell. The calcium content of the PD fluids for the remaining dwells was lowered from 1.75 mmol/L to 1.25 mmol/L. Bone mineral parameters and phosphate prescription at baseline, 6 weeks after this change, and after 6 months were compared. After lowering calcium concentration of the PD fluids – except for the icodextrin 7.5% – from 1.75 mmol/L to 1.25 mmol/L, calcium levels changed from 2.32 ± 0.11 to 2.29 ± 0.12 (p = NS); intact PTH (iPTH) from 39.6 ± 28.3 to 64.9 ± 34.5 pmol/L (p = 0.045); and alkaline phosphatase from 104.13 ± 48.75 to 101.38 ± 32.39 (p = NS). After 6 months, all bone mineral parameters were similar to baseline levels; however, slightly higher calcium-based phosphate binders were prescribed. Lowering calcium content from 1.75 mmol/L to 1.25 mmol/L in PD fluids in patients on icodextrin resulted in stable calcium values, a temporal increase in iPTH and a modest increase in calcium-based phosphate binder prescription. Using icodextrin for the long once-daily dwell appears to attenuate the effects on bone mineral parameters when lowering the calcium concentration of the short dwells.

Patients with kidney failure and early stages of chronic kidney disease often develop hyperphosphatemia, which is associated with negative outcomes. The reduction of phosphate levels is the established clinical practice. However, achieving and maintaining target phosphate levels is challenging, and the current methods of phosphate management lead to poor quality of life (QoL) in patients receiving dialysis, particularly because patients might not receive adequate education on phosphate control. Patients receiving dialysis are advised to maintain stringent dietary restrictions and might experience anxiety and depression due to the constant burden of dietary self-management. The lack of nutritional information on food labels makes adhering to dietary restrictions even more confusing and difficult. Phosphate binders are the only pharmacologic treatment currently indicated for hyperphosphatemia. However, phosphate binders have a limited binding capacity and are difficult to incorporate into patients' daily routines. Because of the suboptimal efficacy of phosphate binders and the negative impact of dietary restrictions on patient QoL, novel therapies for more effective phosphate control are needed. New treatment options that control phosphate levels would enable patients to eat a more normal, healthy diet and potentially improve their QoL.

Fibroblast growth factor 23 (FGF-23) has been associated with increased cardiovascular risk and poor survival in dialysis patients. It is well established that FGF-23 synthesis is directly induced by positive phosphate (P) balance. On the other hand, P-lowering treatments such as nutritional P restriction, P binders and dialysis are capable of reducing FGF-23 levels. However, there are many uncertainties regarding the possibility of adopting FGF-23 to guide the clinical decision-making process in the context of chronic kidney disease–mineral bone disorder (CKD-MBD). Furthermore, the best assay to adopt for measurement of FGF-23 levels (namely the intact vs the C-terminal one) remains to be determined, especially in conditions capable of altering the synthesis as well as the cleavage of the intact and biologically active molecule, as occurs in the presence of CKD and its complications. This Editorial discusses the main insights provided by the post hoc analysis of the NOPHOS trial, with particular attention given to evidence-based peculiarities of the intact and the C-terminal assays available for measuring FGF-23 levels, especially in patients receiving additive P-lowering therapy in the presence of inflammation, anemia and iron deficiency. [ABSTRACT FROM AUTHOR]

Abstract Background Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging‐related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. Methods Five‐month‐old (young), 24‐month‐old (old) and 28‐month‐old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low‐phosphate (low‐P) diet (0.2% phosphate) for 3 or 7 months, respectively. A phosphate binder, Velphoro®, was also supplemented in a group of old mice, mixed with a standard milled diet for 3 months. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. Results Old mice fed with low‐P diet showed reduced serum phosphate concentration (16.46 ± 0.77 mg/dL young; 21.24 ± 0.95 mg/dL old; 17.46 ± 0.82 mg/dL low‐P diet). Old mice fed with low‐P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice (P = 0.004). NMRI revealed a significant reduction in T2 relaxation time (P = 0.014) and increased magnetization transfer (P = 0.045) and mean diffusivity (P = 0.045) in low‐P diet‐treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice (P = 0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet (P = 0.004 and P = 0.014, respectively). Physical performance was also improved, increasing gait speed by 30% (P = 0.032) and reducing transition time in the static rod by 55% (P = 0.012). Similar results were found when diet was supplemented with Velphoro®. Conclusions The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro®, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.

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

BackgroundPhosphate 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.MethodsWe 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.ResultsCompared 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.ConclusionAdministration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

Background Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. Methods The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. Results A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6–49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4–5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval −39.2, 36.4), P = 0.65] or CPP-II [−18.3% (95% confidence interval −40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. Conclusions Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort. [ABSTRACT FROM AUTHOR]

In patients treated with peritoneal dialysis (PD), lowering the calcium level in PD fluids results in lower serum calcium levels and higher parathyroid hormone (PTH) levels. It is hypothesized that this effect is attenuated when patients are using icodextrin 7.5% for the once-daily long dwell (containing high calcium concentration). In this case series, we included 8 stable PD patients (mean age 68 ± 13 years, 7 male), all using icodextrin 7.5% (containing 1.75 mmol/L calcium) for the once-daily long dwell. The calcium content of the PD fluids for the remaining dwells was lowered from 1.75 mmol/L to 1.25 mmol/L. Bone mineral parameters and phosphate prescription at baseline, 6 weeks after this change, and after 6 months were compared. After lowering calcium concentration of the PD fluids – except for the icodextrin 7.5% – from 1.75 mmol/L to 1.25 mmol/L, calcium levels changed from 2.32 ± 0.11 to 2.29 ± 0.12 (p = NS); intact PTH (iPTH) from 39.6 ± 28.3 to 64.9 ± 34.5 pmol/L (p = 0.045); and alkaline phosphatase from 104.13 ± 48.75 to 101.38 ± 32.39 (p = NS). After 6 months, all bone mineral parameters were similar to baseline levels; however, slightly higher calcium-based phosphate binders were prescribed. Lowering calcium content from 1.75 mmol/L to 1.25 mmol/L in PD fluids in patients on icodextrin resulted in stable calcium values, a temporal increase in iPTH and a modest increase in calcium-based phosphate binder prescription. Using icodextrin for the long once-daily dwell appears to attenuate the effects on bone mineral parameters when lowering the calcium concentration of the short dwells. [ABSTRACT FROM AUTHOR]

The article is devoted to the production and research of composite heat-insulating porous ceramics based on common and available local raw materials in the form of perlite, expanded clay, kaolinite clays using phosphate binders. Experimental samples were obtained by semi-dry pressing and ramming, followed by heat treatment at temperatures from 600 °C to 1100 °C. The processes of structure formation occurring in the compositions during heating are characterized by X-ray diffraction and local X-ray microanalysis. The obtained results showed the formation of the crystal structure of alumophosphate AlPO4 in the form of tridimite and cristobalite in the filler grains, and calcium phosphate Ca3(PO4)2 in the binding matrix of the composite. Heating temperature increase to 1150 °C lead to an increase in the amount of melt in the areas with the largest number of impurity elements. The influence of formation methods and technological parameters on shrinkage processes, density and strength of phosphate-bonded specimens has been demonstrated. The analysis of experimental results showed that the samples containing filler (expanded perlite), clay (secondary Samarkand kaolin) and orthophosphoric acid (40 wt%) are optimal in combination of density, thermal conductivity and resistance to high temperatures.

The design of the measuring circuit of a system of structural health monitoring of objects based on a piezosensitive matrix is presented. It is shown that a promising trend in the design of matrices of bulk piezosensitive materials and piezocoatings is the possibility of using phosphate binders. The proposed structure of a piezocoating based on a phosphate binder consists of five alternately formed layers. The piezoelectric layer is formed at a temperature from 10 to 30°C with subsequent polarization for 3 h at an electrical voltage of no more than 300 V and a temperature of no more than 120°C. The dielectric and piezoelectric characteristics of the piezocomposite samples formed from a piezoelectric material similar to PZT-19 and a phosphate binder in the mass ratio of 10 : 1 are presented. Polarized samples are subjected to artificial aging by exposure at a temperature of 80°C for 10 days, after which piezosensitivities d33 and d31 and relative dielectric permittivity are measured. In addition, a technique is developed to estimate the critical number of cycles of switching the polarity of the electric field applied to a thin-film sample made of a ceramic dielectric. The technique is based on approximation of the dependence of the residual polarization on the number of cycles of switching the polarity of the electric field applied to the sample. This makes it possible to predict the deviation of the dielectric properties of the sample material from the required values. The results of the full-scale experiment confirmed the possibility of creating a piezoelectric material based on a phosphate binder for the fabrication of sensitive elements of the structural health monitoring systems. [ABSTRACT FROM AUTHOR]

Background: Hyperphosphatemia is linked to increased mortality and morbidity in patients on hemodialysis. Currently, the phosphate intake and dialytic removal in predominantly vegetarian patients on twice-weekly dialysis is not well studied. Materials and Methods: This prospective, study recruited patients on twice-weekly dialysis of at least 3 months duration. Baseline clinical variables were measured. Dietary protein and phosphorus intake was assessed using a validated food frequency questionnaire. Phosphate binder use was assessed, hourly blood was collected for serum phosphorus during dialysis, and spent dialysate was collected to estimate cumulative phosphorus removal during the session. Results: Forty (67%) of the 60 patients studied were vegetarians. Twenty-eight (48%) were hyperphosphatemic, and 15 (25%) had serum parathormone (PTH) >500 pg/ml. The mean phosphorus intake was 1247 (±312) mg/day, the mean serum phosphorus was 5.49 (±2.01) mg/dl, and the mean dialytic phosphorus removal was 910 (±383) mg/session. Up to 67% of the study population took calcium-based phosphate binders, 25% took sevelamer carbonate, and 40% took activated vitamin D preparation. The lowest tertiles of phosphorus intake correlated with low energy-adjusted protein intake and hypoalbuminemia. Hyperphosphatemic subjects had better nutritional indices (mid-upper arm circumference and body mass index). Dietary intake and serum phosphorus levels were not mutually associated, but both were strongly correlated with total phosphorus removal in the spent dialysate. Serum phosphorus levels fell by 32% by the first hour of hemodialysis. Conclusion: Twice-weekly dialysis is often practised in resource-limited Asian countries. However, due to a predominantly vegetarian diet, hyperphosphatemia was noted only in up to half of the patients, despite twice-weekly hemodialysis schedules. This reinforces the fact that plant-based dietary phosphate is less well absorbed. [ABSTRACT FROM AUTHOR]

Introduction: Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients. Methods: Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly. Results: The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, p < 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5–7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups. Conclusion: There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels. [ABSTRACT FROM AUTHOR]

Background: Phosphate binders cause high pill burden for dialysis patients, complicate medication regimens, and have unpleasant taste and large size which may affect patients' quality of life. This study explores the association between phosphate binder pill burden and health‐related quality of life (HRQoL) in dialysis patients. Methods: We conducted a cross‐sectional multi‐centre cohort study in 21 Dutch dialysis centres. Phosphate binder pill burden was extracted from electronic patient records. Primary outcome was HRQoL measured with the Short Form 12 physical and mental component summary scores (PCS and MCS). Secondary endpoints were severity of gastro‐intestinal symptoms, itching, dry mouth, and mental health symptoms, measured with the Dialysis Symptom Index. Results: Of 388 included patients, aged 62 ± 16 years, 77% underwent haemodialysis. PCS scores were comparable for patients with and without phosphate binders. Patients using 1–3 pills reported lower scores for decreased appetite (β −0.5; 95%CI −0.9 to −0.2), implying better appetite, than patients without phosphate binders. Patients using 4–6 pills also reported lower scores for decreased appetite (β −0.5; 95%CI −0.8 to −0.1) and for itching (β −0.5; 95%CI −0.9 to −0.1). Patients using >6 pills reported lower MCS (β −2.9; 95%CI −6.2–0.4) and higher scores for feeling nervous (β 0.6; 95%CI 0.1–1.1) and feeling sad (β 0.4; 95%CI 0.0–0.9). Conclusion: Phosphate binder pill burden is not associated with physical quality of life. A higher pill burden is associated with better appetite and less itching. Patients using >6 pills per day report lower mental quality of life and felt nervous and sad more often. Summary at a glance: This cross‐sectional cohort study assessed the impact of phosphate binders on quality of life in dialysis patients. A higher phosphate binder pill burden was associated with worse mental quality of life, more severe feelings of nervousness and sadness, a better appetite, and less severe feelings of itching but not with physical quality of life. [ABSTRACT FROM AUTHOR]

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

BackgroundA database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care.MethodsAdult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL.ResultsAt baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001).ConclusionAmong PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed.

Phosphate absorption occurs in the gastrointestinal tract through paracellular absorption and transcellular transport. The paracellular pathway does not saturate and has a significantly higher absorption capacity than does the transcellular pathway. Evidence indicates that this pathway is the primary mechanism of intestinal phosphate absorption, particularly with Western diets containing high amounts of phosphorus. Elevated serum phosphorus concentrations are associated with cardiovascular morbidity and mortality but serum phosphorus concentrations > 5.5 mg/dL are highly prevalent despite best efforts with dietary phosphate restriction, dialysis, and the use of phosphate binders. The efficacy of phosphate binders may be inherently limited because the mechanism of action does not target any phosphate absorption pathway. Thus, therapeutic innovations are needed to address the limitations of phosphate binders. Novel therapies leveraging new mechanistic understandings of phosphate absorption and the primacy of the paracellular pathway may improve phosphate control. Phosphate absorption inhibitors that target the pathway are a novel therapeutic class. Tenapanor is an investigational first-in-class nonbinder phosphate absorption inhibitor that inhibits the sodium-hydrogen exchanger isoform 3 to reduce paracellular permeability specific to phosphate. Phosphate absorption inhibitors may represent a new mechanistic approach to phosphate management with the potential to improve clinical outcomes.

Objective: To ascertain the efficacy of Sevelamer Carbonate as a better phosphate binder for controlling mineral bone disease biochemical parameters in dialysis patients of a tertiary care centre compared to calcium acetate. Study Design: Prospective Quasi-experimental study. Place and duration of the study: Dialysis unit of Pakistan Emirates Military Hospital Rawalpindi Pakistan from Aug to Dec 2020. Methodology: The sample population comprised 91 patients undergoing maintenance thrice weekly haemodialysis patients treated with Sevelamer Carbonate or Calcium Acetate. CKD-MBD was assessed by serum calcium, phosphorus, ALP, albumin and PTH at the start of the study and then at the end of three months after being treated with phosphate binders. Results: Both Groups had reduced serum phosphorus significantly from baseline to 12 weeks but Sevelamer slightly more than calcium acetate. (Group-1 from 6.90±1.35 to 5.10±1.21, while Group-2 from 7.00±1.31 to 5.90±1.48). The mean Calcium x Phosphorus product was also significantly reduced (p<0.005), decreases after 12 weeks, with 50.0 ± 16.0 in the Sevelamer Hydrochloride Group and insignificantly reduced (52.20±5.20mg2/dl) in the calcium acetate Group. The mean serum calcium increased significantly in the calcium acetate Group from 9.55±0.47 to 10.50±0.90) p=0.003 but was unchanged in the Sevelamer hydrochloride Group (9.56±0.60 to 9.57±0.67; p=0.94). Conclusions: CKD-MBD and its sequelae need special medication, and early detection of biochemical abnormalities and timely intervention with phosphate lowering therapy can abridge the disease burden, thus revamping the quality of life and ultimately abatement of cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

Purpose: It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Methods: Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Results: Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. Conclusion: These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients. [ABSTRACT FROM AUTHOR]

Michel Vallée,1 Jordan Weinstein,2 Marisa Battistella,3 Roxanne Papineau,4 Dianne Moseley,5 Gordon Wong6 1Université de Montréal - Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada; 2Division of Nephrology, St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada; 3University Health Network- Toronto General Hospital, Toronto, Ontario, Canada; 4Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Québec, Canada; 5Trillium Health Partners, Mississauga, Ontario, Canada; 6Trillium Health Partners, Credit Valley Nephrology, Mississauga, Ontario, CanadaCorrespondence: Gordon WongTrillium Health Partners, Credit Valley Nephrology, 2300 Eglinton Ave. West Suite #501, Mississauga, Ontario, L5M 2V8, CanadaEmail gwong1030@gmail.comAbstract: Population-based studies have shown that most patients with advanced chronic kidney disease (CKD) do not have optimal phosphate levels. Meta-analyses suggest that there is a morbidity and mortality benefit associated with the lowering of serum phosphate levels. However, to date there is no conclusive evidence from randomized controlled trials (RCTs) that lowering serum phosphate levels reduces the risk of morbidity and mortality. However, hyperphosphatemia may pose a risk to patients and treatment should be considered. We therefore sought to conduct a multidisciplinary review to help guide clinical decision-making pending results of ongoing RCTs. Restricting dietary phosphate intake is frequently the first step in the management of hyperphosphatemia. Important considerations when proposing dietary restriction include the patient’s socioeconomic status, lifestyle, dietary preferences, comorbidities, and nutritional status. While dietary phosphate restriction may be a valid strategy in certain patients, serum phosphate reductions achieved solely by limiting dietary intake are modest and should be considered in conjunction with other interventions. Conventional dialysis is also typically insufficient; however phosphate removal may be augmented by increased frequency or duration of dialysis, or through enhanced methods such as hemodiafiltration. Phosphate binders have been shown to reduce absorption of dietary phosphate and lower serum phosphate levels. There are several phosphate binders available, and while they all lower phosphate levels to variable degrees, they differ with respect to their pill burden, potential to induce or exacerbate vascular calcification or ectopic calcification, tissue accumulation, safety, and tolerability. The widespread treatment of hyperphosphatemia requires convincing data from RCTs to ascertain whether lowering serum phosphate levels improves patient-important outcomes, as well as the optimal method and degree of phosphate control. In the interim, the decision and approach used to treat hyperphosphatemia should be based on the best available data, as well as patient needs and clinical judgment.Keywords: chronic kidney disease, nutrition, phosphate, phosphate binders

Aim: The incidences of osteoporosis, fracture and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD‐mineral bone disease (CKD‐MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in haemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD‐MBD. Methods: We conducted a prospective cohort of 65 haemodialysis patients to investigate the effect of 12‐month monotherapy of phosphate binders composing calcium‐based phosphate binders (CPB) or non‐calcium‐based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. Results: When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1N‐terminal propeptide (P1NP), bone‐specific alkaline phosphatase (BALP), and tartrate‐resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in haemodialysis patients. Conclusion: Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in haemodialysis patients who already had low BMD. P1NP, BALP and TRAP5b could be used to guide the appropriate management, including anti‐resorptive and anabolic medications, and predict low BMD in haemodialysis patients treated with phosphate binders. SUMMARY AT A GLANCE: The effect of phosphate binders on bone biomarkers and bone mineral density (BMD) in haemodialysis patients is unestablished. This prospective study revealed that non‐calcium‐based phosphate binders were associated with higher bone turnover biomarkers compared with calcium‐based phosphate binders. Diagnostic power of each bone biomarker for low BMD was demonstrated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. Methods: Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. Results: We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. Conclusion: The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients. [ABSTRACT FROM AUTHOR]

Patients with kidney failure and early stages of chronic kidney disease often develop hyperphosphatemia, which is associated with negative outcomes. The reduction of phosphate levels is the established clinical practice. However, achieving and maintaining target phosphate levels is challenging, and the current methods of phosphate management lead to poor quality of life (QoL) in patients receiving dialysis, particularly because patients might not receive adequate education on phosphate control. Patients receiving dialysis are advised to maintain stringent dietary restrictions and might experience anxiety and depression due to the constant burden of dietary self-management. The lack of nutritional information on food labels makes adhering to dietary restrictions even more confusing and difficult. Phosphate binders are the only pharmacologic treatment currently indicated for hyperphosphatemia. However, phosphate binders have a limited binding capacity and are difficult to incorporate into patients’ daily routines. Because of the suboptimal efficacy of phosphate binders and the negative impact of dietary restrictions on patient QoL, novel therapies for more effective phosphate control are needed. New treatment options that control phosphate levels would enable patients to eat a more normal, healthy diet and potentially improve their QoL.

Resumen: Introducción: Las alteraciones del metabolismo óseo y mineral son muy frecuentes en la enfermedad renal crónica (ERC). El aumento en los niveles de fósforo condiciona enfermedad ósea, riego de calcificación y mayor mortalidad, por lo que cualquier estrategia encaminada a su reducción debe ser bienvenida. El último fármaco incorporado al arsenal terapéutico para tratar la hiperfosforemia en la ERC es el oxihidróxido sucroférrico (OSF). Objetivo: Analizar la eficacia y seguridad de OSF en 3 cohortes de pacientes, una con ERC avanzada no en diálisis, otra en diálisis peritoneal y finalmente otra en hemodiálisis, seguidas durante 6 meses. Métodos: Estudio observacional multicéntrico, prospectivo, de práctica clínica. Se analizaron variables clínicas y epidemiológicas. Se valoró la evolución de parámetros relacionados con las alteraciones del metabolismo óseo y mineral y la anemia. Resultados: Se incluyeron en el estudio 85 pacientes (62 ± 12 años, 64% varones, 34% diabéticos), 25 con ERC avanzada no en diálisis, 25 en diálisis peritoneal y finalmente 35 en hemodiálisis. En 66 pacientes (78%) OSF fue el primer captor del fósforo; en los otros 19 se sustituyó un captor previo por OSF, por falta de tolerancia o eficacia. La dosis inicial de OSF fue 964 ± 323 mg/día. Globalmente los niveles séricos de fósforo experimentaron un descenso significativo a los 3 meses de tratamiento (19,6%; p

Spent biochar is produced after adsorption of heavy metal which is hazardous by nature. A suitable disposal technique is required to prevent the leaching of heavy metals from spent biochar into the environment. This study highlights the solidification and stabilization (S/S) of copper loaded spent pine-cone biochar by chemically bonded phosphate cement (CBPC). The response surface methodology (RSM) was used to conduct S/S experiments in order to evaluate the compressive strength of CBPC products. The CBPC samples were prepared by varying biochar content (5-50 wt. %); W:S (0.15-0.3) and curing time(3-28d). Results illustrated that CBPC products containing biochar had higher compressive strength upto 12.8 MPa in comparison to CBPC without biochar i.e., upto 10.8 MPa. XRD and SEM analysis confirmed the presence of K-struvite (MgKPO4.6H2O), copper containing phases (Ca-Cu-Si), copper phosphate precipitates (Cu3(PO4)2) and filling of pore spaces by spent biochar. Highest compressive strength of 12.8 MPa was obtained at an optimized biochar content of 25%, W:S of 0.18 and curing time of 28 d. The evaluation of leaching potential by TCLP illustrated that stabilization of Cu (II) upto 99.9% was achieved in CBPC product. The risk assessment study revealed that there is no significant danger due to leaching of heavy metals from final CBPC product indicating that it can be readily disposed in the hazardous landfill sites.

Mineral-bone disorder in chronic kidney disease (CKD-MBD) is one of the most important factor determining prognosis in dialysis patients. CKD-MBD syndrome occurs at the CKD stage 2 and reaches its maximum in patients with end-stage renal disease. Currently, hyperphosphatemia plays a central role in the pathogenesis of CKD-MBD(the so-called “phosphate-centric paradigm”). In turn, hyperphosatemia leads to an increase in the level of phosphaturic hormone - fibroblast growth factor type 23 (FGF23). FGF23 causes remodeling and fibrosis of the myocardium, renal parenchyma, the development of calcification and vascular atherosclerosis. Thus, hyperphosphatemia, indirectly, through an increase in the level of FGF23, is one of the most important manifestation of progressive CKD and a significant factor of high overall and cardiovascular morbidity and mortality in this cohort of patients. Given that cardiovascular events are the main cause of mortality in patients on renal replacement therapy with dialysis, correction of hyperphosphatemia is a prerequisite for successful monitoring of this group of patients and influencing prognosis. The review presents the main approaches for the correction of hyperphosphatemia in CKD, such as nutritional correction, modification of dialysis methods, and prescribing of phosphate binders. The advantages of calcium-free phosphate-binding agents are considered in details and had compared with effects of containing calcium phosphate binders.The treatment of hyperphosphatemia should be approached comprehensively, using optimal dialysis therapy regimens, training and monitoring dietary phosphate consumption with the obligatory use of phosphate binders that are most effective and well tolerated.

Aims: 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.Materials and Methods: 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.Results: 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.Limitations: 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.Conclusion: SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia in patients with chronic kidney disease (CKD) is an important complication of impaired renal function and is associated with negative clinical consequences such as cardiovascular calcification, bone disease and secondary hyperparathyroidism, which leads to a worsening of cardiovascular di­sease and mortality. The purpose of this review was to discuss the management of hyperphosphatemia in CKD. The following topics are considered: phosphorus homeostasis, diagnosis of hyperphosphatemia, the effectiveness of modern dietary and pharmacological treatment using phosphate binders.

Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 9), while a dosage of 700 ± 230 mg/day only decreased it by −3% in the presence of a PPI (n = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 7, FCH: 571 ± 189 mg/day) and by −17% in the presence of a PPI (n = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was −7% in the absence of a PPI (n = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by −13% in the presence of a PPI (n = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

Abstract Background Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. Methods For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2–8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. Results In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. Conclusions These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Background Hemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates. Methods Adult HD patients in Germany, Italy, Spain and the UK in the Dialysis Outcomes and Practice Patterns Study were administered a survey instrument in late 2017. Patients were asked about their satisfaction with their PBs, as measured through three questions (difficulty, inconvenience and dissatisfaction) on a 5-point Likert scale, with each dichotomized into average worst versus good responses. These were used as predictors in linear regression models of continuous serum phosphorus levels and in Cox proportional hazards models of mortality, with adjustments for demographics, comorbidities and laboratory values. Results Patients having greater difficulty, inconvenience and dissatisfaction with their PB had higher serum phosphorus levels in adjusted models {+0.21 mg/dL [95% confidence interval (CI) ±0.23], +0.30 (±0.21) and 0.36 (±0.22), respectively}, and higher odds of having serum phosphorus levels ≥6.0 mg/dL. Measures of dissatisfaction were also associated with an elevated risk of mortality, with adjusted hazard ratios of 2.2 (95% CI 1.3–3.6), 1.6 (1.0–2.6) and 1.7 (1.1–2.7), respectively; this association was not strongly affected by adjustment for baseline serum phosphorous level. Conclusions Self-reported difficulty, inconvenience and dissatisfaction in taking one's prescribed PBs were associated with elevated serum phosphorus levels and serum phosphorus levels above clinically meaningful thresholds. While the mechanism for the association with mortality is unclear, patient-reported satisfaction should be considered when attempting to manage patient serum phosphorus levels. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients.Methods: Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income.Results: A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively.Conclusions: Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs. [ABSTRACT FROM AUTHOR]

Elevated serum phosphorus levels are common in patients with chronic kidney disease and are associated with heart and vascular disease, conditions that in turn are associated with increased mortality. Accurately managing phosphorus intake by restricting dietary protein alone can prove challenging because protein from different sources can contain varying amounts of available phosphorus. Additives used in processed foods frequently are high in inorganic phosphorus, which is readily absorbed, compounding this difficulty. Recent evidence suggests that dietary protein restriction in some cases may do more harm than good in some patients treated with maintenance hemodialysis because protein restriction can lead to protein-energy wasting, which is associated with increased mortality. Accordingly, phosphorus binders are important for managing hyperphosphatemia in dialysis patients. Managing hyperphosphatemia in patients with late-stage chronic kidney disease requires an individualized approach, involving a combination of adequate dietary advice, phosphate-binder use, and adjustments to dialysis prescription. We speculate that increased use of phosphate binders could allow patients to eat more protein-rich foods and that communicating this to patients might increase their perception of their need for phosphate binders, providing an incentive to improve adherence. The aim of this review is to discuss the challenges involved in maintaining adequate nutrition while controlling phosphorus levels in patients on maintenance hemodialysis therapy.

Objective: Hyperphosphatemia in end-stage renal disease (ESRD) is associated with many serious patient-level consequences including cardiovascular events and mortality. The purpose of this study was to investigate the use of phosphate binders in ESRD patients on maintenance hemodialysis. Materials and Methods: The study was a prospective observational cohort study including adult ESRD patients undergoing hemodialysis at a secondary hospital in United Arab Emirates. Patient characteristics were compared as per type of phosphate binder used. Bivariate and multivariate multinomial logistic regression analyses were carried out to determine variables that were independently associated with use of different phosphate binders. Results: Phosphate binders used at our study site were sevelamer, calcium carbonate, and a combination of sevelamer and calcium carbonate. Bivariate multinomial logistic regression analysis revealed that serum phosphorous (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.04–1.09, P = 0.047; OR: 0.10, 95% CI: 0.03–0.89, P = 0.042), calcium (OR: 0.11, 95% CI: 0.02–0.86, P = 0.041; OR: 0.22, 95% CI: 0.01–0.96, P = 0.012), and calcium–phosphorous product (OR: 0.20, 95% CI: 0.06–0.64, P = 0.008; OR: 0.16, 95% CI: 0.05–0.54, P = 0.003) levels were significantly lower in patients on sevelamer per se as well as in patients on combination therapy, respectively when compared to calcium carbonate per se. Multivariate multinomial logistic regression analysis revealed that in sevelamer and combination groups, cardiovascular diseases (OR: 0.12, 95% CI: 0.02–0.65, P = 0.022; OR: 0.10, 95% CI: 0.01–0.88, P = 0.038) were significantly lesser compared to calcium carbonate group after being adjusted for other variables in the model. Conclusion: We observed that hyperphosphatemia and related events in our study population were better controlled by sevelamer per se and combination therapy than calcium carbonate per se. Further large scale, multicenter studies are required to confirm and establish these findings.