Phosphate Binders Research Articles

Tenapanor-A Novel Approach for Management of Hyperphosphatemia in End Stage Renal Disease: A Clinical Study Aggregate Review

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.
 Keywords: Tenapanor, phosphate binding agents, hyperphosphatemia, chronic kidney disease, phosphate control, phosphate binders, phosphate absorption, phosphate absorbtion inhibitor.

Clinical characteristics and treatment modalities in uremic and non uremic calciphylaxis - a dermatological single-center experience

Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% (n = 53), followed by the thigh and gluteal regions in 7% (n = 4). Significant differences were identified in comorbidities, such as atrial fibrillation (p < 0.001) and hyperparathyroidism (p < 0.01) accounting for CUA patients. Medication with vitamin K antagonists (p < 0.001), phosphate binders (p < 0.001), and loop diuretics (p < 0.01) was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (p < 0.001), increased parathyroid hormone (p < 0.01) and triglyceride levels (p < 0.01), hypoalbuminemia (p < 0.01) and decreased hemoglobin values (p < 0.001) in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% (n = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.

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

Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.

Effects of the novel sodium-dependent phosphate cotransporter 2b inhibitor DZ1462 on hyperphosphatemia in chronic kidney disease.

Serum phosphate levels remain insufficiently controlled in chronic kidney disease (CKD) patients, and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate cotransporter type 2b (NPT2b) holds promise as one such strategy. The in vitro cellular potency of DZ1462 was evaluated using a radioactive Pi uptake assay on stable Chinese hamster ovary (CHO) cell clones transfected with human NPT2b (hNPT2b) or rat NPT2b (rNPT2b). The ability of DZ1462 to inhibit phosphate absorption was studied in vivo in an acute model after oral bolus challenge with 33PO4 and in an adenine-induced chronic hyperphosphatemia rat model. PK and minitox was also evaluated. The cellular assays with the hNPT2b-CHO and rNPT2b-CHO clones showed that DZ1462 significantly and potently inhibited phosphate uptake. In vivo, in a chronic Pi-fed rat model, DZ1462 effectively inhibited intestinal Pi uptake. In a hyperphosphatemia rat model, DZ1462 significantly inhibited Pi uptake, and DZ1462 in combination with sevelamer had a synergistic effect. The pharmacokinetics (PK) study confirmed that DZ1462 is a gastrointestinal (GI)-restricted compound that can remain in the intestine for a sufficient duration. In addition, DZ1462 also reduced cardiovascular events and ameliorated osteoporosis in a CKD animal model. This study revealed that a GI-restricted NPT2b inhibitor DZ1462 potently inhibits NPT2b in vitro and blocks intestinal phosphate uptake in multiple animal models with potential to reduce various cardiovascular events in CKD models. Therefore, DZ1462 may be useful to treat renal disease patients who have shown an unsatisfactory response to phosphate binders.

Features of Hardening of Aluminosilicophosphate Binder in Cellular Concrete

Cellular phosphate concretes are used as an insulating material for some high-temperature aggregates due to their high temperature resistance, fire resistance and residual strength at the level of values after drying. The use of industrial waste in phosphate cellular concrete technology made it possible to improve some properties without reducing the application temperature. The paper shows that dispersed aluminosilicate waste from refractory production has sufficient activity (porization ability) to obtain a phosphate binder. The features of the hardening of an aluminosilicophosphate binder cured with dispersed metallic aluminum have been studied; the change in the phase composition of the cured binder after firing at different temperatures has been studied by differential thermal and X-ray phase analysis. It has been established that the developed aluminosilicophosphate binder makes it possible to obtain fireclay cellular concrete with an application temperature of up to 1400оC. A comparison of the changes in the phase composition for the developed aluminosilicophosphate composition and a pure aluminophosphate binder is performed. A shift in the temperature of the processes is noted in an upward direction for the aluminosilicophosphate binder, which is explained by the fact that silicon ions do not form independent phosphate compounds, but are embedded in the crystal lattice of aluminophosphates, changing their properties and shifting the intervals of phase transitions.

Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor.

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.

The effectiveness of feed additives in chronic kidney disease in cats

Chronic kidney disease in cats is one of the most common diseases. The main direction of palliative therapy for chronic kidney disease and extending the survival time of cats is to limit phosphates in the diet and normalize the phosphorus content in the animal’s body. In order to reduce phosphates, phosphate binders are used - substances whose mechanism of action is to bind excess phosphate ions in the gastrointestinal tract, which prevents their entry into the blood-stream. The purpose of the study is to analyze the effectiveness of feed additives “Urdetox” and “Ipakitine” in a comparative aspect in the palliative treatment of chronic kidney disease in cats. Determination of the biological activity of the proposed feed additive for cats with CKD in the form of tablets was carried out on the basis of veterinary clinics in the city. Volgograd, St. Petersburg, Moscow, in the period 2021-2022. The objects of the study were cats whose owners complained of loss of animal body weight, often a general depressed state, decreased appetite, periodic vomiting, frequent urination, dull hair. The diagnosis and experiment were carried out by collecting anamnestic data, determining clinical signs and laboratory data - a general urine test and a biochemical analysis of blood serum. Studies have shown that feed additives containing a phosphate binder and a detoxicant help eliminate the main clinical manifestations of chronic renal failure. The introduction of the essential amino acid -taurine into the feed additive in the form of Urdetox tablets, as well as the accuracy of dosing and ease of use increase the effectiveness of its biological action.

Sex-dependent differences in patients treated with regular hemodialysis

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Introduction.&amp;lt;/strong&amp;gt; The aims of the study were to find out sex differences among patients starting regular hemodialysis (HD) in 2014 and to check whether these differences change over a five-year period.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Methods.&amp;lt;/strong&amp;gt; The retrospective five-year study included 35 patients (24 men; 11 women) starting HD in HD centers in Leskovac and Pirot in 2014. Demographic data, clinical data, laboratory findings, and medication used for examined patients were taken from medical records.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Results.&amp;lt;/strong&amp;gt; A comparison of patients of different sexes at the beginning of the study showed that women were significantly older (70.55 &amp;amp;plusmn; 13.27 vs. 58.88 &amp;amp;plusmn; 15.27 years), but diabetes and hypertension were more frequent causes of chronic kidney disease in men. Women had significantly lower body mass index and serum creatinine level than men in the first year of the study. During all five years, the HD adequacy index spKt/V was higher in women than in men, but the difference reached statistical significance only in the third year (1.4 &amp;amp;plusmn; 0.2 vs. 1.2 &amp;amp;plusmn; 0.2). Serum iPTH level was higher in women than in men in almost the entire study period. There was no significant sex difference in blood pressure, type of vascular access, number of HD hours per week, in the percentage of patients who used erythropoiesis-stimulating agents or phosphate binders. During the study period 10 (42.7%) men and five (45.5%) women died and the most frequent causes of death were cerebrovascular and cardiovascular diseases.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Conclusion. &amp;lt;/strong&amp;gt;The study revealed several differences between men and women on regular HD, but no treatment inequality was found.&amp;amp;nbsp;&amp;lt;/p&amp;gt;

A comparative analysis of serum phosphorus levels and mineral metabolic markers in non-dialysis and dialysis chronic kidney disease patient: a cross-sectional study

Background: Chronic kidney disease is a major public health problem worldwide. As kidney function declines, it leads to several metabolic abnormalities including dysregulation of mineral metabolism. It is also reported that hyperphosphatemia in patients with advanced kidney disease is associated with an increased risk of mortality and cardiovascular events, and is higher in dialysis-dependent chronic kidney disease (CKD) patients compared to non-dialysis CKD. However, data in the Indian context is limited. Objectives were to evaluate and compare serum phosphorus levels and associated factors in non-dialysis and dialysis CKD patients. Also, the impact of dietary phosphate restriction and the use of phosphate binders on serum phosphorus is analysed. Methods: A cross-sectional study was conducted at a tertiary care hospital in Kolkata, India, with 100 CKD patients: 50 non-dialysis CKD patients and 50 dialysis-dependent CKD patients. Relevant demographic, clinical and laboratory parameters including serum phosphorus, calcium, parathyroid hormone (PTH), alkaline phosphatase, albumin and estimated glomerular filtration rate (eGFR) were collected. Data was analyzed using appropriate statistical tests. Results: Mean serum phosphorus was significantly higher in the dialysis CKD group (6.12±0.34 mg/dl) compared to the non-dialysis CKD group (4.56±0.80 mg/dl). Serum calcium and PTH were also higher while eGFR and albumin were lower in the dialysis CKD group. Serum phosphorus levels increased with advancing CKD stages in the non-dialysis group. Phosphate binder helped phosphorus control in dialysis CKD patients. Conclusions: Our study is in confluence with other reports and dietary phosphate restriction and the use of phosphate binders help optimize phosphorus levels in CKD patients.

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

Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis. We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year. The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p &lt; 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p &lt; 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p &lt; 0.0001 vs. baseline). Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.

Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis.

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

Tertiary Hyperparathyroidism Presenting as Multifocal Brown Tumors: A Case Report

Brown Tumor (BT) of the bone is a rare manifestation of hyperparathyroidism (HPTH), an unusual reactive bone lesion attributed to disturbed bone remodeling, from long-standing increase in parathyroid hormone level (PTH). Historically, BTs were described with primary HPTH but due to early diagnosis of this entity, and improved survival in patients with end-stage renal disease (ESRD) especially those on renal replacement therapy (RRT), more cases of BT are now described in this population, and less in PHPTH. Thus, it is mostly the consequence of untreated secondary or tertiary HPTH whose major culprits are chronic kidney disease (CKD) and ESRD. The management of brown tumors related to chronic renal failure consists primarily of its prevention through the use of phosphate binders, vitamin D analogues, and calcimimetics with surgical parathyroidectomy reserved as the final resort in refractory cases. Herein, we present the case of a 24-year-old female patient with ESRD on intermittent hemodialysis (IHD) who developed recent onset facial tumefaction. Blood work revealed markedly elevated PTH at more than 5000 pg/ml, upper borderline hypercalcemia, and hyperphosphatemia. Further investigations with chest computed tomography (CT) and Technetium-99m (99mTc)- Sestamibi scan nuclear imaging showed multiple ribs lytic lesions as well as features of extensive BT and parathyroid adenomas. Thereafter, the patient was sent for parathyroidectomy after which the patient developed hungry bone syndrome.

Risk factors for arteriovenous fistula dysfunction in hemodialysis patients: a retrospective study

Arteriovenous fistula (AVF) is the first choice of vascular access in hemodialysis (HD) patients. However, the correlations between patient factors and the arteriovenous fistula patency remain unclear. Therefore, our study investigates the risk factors associated with AVF dysfunction in HD patients. A total of 233 end-stage renal disease (ESDR) patients who met the study inclusion criteria in the Nephrology Department of Hunan Provincial People’s Hospital between December 2020 and June 2022 were included in this study. The baseline demographic, clinical and laboratory parameters were collected at the time of AVF creation and analyzed. Of the 233 ESRD patients, 146 (62.7%) were male and the mean age was 56.11 ± 12.14 (21–82) years. The patients were followed for a median time of 14 months. Kaplan–Meier analysis showed a 6-, 12- and 24-month post-placement survival of 87.1%, 82.8% and 80.7%, respectively. Univariate Cox regression analysis revealed weight (HR, 1.03; P = 0.03) as a predictor for the loss of vascular access functionality. In addition, multivariate Cox regression analysis further demonstrated that sex (HR, 3.41; P = 0.03), weight (HR 1.08; P < 0.01) and phosphorus level (HR: 3.03; P = 0.01) are independent risk factors for AVF dysfunction. AVF dysfunction is highly associated with several risk factors including weight, phosphorus level, and sex. Positive intervention strategies targeting these potential factors, such as weight loss or oral phosphate binders could improve the long-term success of AVF.

Hemodialysis in Brazil: differences across geographic regions regarding demographics, laboratory parameters and drug prescription.

Brazil has a vast territory divided into five geographic regions with important differences in sociodemographic indices. We aimed to present and compare socio-demographic characteristics, biochemical results, and drug prescription of patients on chronic hemodialysis (HD) treatment in the five geographic regions. We evaluated data from the Brazilian Dialysis Registry of all adult patients undergoing chronic HD in 2021. Variables included sociodemographic characteristics, serum levels of phosphate, calcium, and albumin, hemoglobin, urea reduction rate, and prescription of phosphate binders, erythropoietin, and intravenous iron. Data from the North and Northeast regions were combined into one group. A total of 13,792 patients (57.9 ± 16.0 years old, 58.5% male, median HD vintage of 31 (11-66) months) from 73 dialysis centers were analyzed. Regional distribution was 59.5% in the Southeast; 21.7% in the South; 5.9% in the Midwest; and 12.9% in the North/Northeast. Sociodemographic features, biochemical results, and medication prescriptions differed across regions. The prevalence of elderly patients was lower in the Midwest and North/Northeast. The South region had the highest prevalence of hyperphosphatemia (41.2%) and urea reduction rate <65% (24.8%), while anemia and hypoalbuminemia were more prevalent in the Southeast, 32.7% and 11.6%, respectively. We found differences in socio-demographics, clinical features, and drug prescriptions across Brazilian geographic regions. Some findings reflect the socio-demographic diversity of the country, while others deserve further elucidation.

Deposition of Sevelamer crystals in gastrointestinal tract and lung parenchyma: A rare autopsy finding

Abstract Introduction/Objective Sevelamer carbonate is a non-calcium-based phosphate binder used for the management of hyperphosphatemia in patients with end stage renal disease. The well-known side effects of sevelamer include nausea, vomiting and abdominal pain. However, there are few case reports which described the deposition of sevelamer crystals in the gastrointestinal tract causing mucosal injury, pseudotumor or obstruction. Methods/Case Report We hereby present a case of a 43-year-old decedent female with past medical history of seizures, hypertension, cocaine use, type B aortic dissection status post thoracic endovascular aortic repair, total arch replacement, reconstruction of innominate, carotid, and subclavian artery who presented with hematochezia concerning for possible aorto-esophageal fistula on 10/06/2022 and acute kidney injury. Imaging showed a thrombus in mid-esophagus, blood in trachea and narrowing of the left main stem bronchus. Labs revealed worsening of BUN and creatinine and up trending hyperphosphatemia and therefore sevelamer carbonate via nasogastric route was started on 10/13/22. Unfortunately, the patient’s hospital course was complicated, and she passed away on 11/14/2022. At autopsy, the deceased had gross evidence of acute lung injury with diffuse alveolar hemorrhage, aorta-bronchial ruptured aneurysm defect and aorto-esophageal fistulas. On histopathological examination, the stomach, small and large bowel showed autolysis, necrosis, and numerous rectangular shaped, non-polarizable crystals. The crystals with characteristic morphology of “fish scale” with hues of pink in the center and yellow to orange in the periphery were identified as sevelamer crystals. Interestingly, crystal deposition was also identified in lung parenchyma and rarely in aortic wall and the fistula. Results (if a Case Study enter NA) NA Conclusion As one of the more commonly used resins in end stage kidney disease, gastrointestinal adverse effect of sevelamer carbonate is often underrecognized. Our case report heightens the awareness of the characteristic morphology of this biologically inert agent, sevelamer to those who are unaware of their morphology. This case also highlights the adverse effect of sevelamer in all patients presenting with gastrointestinal symptoms, such as gastrointestinal bleeding and abdominal pain with the use of sevelamer.

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

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

Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial

BackgroundTenapanor is a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis.MethodsThis phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5–7.0 mg/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint.ResultsOf the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was − 1.18 mg/dL (95% confidence interval: − 1.54, − 0.81 mg/dL) with tenapanor. From a baseline value of 7.65 mg/dL, serum phosphorus decreased to 6.14 and 5.44 mg/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5–6.0 mg/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%.ConclusionsAdministration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable.Trial registrationNCT04766385.

Ion Chromatography Study of Ca/Mg Phosphate Binders

Ion Chromatography Study of Ca/Mg Phosphate Binders

Hospitalizations and Red Blood Cell (RBC) Transfusions in Patients with Dialysis-Dependent-CKD (DD-CKD) on Auryxia® Compared with Other Phosphate Binders

Hospitalizations and Red Blood Cell (RBC) Transfusions in Patients with Dialysis-Dependent-CKD (DD-CKD) on Auryxia® Compared with Other Phosphate Binders

Sociodemographic Characteristics of Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide and Other Phosphate Binders

Sociodemographic Characteristics of Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide and Other Phosphate Binders