scholarly journals P1404A PHASE 2 OPEN-LABEL, SINGLE-ARM, FIRST JAPANESE STUDY OF TENAPANOR, A NOVEL PHOSPHATE ABSORPTION INHIBITOR, FOCUSING ON PILL BURDEN DECREASE IN PATIENTS WITH HYPERPHOSPHATEMIA UNDERGOING HEMODIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tadao Akizawa ◽  
Hironori Kanda ◽  
Masayuki Takanuma ◽  
Jun Kinoshita ◽  
Masafumi Fukagawa
Keyword(s):  
Primary Endpoint ◽  
Serum Phosphorus ◽  
Phosphate Binders ◽  
Pill Burden ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Open Label ◽  
Serious Adverse Events ◽  
Phosphate Absorption ◽  
Phosphorus Control

Abstract Background and Aims Phosphate binders (PB) are usually prescribed to dialysis patients with hyperphosphatemia. Several studies have reported that higher PB pill burden may reduce adherence and lead to insufficient phosphorus control. Tenapanor is an investigational, minimally absorbed, orally administered, non-binder, small-molecule that inhibits the sodium/hydrogen exchanger isoform 3 (NHE3) in development for the control of serum phosphorus. A previous Ph3 study sponsored by Ardelyx, Inc. (NCT02675998) showed a significant phosphorus decrease compared to the placebo in patients with hyperphosphatemia undergoing hemodialysis (HD) in the US. Tenapanor was expected to reduce PB pill burden since it is administered as one small pill, taken twice a day. This was the first study in Japanese HD patients, which aimed to confirm whether tenapanor reduces the pill burden of PB. Method This was a multicenter, open-label, single-arm Ph2 study. The study consists of a screening period, a 3-week observation period, and a 26-week treatment period. Patients whose serum phosphorus level was ≥ 3.5 and ≤ 7.0 mg/dL, taking at least two PB pills three times a day were enrolled. The patients started to receive 30 mg of tenapanor twice daily. The tenapanor dose could be reduced in a step-wise manner (60, 40, 20 and 10 mg/day) at the investigator’s discretion, based on GI tolerability. PB treatment was continued according to individual regimens, however, the dose could be adjusted appropriately to maintain serum phosphorus level within ±0.5 mg/dL from the baseline. The primary endpoint was an achievement of at least a 30% decrease in the mean of the total number of PB and tenapanor pills compared to the number of PB pills at baseline. The proportion of patients who achieved at least a 30 % decrease were tested using binomial test with a threshold level of 20% and a one-sided significance level of 0.025. The analysis was conducted using the data as of Dec25, 2019. Results The primary endpoint was met. Of 67 enrolled patients at the timing of analysis, 48 patients (71.6%, [95% CI: 59.3% - 82.0%], p<0.001) achieved a 30% decrease in the total number of PB and tenapanor pills, and of those, 35 patients (52.2%, [95% CI: 39.7% - 64.6%]) achieved a 50% decrease and 18 patients (26.9%) no longer required the use of any PB at week 26. Mean phosphorus levels were maintained during the study from 5.2 mg/dL at the baseline to 4.7 mg/dL at week 26. The most frequent adverse event was diarrhea (76.1%), which was mostly mild to moderate. Only four patients discontinued the study due to diarrhea. Serious adverse events were reported in five patients, only two of which were related to tenapanor (diarrhea and acute myocardial infarction). Conclusion Tenapanor was able to provide phosphorus control with significantly fewer pills compared to PB. AE profile was similar to previous US studies. This result suggests that tenapanor, a non-binder, phosphate absorption inhibitor that provides a novel approach to the management of hyperphosphatemia, could potentially improve drug adherence by reducing PB pill burden while maintaining effective phosphorus control.

P0927THE IMPACT OF NUTRITIONAL EDUCATION ON PHOSPHORUS CONTROL IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kariem Mohamed Salem ◽  
Mohammed Kamal Nassar ◽  
Doaa Hamed El-Sabakhawi ◽  
Ousama Elshahat ◽  
Malak Nabil Amin ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Intervention Group ◽  
Hemodialysis Patients ◽  
Serum Phosphorus ◽  
Phosphate Binders ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Nutritional Education ◽  
Teaching Aids ◽  
Significant Difference

Abstract Background and Aims Hyperphosphatemia is frequently encountered in hemodialysis patients and is an important risk factor of cardiovascular diseases. It is usually difficult to be managed by phosphate binders and hemodialysis. This study was carried out to assess the effect of nutritional education (NE) on the control of serum phosphorus level in hemodialysis patients. Method An open label, single center randomized controlled trial was conducted in the nephrology department, New Mansoura General Hospital, Egypt. One hundred hemodialysis patients were randomized into two groups; intervention Group (IG) (n=50) subjected to NE program for 3 months and Control group (CG) (n=50) received the usual care. Nutritional education was applied for the intervention group, by a trained renal dietitian, in the form of educational sessions, booklets, procures, audio visual teaching aids and patient-tailored counselling. Nutritional evaluation was done for all patients using dietary history, 24 hour diet recall sheet and malnutrition inflammation score (MIS) in addition to assessment of anthropometrics measurements and routine laboratory tests before randomization and at the end of the study. Results Three months after randomization, body mass index, waist circumference and midarm muscle circumference (MAMC) were significantly lower among IG versus the CG (p=0.04, 0.04 and 0.004 respectively). MIS score was significantly lower among the IG compared to the CG (p=0.02). Regarding laboratory tests, serum phosphorus level and calcium X phosphorus product were significantly lower among IG compared to the CG at the end of the study (p<0.001 and =0.04 respectively) with a percent change of serum phosphorus of -13.8 ± 21.41 after NE. The percentage of patients with hyperphosphatemia (> 5.5 mg/dl) were significantly lower in the IG at the end of study (p=0.04). Other laboratory tests including serum albumin, hemoglobin level, iron status and urea reduction ratio did not show any significant difference between both groups. Conclusion NE applied to dialysis patients added to the control of hyperphosphaemia without exposing the patients to the risk of malnutrition, resulting from injudicious dietary restrictions.

scholarly journals Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia

2021 ◽  
pp. 1-11
Author(s):  
Takashi Shigematsu ◽  
Yotaro Une ◽  
Kazuaki Ikejiri ◽  
Hironori Kanda ◽  
Masafumi Fukagawa ◽  
...  
Keyword(s):  
Placebo Group ◽  
Hemodialysis Patients ◽  
Serum Phosphorus ◽  
Phosphate Binders ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
The Mean ◽  
Phosphorus Levels

<b><i>Introduction:</i></b> Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. <b><i>Methods:</i></b> This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. <b><i>Results:</i></b> In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; <i>p</i> &#x3c; 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. <b><i>Discussion/Conclusion:</i></b> Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.

FC 077LONG-TERM SAFETY OF TENAPANOR FOR THE CONTROL OF SERUM PHOSPHORUS IN PATIENTS WITH CKD ON DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Daniel Weiner ◽  
Steven Fishbane ◽  
Robert Lynn ◽  
Yang Yang ◽  
David Rosenbaum
Keyword(s):  
Adverse Events ◽  
Treatment Period ◽  
Serum Phosphorus ◽  
Withdrawal Period ◽  
Dialysis Patients ◽  
Open Label ◽  
Serious Adverse Events ◽  
Phosphate Absorption ◽  
Paracellular Absorption ◽  
Extension Period

Abstract Background and Aims Tenapanor, a first-in-class, phosphate absorption inhibitor blocks the paracellular absorption of phosphate in the GI tract by local inhibition of the sodium-hydrogen exchanger (NHE3). It therefore provides a novel, non-binder approach for managing hyperphosphatemia. Tenapanor is dosed as one small pill twice daily. In three pivotal trials, tenapanor met its primary phosphorus-lowering outcome. This report evaluates long-term safety data from the longest of these trials. Method This 52-week study consisted of a 26-week, open-label, randomized treatment period with a 12-week placebo-controlled randomized withdrawal period, followed by a 14-week open label safety extension period. Maintenance dialysis patients with serum phosphorus ≥ 6.0 mg/dL and a 1.5 mg/dL increase in serum phosphorus following phosphate binder washout were randomized 3:1 to receive tenapanor 30 mg twice daily or sevelamer carbonate, dosed per package insert. At end of the randomized treatment period all patients in the tenapanor arm were re-randomized 1:1 to either tenapanor or placebo for the randomized withdrawal period followed by tenapanor for the safety extension period. Sevelamer was used as a safety control for comparisons of serious adverse events/hospitalizations to tenapanor. Results Tenapanor was generally well tolerated, with diarrhea the only adverse event reported by &gt;5% of patients during the randomized treatment period. Diarrhea was typically mild-to-moderate in severity, transient, and occurred more commonly during the randomized treatment period than the randomized withdrawal or safety extension periods. Rates of serious adverse events leading to hospitalization were higher in patients treated with sevelamer than tenapanor (35.8% vs 24.6%). The highest reported percentages of serious adverse events were infections and infestations (16.1% vs 9.3%) cardiac disorders (8.0% vs 5.7%), respiratory, thoracic and mediastinal disorders (8.8% vs 5.5%), and metabolism and nutritional disorders (7.3% vs 3.6%) for sevelamer and tenapanor, respectively. Adverse events leading to death were higher in patients treated with sevelamer than tenapanor (3.6% vs 2.9%). Conclusion Among maintenance dialysis patients with hyperphosphatemia, tenapanor, a novel, non-binder, phosphate absorption inhibitor that blocks paracellular absorption of phosphorus with a one tablet twice daily dose, has an acceptable safety profile, and, if approved, may offer a new approach to the treatment of hyperphosphatemia.

Serum phosphorus level is related to degree of clinical response to up-titration of heart failure pharmacotherapy

2014 ◽  
Vol 177 (1) ◽  
pp. 248-254 ◽  
Author(s):  
Piotr Rozentryt ◽  
Jolanta Nowak ◽  
Jacek Niedziela ◽  
Bartosz Hudzik ◽  
Wolfram Doehner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Response ◽  
Serum Phosphorus ◽  
Phosphorus Level ◽  
Serum Phosphorus Level

scholarly journals Serum 25-hydroxyvitamin D level is negatively associated with serum phosphorus level among stage 3a-5 chronic kidney disease patients

Nefrología ◽  
2018 ◽  
Vol 38 (5) ◽  
pp. 514-519
Author(s):  
Ahmed Fayed ◽  
Mahmoud M. El Nokeety ◽  
Ahmed A. Heikal ◽  
Khaled Marzouk ◽  
Hany Hammad ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Phosphorus ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Negatively Associated ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

scholarly journals Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients

2020 ◽  
Author(s):  
Xiaobo Xue ◽  
Jing Ma ◽  
Yuxia Zhao ◽  
Aibin Zhao ◽  
Xiaohong Liu ◽  
...  
Keyword(s):  
Virus Disease ◽  
Common Type ◽  
Serum Phosphorus ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Absolute Value ◽  
Corona Virus ◽  
Significant Difference ◽  
Critical Patients ◽  
Phosphorus Levels

AbstractObjectiveRetrospectively analyze the clinical data of Corona Virus Disease 2019 (COVID-19) patients and explore the value of serum phosphorus level in evaluating the severity and prognosis of the disease.MethodsCOVID-19 patients transferred from the first emergency ward of Taiyuan fourth people’s Hospital from February 8 to March 3, 2020 were enrolled. The information of general conditions, clinical manifestations, laboratory indexes, nucleic acid detection and treatment were collected. The changes of blood phosphorus level and absolute value of lymphocytes in ordinary and severe/critical patients were recorded and compared.ResultsA total of 32 patients with COVID-19 were collected, including 12 cases of common type and 20 cases of severe/critical type. Before treatment, the serum phosphorus levels of the two groups were significantly lower than the normal level, and the serum phosphorus levels of the severe/critical patients were lower than those of the common type patients (t = 2.767, P < 0.010). After treatment, the serum phosphorus levels of the two groups reached normal, and there was no significant difference between the two groups (t = 0.231, P >0.819). The level of lymphocytes in severe/critical patients was lower than that in normal patients (t = 4.636, P < 0.001) before treatment. After treatment, the absolute value of lymphocytes in the two groups reached normal, and there was no significant difference between the two groups (t=1.208,P=0.237). There was a positive correlation between lymphocytes and serum phosphorus, and the correlation coefficient was 0.479.Conclusionhypophosphatemia is related to the severity of COVID-19, and strengthening the monitoring of serum phosphorus level of COVID-19’s severe/critical patients and correcting hypophosphatemia in time are of significance to improve the prognosis.

scholarly journals Tumor-induced osteomalacia with the culprit lesion located in the palm: a case report

2019 ◽  
Vol 47 (5) ◽  
pp. 2240-2247
Author(s):  
Yanying Qian ◽  
Zhijuan Dai ◽  
Cong Zhu ◽  
Luya Ruan ◽  
Saroj Thapa ◽  
...  
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Serum Phosphorus ◽  
Postoperative Phase ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Mineral Density ◽  
Metacarpal Bones ◽  
The Right ◽  
Fgf 23

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. We herein report a rare case of TIO in a 58-year-old Chinese man who presented with a large lump in the right palm. Clinical, biochemical, and radiological assessments were performed. Laboratory examination showed severe hypophosphatemia, phosphaturia, an elevated serum alkaline phosphatase level, and an elevated serum fibroblast growth factor 23 (FGF-23) level. Dual-energy X-ray absorptiometry showed low bone mineral density. Magnetic resonance imaging revealed an irregular mass located in the right palm and abnormal findings in several metacarpal bones. During the operation, the surgeons found that the tumor had penetrated the surrounding muscles. The tumor had unique characteristics of local tissue invasion. The patient’s symptoms fully resolved and his serum phosphorus level normalized, although his serum FGF-23 level remained slightly high in the postoperative phase. Our findings suggest that in some patients with TIO, the serum phosphorus level might return to the normal range despite a relatively high postoperative serum FGF-23 level. These patients should be kept under close observation and regularly surveyed for any evidence of a residual tumor.

scholarly journals Strong Correlation of Renal Function with Choroidal Thickness in Patients with Type 2 Diabetes: Retrospective Cross-Sectional Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2171
Author(s):  
Min Gyu Choi ◽  
Jee Taek Kim
Keyword(s):  
Renal Function ◽  
Kidney Function ◽  
Cystatin C ◽  
Choroidal Thickness ◽  
Serum Phosphorus ◽  
Control Group ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Cross Sectional ◽  
Treatment Naïve

The purpose of this study was to analyze the correlation between renal function and subfoveal choroidal thickness (SFChT) in treatment-naïve proliferative diabetic retinopathy (PDR) patients. This study included 85 eyes of 52 treatment-naïve PDR patients who underwent kidney function testing and urinalysis and 42 eyes of 33 age-matched controls. Treatment-naïve eyes with PDR were categorized into pachychoroid and leptochoroid groups based on the SFChT of the control group. Kidney function profiles were compared between pachychoroid and leptochoroid groups; the relationship between kidney function profile and SFChT was evaluated using regression analysis. Compared with the pachychoroid group, the leptochoroid group had significantly higher serum creatinine (p = 0.026), cystatin C (p = 0.004), and phosphorus (p < 0.001) levels and a lower estimated glomerular filtration rate (eGFR) (p < 0.001). Multivariate linear regression analyses showed that SFChT was positively correlated with eGFR (Cystatin C) (p = 0.007) and negatively correlated with serum phosphorus (p = 0.001). SFChT of patients with eGFR < 30 mL/min/1.73 m2 and serum phosphorus level ≥4.0 mg/dL was less than that of patients with higher eGFR and lower serum phosphorus level. The choroidal thickness of treatment-naïve PDR patients is closely affected by renal function. Kidney function test should be considered if SFChT of patients with treatment-naïve PDR is reduced.

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