Abstract 13331: Impact of Longer Hemodialysis Vintage With Higher Serum Phosphorus Level on Clinical Outcomes in Patients With Chronic Limb-threatening Ischemia

Background: Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI). Methods: The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Result: One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing. Conclusion: Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.

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Impact of Longer Hemodialysis Vintage with Higher Serum Phosphorus Level on Clinical Outcomes in Patients with Chronic Limb-Threatening Ischemia Presenting Tissue Loss after Endovascular Therapy

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat.60095 ◽

2021 ◽

Author(s):

Naoko Higashino ◽

Osamu Iida ◽

Yosuke Hata ◽

Mitsutoshi Asai ◽

Masaharu Masuda ◽

...

Keyword(s):

Clinical Outcomes ◽

Endovascular Therapy ◽

Serum Phosphorus ◽

Tissue Loss ◽

Phosphorus Level ◽

Serum Phosphorus Level

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

10.1101/2020.03.27.20040816 ◽

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.

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Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis

Journal of the American Society of Nephrology ◽

10.1681/asn.2020030290 ◽

2020 ◽

Vol 31 (11) ◽

pp. 2622-2630

Author(s):

Vishnu S. Potluri ◽

Deirdre Sawinski ◽

Vicky Tam ◽

Justine Shults ◽

Jordana B. Cohen ◽

...

Keyword(s):

Socioeconomic Status ◽

Food Environment ◽

Healthy Food ◽

Chronic Dialysis ◽

Serum Phosphorus ◽

Phosphorus Level ◽

Serum Phosphorus Level ◽

Neighborhood Food Environment ◽

Neighborhood Income ◽

Phosphorus Levels

BackgroundElevated blood phosphorus levels are common and associated with a greater risk of death for patients receiving chronic dialysis. Phosphorus-rich foods are prevalent in the American diet, and low-phosphorus foods, including fruits and vegetables, are often less available in areas with more poverty. The relative contributions of neighborhood food availability and socioeconomic status to phosphorus control in patients receiving dialysis are unknown.MethodsUsing longitudinal data from a national dialysis provider, we constructed hierarchical, linear mixed-effects models to evaluate the relationships between neighborhood food environment or socioeconomic status and serum phosphorus level among patients receiving incident dialysis.ResultsOur cohort included 258,510 patients receiving chronic hemodialysis in 2005–2013. Median age at dialysis initiation was 64 years, 45% were female, 32% were Black, and 15% were Hispanic. Within their residential zip code, patients had a median of 25 “less-healthy” food outlets (interquartile range, 11–40) available to them compared with a median of four “healthy” food outlets (interquartile range, 2–6). Living in a neighborhood with better availability of healthy food was not associated with a lower phosphorus level. Neighborhood income also was not associated with differences in phosphorus. Patient age, race, cause of ESKD, and mean monthly dialysis duration were most closely associated with phosphorus level.ConclusionsNeither neighborhood availability of healthy food options nor neighborhood income was associated with phosphorus levels in patients receiving chronic dialysis. Modifying factors, such as nutrition literacy, individual-level financial resources, and adherence to diet restrictions and medications, may be more powerful contributors than food environment to elevated phosphorus.

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Cinacalcet HCl Treatment in Patients with Chronic Kidney Disease Stage 3-4

Clinical Medicine Therapeutics ◽

10.4137/cmt.s3211 ◽

2009 ◽

Vol 1 ◽

pp. CMT.S3211 ◽

Cited By ~ 1

Author(s):

Yoshihiro Tominaga

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Chronic Kidney Disease Stage ◽

Serum Phosphorus ◽

Disease Stage ◽

Phosphorus Level ◽

Serum Phosphorus Level ◽

Ckd Stage ◽

Problematic Issue ◽

Phosphorus Levels

It has been clarified in patients with CKD stage 3-4, cinacalcet can reduce PTH levels without severe adverse events, however calcium levels significantly decrease and phosphorus levels increase. Increase of serum phosphorus level by cinacalcet in patients with CKD stage 3-4 is a problematic issue. Undesirable decreases in serum calcium and increases in serum phosphorus caused by cinacalcet require further investigation. For patients with CKD stage 3-4 who suffer from severely advanced 2HPT which cannot be controlled by the usual medical treatment or PTx, cinacalcet can be a useful medication for managing 2HPT.

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

American Journal of Nephrology ◽

10.1159/000516156 ◽

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

Introduction: 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. Methods: 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. Results: 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; p < 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. Discussion/Conclusion: 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.

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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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1404 ◽

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.

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