Tenapanor: A novel therapeutic agent for dialysis patients with hyperphosphatemia.

Patients on dialysis often develop hyperphosphatemia, contributing to an increased risk of cardiovascular events and mortality. Currently, several types of phosphate binders (PBs) exist for the treatment of hyperphosphatemia, but they are sometimes associated with drug-specific side effects and high pill burden, making it difficult to control serum phosphorus appropriately. Tenapanor, which has a novel mechanism to reduce serum phosphorus via selective sodium/proton exchange transporter 3 inhibition, was approved for hyperphosphatemia in Japan in 2023.

Roxadustat Efficacy and Safety in Patients Receiving Peritoneal Dialysis: Pooled Analysis of Four Phase 3 Studies.

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). This analysis pooled data from four phase 3, multicenter, randomized, open-label, active-comparator studies (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES).

An 11-mer Synthetic Peptide Suppressing Aggregation of Aβ25-35 and Resolving Its Aggregated Form Improves Test Performance in an Aβ25-35-Induced Alzheimer's Mouse Model.

There is a high demand for the development of drugs against Alzheimer's disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), due to the increasing number of patients with AD. In our present study, we aimed to assess the aggregation inhibitory effect of various synthetic YS-peptides on Aβ25-35 to identify an applicable peptide for clinical use for AD treatment and prevention. Suppression and aggregate resolution activities of YS-peptides against Aβ25-35 were evaluated using a Thioflavin T assay and scanning electron microscopy (SEM).

Clinical Evaluation of Acute Exacerbation of Interstitial Lung Disease in a Single Tertiary Center: Perspectives before and after the Coronavirus Disease 2019 Pandemic.

Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes.

Long-Term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-Label 52-Week Study.

Introduction: Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).

Methods: Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.

Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Rationale & Objective: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend, and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival.

Physician and Patient Preferences for Treatment of Anemia Associated with Chronic Kidney Disease in Japan: A Survey Including Best-Worst Scaling.

Background: Several treatment options are available for anemia associated with chronic kidney disease (CKD); however, there remains a lack of awareness of physician and patient preferences regarding these treatments. We aimed to explore physicians' and patients' perceptions and preferences regarding the management of anemia of CKD in Japan.

Methods: A web-based survey, including best-worst scaling (BWS), was conducted with physicians who had treated ≥1 patient with anemia of CKD in the preceding year, and with patients with CKD who self-reported a clinical diagnosis of anemia of CKD or low hemoglobin levels.

SKGQA, a Peptide Derived from the ANA/BTG3 Protein, Cleaves Amyloid-β with Proteolytic Activity.

Despite the extensive research conducted on Alzheimer's disease (AD) over the years, no effective drug for AD treatment has been found. Therefore, the development of new drugs for the treatment of AD is of the utmost importance. We recently reported the proteolytic activities of JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMA), synthetic peptides of nine amino acids each, derived from the Box A region of Tob1 and ANA/BTG3 proteins, respectively.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

Introduction: The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear.

Methods: The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching.

Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.

Background: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA.

Methods: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials.

Introduction: Risk factors for thromboembolic events in patients with dialysis-dependent chronic kidney disease (CKD) receiving roxadustat are unknown. Iron deficiency has been reported as a risk factor for thrombosis in the general population.

Methods: Thromboembolic events with onset before and after week 12 in patients receiving roxadustat were evaluated in this pooled analysis of four global phase 3 trials, PYRENEES, SIERRAS, HIMALAYAS, and ROCKIES.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan.

Introduction: Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan.

Methods: Thromboembolic events with onset before and after week 12 were evaluated.

Impact of Cough Severity on the Diagnostic Yield of Endobronchial Ultrasonography Transbronchial Biopsy with Guide Sheath: A Retrospective Observational Study.

Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated.

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study.

Background: Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT).

Methods: A phase 2, multicentre, open-label, single-arm study was conducted.

Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia.

Introduction: Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels.

Effects of NRF2 polymorphisms on safety and efficacy of bardoxolone methyl: subanalysis of TSUBAKI study.

Background: In the TSUBAKI study, bardoxolone methyl significantly increased measured and estimated glomerular filtration rates (GFR) in patients with multiple forms of chronic kidney disease (CKD), including Japanese patients with type 2 diabetes and stage 3-4 CKD. Since bardoxolone methyl targets the nuclear factor erythroid 2-related factor 2 pathway, this exploratory analysis of the TSUBAKI study investigated the impact of the regulatory single nucleotide polymorphism, rs6721961, on the effects of bardoxolone methyl.

Methods: Japanese patients aged 20-79 years with type 2 diabetes and stage 3-4 CKD were randomized to bardoxolone methyl 5-15 mg/day (titrated as tolerated) or placebo for 16 weeks.

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.

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

Background: Tenapanor 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.

Methods: This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.

Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism: A Randomized Placebo-Controlled Trial.

Background: Secondary hyperparathyroidism is a major complication of patients undergoing hemodialysis (HD). Upacicalcet, a new injectable calcimimetic, acts on calcium-sensing receptors to suppress parathyroid hormone (PTH) secretion. We examined the efficacy and safety of upacicalcet in patients with secondary hyperparathyroidism receiving HD.

Iron Parameters in Patients Treated with Roxadustat for Anemia of Chronic Kidney Disease.

Roxadustat is a novel agent with a distinct mechanism of action compared to erythropoiesis-stimulating agents (ESAs) and a potentially different combination of effects on iron parameters. This narrative review describes the effects of roxadustat on iron parameters and on hemoglobin levels in the context of iron supplementation in patients with anemia of non-dialysis-dependent (NDD) or dialysis-dependent (DD) chronic kidney disease (CKD). Roxadustat use was associated with a greater reduction in serum ferritin levels than seen with ESAs and an increase in serum iron levels compared to a decrease with ESAs.

Efficacy of molnupiravir and sotrovimab in Japanese dialysis patients with COVID-19 in clinical practice during the Omicron (BA.1 and BA.2) pandemic.

Introduction: In the present study, the efficacy of sotrovimab and molnupiravir in dialysis patients with COVID-19 was investigated using a registry of COVID-19 in Japanese dialysis patients.

Methods: Dialysis patients with confirmed SARS-CoV-2 during the COVID-19 (Omicron BA.1 and BA.

Higher hemoglobin levels using darbepoetin alfa and kidney outcomes in advanced chronic kidney disease without diabetes: a prespecified secondary analysis of the PREDICT trial.

Background: In the primary analysis of the PREDICT trial, a higher hemoglobin target (11-13 g/dl) with darbepoetin alfa did not improve renal outcomes compared with a lower hemoglobin target (9-11 g/dl) in advanced chronic kidney disease (CKD) without diabetes. Prespecified secondary analyses were performed to further study the effects of targeting higher hemoglobin levels on renal outcomes.

Methods: Patients with an estimated glomerular filtration rate (eGFR) 8-20 ml/min/1.

Treatment satisfaction with molidustat in CKD-related anemia in non-dialysis patients: a post-hoc analysis of two clinical trials.

Background: Erythropoiesis-stimulating agents (ESAs) are the standard treatment for patients with renal anemia to increase hemoglobin (Hb) levels and reduce the need for blood transfusions. However, treatments targeting high Hb levels require high doses of ESAs administered intravenously, which is associated with an elevated risk of adverse cardiovascular events. Furthermore, there have been some problems such as hemoglobin variability and low achievement of target hemoglobin due to the shorter half-lives of ESAs.