Sliced Jelly Whole Swallowing Reduces Deglutition Risk: A Novel Feeding Method for Patients with Dysphagia.

Texture modification in the form of gels or jellies is used for patients with dysphagia. For over 20 years, our group has been using gelatin jellies, a type of gel, as a starting diet for patients with dysphagia. Gelatin jellies are served in a small-sliced form and swallowed whole. In sliced jelly whole swallowing (SJWS), sliced gelatin jelly (SGJ) passes through the pharynx in one lump without collapsing. This study aimed to examine the usefulness of SJWS. We analyzed the images of videofluoroscopic swallowing studies performed using the normalized residue ratio scale (NRRSv: vallecula, NRRSp: pyriform sinus), the penetration-aspiration scale (PAS), and pharyngeal transit time (PTT) in 50 patients with dysphagia and compared the results in a prospective study. SJWS had significantly less residue in both NRRSv and NRRSp than in moderately thickened liquid swallowing. No significant differences in PAS scores were found between SGJ and moderately thickened liquid. Additionally, no significant differences in PTT scores were noted between the two. This study demonstrated the usefulness of SJWS in improving swallowing safety in patients with dysphagia. Further studies are needed to evaluate the reproducibility of the test, the comparison of SGJ with other thickened liquids, and the safety of SJWS for different diseases.

Bisphosphonate FYB-931 Prevents High Phosphate-Induced Vascular Calcification in Rat Aortic Rings by Altering the Dynamics of the Transformation of Calciprotein Particles.

Patients with chronic kidney disease develop vascular calcification, owing to impaired calcium and phosphate metabolism. The prevention of vascular calcification is important to improve the prognosis of such patients. In this study, we investigated whether treatment with FYB-931, a novel bisphosphonate compound, prevents vascular calcification in rat aortic rings cultured in high-phosphate medium for 9 days, assessed by measurement of the calcium content and the degree of calcium deposition, visualized using von Kossa staining. The effect on the transformation of calciprotein particles (CPPs) from primary to secondary CPPs was assessed using a fluorescent probe-based flow cytometric assay. FYB-931 dose-dependently prevented high phosphate-induced aortic calcification, but failed to rapidly cause the regression of high phosphate-induced vascular calcification once it had developed. Furthermore, the treatment dose-dependently inhibited the high phosphate-induced transformation from primary to secondary CPPs. In addition, the treatment with FYB-931 prevented the transformation from primary to secondary CPPs in vitamin D3-treated rats as a model of ectopic calcification, consistent with the results from rat aortic rings. In conclusion, treatment with FYB-931 prevents high phosphate-induced rat aortic vascular calcification by altering the dynamics of CPP transformation. This finding suggests that inhibition of the transformation from primary to secondary CPPs is an important target for the prevention of vascular calcification in patients with chronic kidney disease.

Cricopharyngeal muscle origin transection for oropharyngeal dysphagia, a novel surgical technique.

BACKGROUND: Cricopharyngeal myotomy improves pharyngeal dysphagia by resecting the cricopharyngeal muscle. METHODS: Our procedure, cricopharyngeal muscle origin transection (CPM-OT) is performed through a midline skin incision at the cricoid cartilage level under local anesthesia. CONCLUSIONS: Sixteen patients demonstrated preservation of vocal fold movement without laryngeal nerve injury immediately after CPM-OT in the awake state during aspiration prevention surgery using the glottic closure technique. Postoperative videofluoroscopic examination of swallowing revealed the cricopharyngeal bar was absent and pharyngeal passage of the bolus and Food Intake LEVEL Scale was improved in all patients. CPM-OT is a feasible and less invasive treatment option.

A Safe Way to Administer Drugs Through a Nutrition Tube-The Simple Suspension Method.

The simple suspension method (SSM), developed by Kurata in 1997, is a way to suspend tablets and capsules in warm water for decay and suspension prior to their administration. This method is safe and has various advantages such as the avoidance of tube clogging and the loss of the drug. This study aimed to investigate whether a higher percentage of commonly used drugs could pass through nutrition tubes effectively using SSM, relative to that using the conventional crushing method. A tablet or capsule was inserted into a 20 mL syringe with warm water (at 55 °C). After 10 min, it was shaken in the syringe. The suspension liquid was injected into tubes of the following sizes: 8 Fr, 10 Fr, 12 Fr, 14 Fr, 16 Fr, and 18 Fr. A total of 3686 tablets and 432 capsules that are frequently used in Japan were tested. Using SSM, 3377 (91.6%) tablets and 359 (83.1%) capsules disintegrated within 10 min and passed through the tube without clogging it in the tube passage test. With the conventional crushing method, 2117 tablets (57.4%) and 272 capsules (63.0%) could be crushed. SSM reduced the risk of tube clogging and drug loss with more drugs than that with the conventional crushing method. The number of drugs indicated for administration by SSM is greater than that indicated by the conventional crushing method. Further studies are needed to consider its utility compared to conventional methods for dysphagia patients in clinical settings.

Cough-Inducing Method Using a Tartaric Acid Nebulizer for Patients with Silent Aspiration.

The tartaric acid nebulizer is a well-known cough test to evaluate cough function. This study aimed to evaluate the effectiveness of a cough-inducing method using tartaric acid (CiTA). Patients with dysphagia examined by videofluoroscopic examination of swallowing (VF) at a single institution from May 2017 to August 2017 were included in this retrospective observational study. Although undergoing VF, patients who had aspirated without reflexively coughing or who had coughed insufficiently, were instructed to cough voluntarily. Patients who could not cough voluntarily or had expectorated insufficiently underwent the CiTA method. The rate of cough induction and the effectiveness of expectoration using the CiTA method were evaluated. One hundred fifty-four patients (mean age 69.2 ± 16.8 years) were evaluated. Eighty-seven patients aspirated during VF. Of those patients, 15 were able to expectorate via the cough reflex, 18 were able to expectorate with a voluntary cough, and 12 required suctioning for removal of aspirated material. The remaining 42 patients underwent the CiTA method. Thirty-eight patients (90.4%) could reflexively cough, and 30 (71.4%) could expectorate the aspirated material. This novel method, CiTA, was effective for cough induction in patients with dysphagia, especially for those with silent aspiration.

Food appearance affects reward-related brain activity in healthy adults: a functional magnetic resonance imaging study.

A good appearance of food increases appetite. A new food product called iEat® resembles the appearance and softness of familiar foods. Previous studies have reported that iEat® foods increase appetite. However, the neuronal substrates underlying the increase in appetite following the observation of iEat® foods remain unknown. In the present study, the brain activity of 20 healthy adults during the visual presentation of iEat® and pureed foods and non-food objects was examined using functional magnetic resonance imaging. Compared with pureed foods and non-food objects, iEat® foods showed significantly greater activation in regions of the brain reward system, such as the amygdala, ventral striatum and orbital frontal cortex. In addition, individual differences in the activity of the left amygdala were positively correlated with subjective appetite ratings. These results suggest that the good appearance of foods, such as iEat® foods, may be useful for stimulating the appetite of patients with poor appetite.

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

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.

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan.

BACKGROUND: Etelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan. METHODS: This PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician's discretion. RESULTS: Of 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60-240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled. CONCLUSION: This was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

Effect of Bridge Position Swallow on Esophageal Motility in Healthy Individuals Using High-Resolution Manometry.

Recently, there has been clinical interest in the effect of different body positions on esophageal motility. This study aimed to identify the effect of three different body positions on esophageal motility using high-resolution manometry. Thirteen healthy adults swallowed 5 mL of water in the upright, supine, and bridge positions. For the bridge position, each subject raised their waist against gravity, placed a cushion under their back, and bent their knees. The proximal contractile integral (PCI) and distal contractile integral (DCI), integrated relaxation pressure (IRP), distal latency (DL), peristaltic breaks (PBs), intrabolus pressure (IBP), and expiratory and inspiratory esophagoesophageal junction (EGJ) pressure were measured. In the bridge position, PCI, DCI, IRP, and expiratory and inspiratory EGJ pressure were significantly higher than those in the upright position (bridge PCI vs. upright PCI [p = 0.001], bridge DCI vs. upright DCI [p < 0.001], bridge IRP vs. upright IRP [p = 0.018], bridge EGJ pressure vs. upright EGJ pressure [expiratory: p = 0.001] [inspiratory: p < 0.001]). PBs were significantly shorter and DL was significantly longer in the bridge position compared to upright (bridge PBs vs. upright PBs [p = 0.001], bridge DL vs. upright DL [p = 0.001]). IBP was significantly higher in the bridge position compared to supine (bridge IBP vs. supine IBP [p = 0.01]). These results demonstrated changes in esophageal motility according to changes in position while swallowing, where esophageal contractions became stronger against gravity. Further study is required to examine the effectiveness of swallowing in the bridge position.

Relationship Between Tongue Pressure and Pharyngeal Function Assessed Using High-Resolution Manometry in Older Dysphagia Patients with Sarcopenia: A Pilot Study.

Tongue pressure is often used to evaluate swallowing muscle strength in dysphagia patients with sarcopenia. However, the amount of tongue pressure that reflects pharyngeal swallowing function is unclear. The aims of this descriptive study were (1) to assess the association between tongue pressure and swallowing function using high-resolution manometry (HRM), (2) to evaluate whether manometric parameters were related to maximum tongue pressure (MTP) and other sarcopenia-related factors, and (3) to evaluate the manometric characteristics of pharyngeal swallowing in sarcopenic dysphagia. Sixteen patients with dysphagia (13 men; mean age 85.0 ± 6.6) who were diagnosed with sarcopenia and sixteen healthy subjects (10 men; mean age 33.6 ± 7.2) were included. Evaluation of HRM parameters including velopharyngeal contractile integral (VPCI), mesohypopharyngeal contractile integral (MHPCI), upper esophageal sphincter (UES) relaxation duration, and UES nadir pressure was performed. HRM parameters of patients were compared with MTP, sarcopenia factors, and manometric parameters of healthy subjects. The VPCI showed no statistically significant differences between patient and healthy groups. In the patient group, the MHPCI was significantly lower (126.1 ± 76.6 vs 193.2 ± 34.1 mmHg cm s; p = 0.003), UES nadir pressure was significantly higher (10.5 ± 27.5 vs - 11.2 ± 6.7 mmHg; p < 0.001), and UES relaxation duration (318.0 ± 152.4 vs 520.6 ± 60.0 ms; p = 0.007) was significantly shorter than those in the healthy group. HRM parameters were not significantly correlated with MTP and sarcopenia factors. Older dysphagia patients with sarcopenia had weaker pharyngeal contractility and UES dysfunction. Manometric evaluation of pharyngeal function may not be significantly associated with MTP and sarcopenia-related factors. Further study is needed to clinically apply tongue pressure for evaluating sarcopenic dysphagia.

Diagnosis and Treatment of Sarcopenic Dysphagia: A Scoping Review.

BACKGROUND: Sarcopenic dysphagia is a swallowing disorder due to sarcopenia involving the whole-body skeletal muscles and swallowing muscles. This scoping review aimed to explore the currently known information on the diagnosis and treatment of sarcopenic dysphagia and to clarify the types of research required to develop the field. METHODS: We searched the PubMed, MEDLINE, CINAHL, and Cochrane databases from their inception to October 2020, using the search terms "(sarcopenia or sarcopenic or myopenia or dynapenia) and (dysphagia or swallowing or deglutition) and (diagnosis or treatment)". Articles reporting diagnosis method and treatment of sarcopenic dysphagia were included. RESULTS: Twenty-one and eight articles reported on the diagnostic and treatment method, respectively. A diagnostic algorithm for sarcopenic dysphagia was most frequently used (n = 10). Other diagnostic methods included consensus diagnostic criteria for sarcopenic dysphagia (n = 4), sarcopenia and dysphagia without other causes of dysphagia (n = 4), and both sarcopenia and dysphagia (n = 3). The medical treatments for patients with sarcopenic dysphagia were described in single-patient case reports (n = 8) only. There were six articles reporting on a combination of rehabilitation and nutritional support. These reports showed the importance of interdisciplinary rehabilitation nutrition for improving patients' nutritional status and sarcopenia. CONCLUSIONS: A reliable and validated diagnostic algorithm was the most widely used diagnostic method for sarcopenic dysphagia. Only case reports have been published for the medical treatment of patients with sarcopenic dysphagia. Interdisciplinary rehabilitation nutrition may be useful for treating patients with sarcopenic dysphagia.

Influence of dialysate Ca concentrations on the therapeutic effects of etelcalcetide with concomitant drugs in patients with secondary hyperparathyroidism.

AIM: Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs. METHODS: We performed post hoc analyses of a 52-week, open-label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate-resistant acid phosphatase 5b (TRACP-5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses. RESULTS: There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60-240 pg/mL, 8.4-10.0 mg/dL and 3.5-6.0 mg/dL, respectively) across the three groups. TRACP-5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group. CONCLUSION: The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment.

Novel bisphosphonate compound FYB-931 preferentially inhibits aortic calcification in vitamin D3-treated rats.

In patients with chronic kidney disease (CKD) or those undergoing hemodialysis, pathological calcific deposition known as ectopic calcification occurs in soft tissue, resulting in a life-threatening disorder. A potent and effective inhibitor of ectopic calcification is eagerly expected. In the current study, the effects of FYB-931, a novel bisphosphonate compound synthesized for the prevention of ectopic calcification, were compared with those of etidronate using both in vitro and in vivo models. In vitro, FYB-931 inhibited calcification of human aortic smooth muscle cells induced by high phosphate medium in a concentration-dependent manner, and the effect was slightly more potent than that of etidronate. In vivo, rats were administered with three subcutaneous injections of vitamin D3 to induce vascular calcification, and were given FYB-931 (1.5, 5, or 10 mg/kg) or etidronate (9, 30, or 60 mg/kg) orally once daily for 14 days. The increased aortic phosphorus content as an index of vascular calcification was inhibited by both FYB-931 and etidronate in a dose-dependent manner; however, FYB-931 was 10 times more potent than etidronate. FYB-931 inhibited serum tartrate-resistant acid phosphatase (TRACP) activity as a bone resorption marker 5.2 times more potently than etidronate. FYB-931, but not etidronate, significantly decreased serum phosphorus levels. The preferential inhibition of aortic calcification by FYB-931 suggested that possible additional effect including a decline in serum phosphorus may lead to an advantage in terms of its efficacy.

Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan.

Limited data are available on the safety and efficacy of anti-resorptive agents, particularly once-monthly bisphosphonates, for use in osteoporotic patients with chronic kidney disease (CKD). We conducted a post hoc analysis of data from a 12-month, randomized, double-blind, phase III study to evaluate the safety and efficacy of once-monthly risedronate (RIS-OM) 75 mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75 mg were stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 90, ≥ 60 to < 90, or ≥ 30 to < 60 mL/min/1.73 m2). Safety endpoints were incidence of adverse events (AEs) and percent change from baseline in eGFR, serum creatinine, calcium, and phosphorus. Efficacy endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs). In 420 patients included (age 67.7 ± 6.7 years, women 98.8%), the incidence of all AEs, gastrointestinal disorders, acute phase reaction, non-vertebral fractures, and renal and urinary disorders was not significantly different among subgroups. Interaction between subgroups and time was significant for eGFR (p = 0.010) and serum creatinine (p = 0.001) but considered to be regression to the mean and clinically insignificant. BMD significantly increased while BTMs significantly decreased from baseline with a similar degree of change among the subgroups. In conclusion, RIS-OM 75 mg showed consistent safety and efficacy in suppressing bone turnover and increasing BMD in Japanese primary osteoporosis patients with mild-to-moderate CKD. These results should, however, be interpreted with caution because the number of patients with moderate CKD was limited.

Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients.

BACKGROUND: This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis. METHODS: In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events. RESULTS: Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased). CONCLUSION: Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.

Association of Circulatory Iron Deficiency With an Enlarged Heart in Patients With End-Stage Kidney Disease.

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.

[The prevention and treatment of vascular calcification.]

We had called the various bone disorder in chronic kidney disease(CKD)as a "ROD:renal osteodystrophy" until last decade. However the concept of ROD have changed into the chronic kidney disease-mineral and bone disease(CKD-MBD)within this decade. This concept is containing systemic disorder affected mortality. Vascular calcification is an independent risk factor for the development of cardiovascular disease and mortality. The best strategy to prevent and treat vascular calcification would consist of the CKD-MBD management. It is expected that the treatment of preventing directly vascular calcification to appear by finding the detailed mechanism in the future.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression.

BACKGROUND: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). METHODS: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. RESULTS: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. CONCLUSION: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies.

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.

Long-term effects of etelcalcetide as intravenous calcimimetic therapy in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a serious major complication in hemodialysis patients with chronic kidney disease. Long-term maintenance of serum phosphate, calcium, and parathyroid hormone (PTH) levels in appropriate ranges in these patients is a major challenge. We investigated the efficacy and safety of long-term treatment with etelcalcetide, a novel intravenous calcimimetic, in Japanese SHPT patients on long-term hemodialysis. METHODS: This study was a multicenter open-label study. A total of 191 hemodialysis patients with serum intact PTH (iPTH) > 240 pg/mL were enrolled. Etelcalcetide was administered thrice weekly for 52 weeks, with an initial dose of 5 mg and flexibility to adjust the dose between 2.5 and 15 mg and to adjust the dosing of concomitant medications for SHPT. The efficacy endpoint was the proportion of patients with serum iPTH decreased to the target range (60-240 pg/mL). RESULTS: Serum iPTH levels decreased immediately after etelcalcetide was started. At the end of the study, 87.5% (95% confidence interval 81.4-92.2; 140/160 patients) of patients achieved target serum iPTH levels, with control of serum calcium and phosphate levels. Adverse events, mostly mild to moderate, were reported by 96.8% of patients and led to study discontinuation in 7.4% of patients. Nausea, vomiting, and symptomatic hypocalcemia were found in 4.7, 9.5, and 1.1%, with 0.5, 1.1, and 1.1% considered treatment-related. CONCLUSIONS: Etelcalcetide effectively maintained serum iPTH, calcium, and phosphate levels in appropriate ranges with concomitant medications for SHPT for 52 weeks in Japanese hemodialysis patients, and was safe and well tolerated. REGISTRATION NUMBER: JapicCTI-142665.