Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.
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SUBMITTER: Kanai H
PROVIDER: S-EPMC9290017 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSecondary hyperparathyroidism (SHPT) is a serious and common complication in patients receiving peritoneal dialysis (PD). Cinacalcet is currently the recommended therapy for SHPT; however, gastrointestinal (GI)-related symptoms can result in low adherence and high discontinuation rates. Evocalcet is a novel calcimimetic agent that has non-inferior efficacy while providing a more tolerable safety profile.MethodsThis was a multicenter, intra-subject dose-adjustment treatment study evaluating the efficacy and safety of 1-8 mg evocalcet orally administered once daily for 32 weeks for the treatment of SHPT in PD patients. Patients then entered a 20-week extension period (dose range 1-12 mg). The primary endpoint was the proportion of patients who achieved a mean intact parathyroid hormone (iPTH) level of 60-240 pg/mL during the evaluation period (weeks 30-32). Secondary efficacy endpoints included the proportion of patients achieving ≥ 30% decrease in iPTH levels.ResultsA total of 39 Japanese PD patients with SHPT received evocalcet. The target mean iPTH level of 60-240 pg/mL was achieved by 71.8% (28/39) of patients during the evaluation period and 83.3% (20/24) of patients at week 52. The proportion of patients who achieved ≥ 30% decrease in iPTH levels from baseline was 74.4% (29/39) during the evaluation period and 87.5% (21/24) at week 52. Adverse drug reactions occurred in 46.2% (18/39) of patients, with most being of mild-to-moderate severity including GI-related events.ConclusionThis study shows the long-term efficacy and safety of evocalcet when orally administered to PD patients with SHPT once daily.Clinical trial registrationClinicalTrials.gov: NCT02549417, https://clinicaltrials.gov/ct2/show/NCT02549417 ; JAPIC: JapicCTI-153016, http://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-153016 .
| S-EPMC6586709 | biostudies-literature
Project description:BackgroundWe report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance.MethodsWe performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively.Results108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline.ConclusionsWe demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.
| S-EPMC5648742 | biostudies-literature
Project description:IntroductionEndoscopic procedures can provoke peritonitis in patients receiving peritoneal dialysis (PD). The aim of this study was to assess the development of peritonitis after endoscopic procedures in PD patients.MethodsWe retrospectively reviewed the data from PD patients who underwent endoscopies in 3 tertiary hospitals between 2008 and 2018. The patients were grouped into nonprophylactic, prophylactic, and prior antibiotic therapy groups. The incidence of peritonitis within 7 days of endoscopy was assessed. We also examined the factors associated with peritonitis.ResultsThere were 1,316 endoscopies performed in 570 PD patients. The peritonitis rate after endoscopy was 3.0%. Specifically, the peritonitis rate was 1.8% for esophagogastroduodenoscopies, 4.2% for the colonoscopy group, and 5.3% for the sigmoidoscopy group. The prior antibiotic therapy group showed a significantly higher risk of peritonitis (odds ratio = 4.6; 95% confidence interval: 2.2-9.6; P < 0.01). Prophylactic antibiotics were not associated with reducing peritonitis. Therapeutic colonoscopies such as polypectomy were associated with an increased risk of developing peritonitis (odds ratio = 6.5; 95% confidence interval: 1.6-25.9). However, biopsies were not associated with an increased risk of peritonitis.DiscussionProphylactic antibiotics did not reduce the risk of peritonitis after endoscopy in PD patients. Therapeutic colonoscopies such as polypectomy and prior antibiotic therapy before endoscopy were associated with an increased risk of peritonitis.
| S-EPMC8345910 | biostudies-literature
Project description:ImportanceDaprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.ObjectiveTo evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.Design, setting, and participantsThis prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.InterventionsRandomized 1:1 to daprodustat or darbepoetin alfa.Main outcomes and measuresThe primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.ResultsA total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.Conclusions and relevanceThis randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.Trial registrationClinicalTrials.gov Identifier: NCT03029208.
| S-EPMC8981070 | biostudies-literature
Project description:Background and objectivesDaprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates genes related to iron metabolism. The efficacy (noninferiority) and safety of daprodustat compared with standard therapy (darbepoetin alfa) was evaluated.Design, setting, participants, & measurementsThis was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants' treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10-60 μg once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40-52 in the intent-to-treat population.ResultsOf 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40-52 were maintained within the target range in both groups (10.9 g/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g/dl; 95% CI, -0.1 to 0.2 g/dl) was greater than the noninferiority criterion of -1.0 g/dl. For most participants, hemoglobin was maintained within the target range (10.0-12.0 g/dl) during weeks 40-52 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (-37%; 95% CI, -49 to -23) than with darbepoetin alfa (-20%; 95% CI, -36 to -1), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa.ConclusionsOral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40-52 in Japanese patients receiving hemodialysis switched from ESAs.Clinical trial registry name and registration number201754, Clinicaltrials.gov, NCT02969655.
| S-EPMC7409739 | biostudies-literature
Project description:BACKGROUND:It is known that patients on hemodialysis (HD) are prone to developing zinc deficiency due to removal of zinc by HD, inadequate dietary intake, and reduced gastrointestinal zinc absorption. However, the prevalence of zinc deficiency in patients on peritoneal dialysis (PD) has not been well established. METHODS:Serum zinc levels were compared between 47 patients on PD and 47 patients on HD matched for age, sex, and duration of dialysis. A serum zinc level < 60 ?g/dL was defined as clinical zinc deficiency and a level of 60-80 ?g/dL as subclinical zinc deficiency. The prevalence of zinc deficiency and associated clinical factors were determined in both groups. RESULTS:Clinical zinc deficiency was found in 59.6% of the PD group and 70.2% of the HD group (p = 0.391). Subclinical zinc deficiency was found in 40.4% of the PD group and 29.8% of the HD group. Age, body mass index, and serum albumin level were identified as independent predictors of zinc deficiency in the PD group by multivariate analysis. CONCLUSIONS:A higher prevalence of clinical and subclinical zinc deficiency was found in patients on PD. The rates were comparable between patients on PD and those on HD after adjustment for confounding factors.
| S-EPMC7146559 | biostudies-literature
Project description:BackgroundIrisin is a recently discovered myokine thought to be involved in multiple metabolism abnormalities in most dialysis patients. However, the myokine has not been thoroughly studied in peritoneal dialysis. This study aimed to evaluate serum irisin levels and establish their relation to dialysis adequacy, insulin resistance, and bone metabolism status in patients on peritoneal dialysis.MethodsA total of 59 nondiabetic prevalent peritoneal dialysis patients and 52 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentration was assessed by enzyme-linked immunosorbent assay. The correlations between serum irisin and dialysis adequacy, clinical, and metabolic variables were investigated.ResultsSerum irisin levels were lower in nondiabetic peritoneal dialysis patients (17.02ng/ml) compared with healthy controls (22.17ng/ml, P<0.001). Multivariate regression analysis revealed that fasting glucose levels were correlated inversely with serum irisin levels in peritoneal dialysis patients. Serum irisin levels were associated with neither insulin resistance nor bone metabolism in our patients. Serum irisin levels were positively associated with peritoneal Kt/Vurea (β = 4.933, 95% confidence interval [CI] = 0.536-9.331, P = 0.029) and peritoneal CCr (β = 0.259, 95% CI = 0.053-0.465, P = 0.015) among peritoneal dialysis patients.ConclusionsThe study demonstrated that non-diabetic peritoneal dialysis patients have lower serum irisin levels, and the levels were correlated with peritoneal dialysis adequacy, indicating adequate dialysis may improve irisin secretion. Additional studies are needed to provide a confirmation.
| S-EPMC5406024 | biostudies-literature
Project description:BackgroundResults concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up.MethodsThis retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality.ResultsA total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years.ConclusionsPeritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.
| S-EPMC5460447 | biostudies-literature
Project description:BackgroundHigher serum β2-microglobulin (B2M) concentrations are associated with higher mortality in the general population, non-dialyzed chronic kidney disease patients and patients receiving hemodialysis (HD). However, this relationship among patients on peritoneal dialysis (PD) has not been validated.MethodsWe collected baseline data for 3,011 prevalent PD patients from a nationwide dialysis registry in Japan at the end of 2010. Clinical outcomes for 9 years were then evaluated using the registry at the end of 2011 to 2019. All-cause and cardiovascular (CV) mortality was assessed using Cox regression analysis and competing-risks regression analysis, respectively. We used multiple imputation to deal with missing covariate data.ResultsDuring a median follow-up of 87 months, 2,054 patients transferred to combined therapy with PD and HD or HD directly. A total of 3,011 patients, 1,235 (41.0%) died, including 437 patients (14.5%) from CV causes. Among them, 612 patients died after transfer to other dialysis modalities. Univariate analyses revealed no significant association between serum B2M and mortality, whereas higher serum B2M was independently associated with both all-cause and CV mortalities in adjusted models. However, the significant association between serum B2M and CV mortality disappeared in analysis treating serum B2M as a categorical variable. The effect of serum B2M on all-cause mortality was significantly higher among patients with higher urinary volume and a significant interaction was evident.ConclusionsUsing a large-scale registry, we found that serum B2M contributes tenuously but significantly to worse outcome and residual kidney function significantly affects this relationship. On the contrary, serum B2M per se had no predictive value for patient outcome in prevalent PD patients.
| S-EPMC9009671 | biostudies-literature
Project description:Objectives: Whether automated peritoneal dialysis (APD) is a feasible strategy in perioperative period of uremic patients undergoing nonabdominal surgery remains unclear. This study was conducted to research the perioperative management and the best choice of dialysis modalities for peritoneal dialysis patients. Materials and methods: A retrospective analysis was made on the clinical data of 58 ESRD patients who had received peritoneal dialysis for more than three months were treated with APD during perioperative period from July 2015 to March 2018 in the Second Affiliated Hospital of Soochow University. The differences of clinical parameters, such as urine volume, ultrafiltration volume, hemoglobin, renal function and electrolytes were collected and analyzed before and after APD. Results: The vital signs of 58 patients were stable after APD treatment, and there were no significant differences in 24-hour urine volume, hemoglobin and electrolytes (calcium, phosphorus, potassium, sodium) before and after surgery (P>0.05). Compared with those before treatment, the amount of ultrafiltration increased significantly (P<0.05), creatinine, urea nitrogen and parathyroid hormone decreased significantly (P<0.05), while albumin decreased (P<0.05). Conclusion: Application of APD for peritoneal dialysis patients undergoing nonabdominal surgery during the perioperative period is safe and effective.
| S-EPMC6538830 | biostudies-other