scholarly journals Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease

2017 ◽  
Vol 45 (5) ◽  
pp. 380-388 ◽  
Author(s):  
Edouard R. Martin ◽  
Mark T. Smith ◽  
Bradley J. Maroni ◽  
Qing C. Zuraw ◽  
Emil M. deGoma
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Binding Capacity ◽  
Small Sample Size ◽  
Small Sample ◽  
Dependent Manner ◽  
Short Treatment ◽  
Double Blind ◽  
Ckd Stage ◽  
Factor C

Background: Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD. Methods: A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to CKD stage 3 or 4. Eligible subjects were evenly randomized to 5 groups: 240, 370, 500, or 630 mg of once-daily oral vadadustat or placebo for 6 weeks. All subjects received low-dose supplemental oral iron (50 mg daily). The primary endpoint was the mean absolute change in hemoglobin (Hb) from baseline to the end of treatment. Secondary endpoints included iron indices, safety, and tolerability. Results: Ninety-three subjects were randomized. Compared with placebo, vadadustat significantly increased Hb after 6 weeks in a dose-dependent manner (analysis of variance; p < 0.0001). Vadadustat increased the total iron-binding capacity and decreased concentrations of ferritin and hepcidin. The proportion of subjects with at least 1 treatment-emergent adverse event was similar between vadadustat- and placebo-treated groups. No significant changes in blood pressure, vascular endothelial growth factor, C-reactive protein, or total cholesterol were observed. Limitations of this study included its small sample size and short treatment duration. Conclusions: Vadadustat increased Hb levels and improved biomarkers of iron mobilization and utilization in patients with anemia secondary to stage 3 or 4 CKD. Global multicenter, randomized phase 3 trials are ongoing in non-dialysis-dependent and dialysis-dependent patients.

scholarly journals A Placebo-Controlled, Randomized Trial of Enarodustat in Patients with Chronic Kidney Disease Followed by Long-Term Trial

2019 ◽  
Vol 49 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Tadao Akizawa ◽  
Masaomi Nangaku ◽  
Takuhiro Yamaguchi ◽  
Masanobu Arai ◽  
Ryosuke Koretomo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Binding Capacity ◽  
Hypoxia Inducible Factor ◽  
Target Range ◽  
Adaptive Responses ◽  
Double Blind ◽  
Hypoxic Conditions ◽  
Period 2 ◽  
Term Trial

Background: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis. Methods: Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10.0–12.0 g/dL in reference to a dose adjustment algorithm (Period 2). Results: In the correction group, Hb level increase rate per week increased in a dose-response manner. The proportion of subjects in the conversion group who maintained Hb levels within ± 1.0 g/dL of baseline did not differ between each enarodustat arm and placebo arm during Period 1. Over 70% of subjects in both groups maintained Hb levels within the target range at the end of treatment in Period 2. The mean prescribed doses were 3.58 and 3.74 mg/day in the correction group and the conversion group, respectively. Enarodustat was associated with decreases in hepcidin and ferritin and increased total iron-binding capacity and was generally well tolerated. Conclusions: Enarodustat corrects and maintains Hb levels in anemic patients with CKD not on dialysis.

scholarly journals TO001EFFECTS OF THE BET-INHIBITOR APABETALONE ON CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ACUTE CORONARY SYNDROME, ACCORDING TO PRESENCE OR ABSENCE OF CHRONIC KIDNEY DISEASE. A BETONMACE TRIAL REPORT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kam Kalantar-Zadeh ◽  
Kausik K Ray ◽  
Stephen J Nicholls ◽  
Henry N Ginsburg ◽  
Kevin A Buhr ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
High Risk ◽  
Kidney Disease ◽  
Myocardial Infarct ◽  
Double Blind ◽  
Coronary Syndrome ◽  
Ckd Stage

Abstract Background and Aims Patients with type 2 diabetes (T2D) and acute coronary syndrome (ACS) are at high risk for recurrent cardiovascular (CV) events, particularly in the presence of chronic kidney disease (CKD). Apabetalone (APB) is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Its cardiovascular efficacy and safety were evaluated in a phase 3 trial, BETonMACE. Method BETonMACE was a randomized, double-blind, comparison of effects of ABP or placebo (PBO) on major adverse CV events (MACE) defined as CV-death, non-fatal myocardial infarct or stroke, in 2425 pts with T2D and recent ACS. Here we report MACE plus CHF hospitalization in subjects with or without CKD Stage 3. Results Baseline characteristics: median age 62 years, 25.6% female, 87.6% white, 90% high intensity statin use, mean LDL-C 70.3 and HDL-C 33.3 mg/dl, median HbA1c 7.3%, and 11% with CKD Stage 3. Overall in the trial, MACE plus CHF hospitalization occurred in 139 (11.5%) patients with ABP and 173 (14.3%) with PBO (HR 0.78, 95% CI 0.63-0.98). In the subgroup with CKD, MACE plus CHF hospitalization occurred in 16 (12.9%) on APB and 41 (25%) on PBO (HR 0.48, 95% CI 0.26-0.89). In the subgroup without CKD, MACE plus CHF hospitalization occurred in 123 (11.3%) and 132 (12.7%) with APB or PBO, respectively (HR 0.89, 95% CI 0.70-1. Conclusion Patients with T2D, ACS, and Stage 3 CKD have a very high risk of subsequent MACE plus CHF hospitalization. The BET protein inhibitor ABP may reduce this risk.

scholarly journals Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease

2020 ◽  
Author(s):  
Aaron Broadwell ◽  
Arkadi Chines ◽  
Peter R Ebeling ◽  
Edward Franek ◽  
Shuang Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mineral Density ◽  
Pivotal Phase ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Ckd Stage ◽  
Moderate Chronic Kidney Disease ◽  
To Receive

Abstract Context The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. Objective This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. Participants and Methods Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than –2.5 to greater than –4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. Results Most participants (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. Conclusion The safety and efficacy of denosumab did not differ among participants with mild to moderate CKD.

scholarly journals Urine and serum midkine levels in an Australian chronic kidney disease clinic population: an observational study

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e014615 ◽  
Author(s):  
Victoria K Campbell ◽  
Chris M Anstey ◽  
Ryan P Gately ◽  
Drew C Comeau ◽  
Carolyn J Clark ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Demographic Data ◽  
Renin Angiotensin System ◽  
Outpatient Setting ◽  
Small Sample ◽  
Published Data ◽  
Ckd Stage ◽  
Stage 1 ◽  
Serum And Urine

Background and objectivesThe cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication.MethodsIn this observational, single-centre study, demographic data were collected, and serum and urine assayed from 197 patients with CKD and 19 healthy volunteers in an outpatient setting.ResultsThe median serum and urine MK level in volunteers was 754 pg/mL (IQR: 554–1025) and 239 pg/mL (IQR: 154–568), respectively. Compared with serum MK in stage 1 CKD (660 pg/mL, IQR: 417–893), serum MK increased in stage 3 (1878 pg/mL, IQR: 1188–2756; p<0.001), 4 (2768 pg/mL, IQR: 2065–4735; p<0.001) and 5 (4816 pg/mL, IQ: 37477807; p<0.001). Urine MK levels increased from stage 1 CKD (343 pg/mL, IQR: 147–437) to stage 3 (1007 pg/mL, IQR: 465–2766; p=0.07), 4 (2961 pg/mL, IQR: 1368–5686; p=0.005) and 5 (6722 pg/mL, IQR: 3796–10 060; p=0.001). Fractional MK excretion (FeMK) increased from stage 1 CKD (0.159, IQR: 0.145–0.299) to stage 3 (1.024, IQR: 0.451–1.886, p=0.047), 4 (3.39, IQR: 2.10–5.82, p=0.004) and 5 (11.95, IQR: 5.36–24.41, p<0.001). When adjusted for estimated glomerular filtration rate, neither serum nor urine MK correlated with primary CKD diagnosis or CKD progression (small sample). There was a positive correlation between protein:creatinine ratio and FeMK (p=0.003). Angiotensin blockade (adjusted for proteinuria) was associated with lower urine MK (p=0.018) and FeMK (p=0.025).ConclusionMK levels sequentially rise with CKD stage beyond stage 2, and our data support existing animal evidence for an MK/renin angiotensin-system/proteinuria relationship. To what extent this is related to renal clearance versus pathology, or the consequences of chronically elevated MK levels requires further exploration.

Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease

2016 ◽  
Vol 44 (4) ◽  
pp. 316-325 ◽  
Author(s):  
Stuart M. Sprague ◽  
Paul W. Crawford ◽  
Joel Z. Melnick ◽  
Stephen A. Strugnell ◽  
Shaukat Ali ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Extended Release ◽  
Vitamin D Insufficiency ◽  
Double Blind ◽  
Hydroxyvitamin D ◽  
Ckd Stage ◽  
25 Hydroxyvitamin D

Background/Aims: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Methods: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. Results: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Conclusion: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

scholarly journals Assessment of Risk Factors for Cardiovascular Complications in Patients with Chronic Kidney Disease (CKD) Stage III-V before Dialysis

2014 ◽  
Vol 9 (1) ◽  
pp. 25-32
Author(s):  
MK Khan ◽  
HU Rashid ◽  
S Yesmine ◽  
IH Mahmoo ◽  
SMA Habib ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Small Sample ◽  
Stage Iii ◽  
Ckd Stage

Background: Chronic Kidney Disease is a major public health and clinical problem throughout the world including Bangladesh. The prevalence of cardiovascular complications is much higher in patients with CKD regardless of stages than normal population. Considering this view, a cross sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, with an aim to assessing the cardiovascular complications & associated risk factors among the patients with chronic kidney disease (CKD) stage III-V before dialysis. Methods: A total of 109 patients were selected consecutively who had a diagnosis of CKD and an estimated GFR of less than 60 ml/min/1.73m2 of stages III to V and who had not received any form of renal replacement therapy, during a period of June 2006 to July 2007. Results: The study included 63 males and 46 females with age ranging from 18 to 65 years having a mean age 45.5±12.2 years. Left ventricular failure, left ventricular hypertrophy (by ECG and echocardiography), cardiomegally by X-ray were identified as significant cardiovascular complications among the patients of CKD stage V (p<0.05). However , logistic regression analysis revealed that hypertension and CKD stages appeared to be the important predictors of cardiovascular complications p<0.05). Data analysis found that hypertension, smoking and anemia appeared to be important risk factors for cardiovascular complications in CKD patients (p<0.05) by bi-variate analysis. Conclusion: Though the study findings did not generalize the CKD patients in Bangladesh due to small sample size, however, heart failure and left ventricular hypertrophy significantly appeared to be the main cardiovascular complications in CKD stage V compared to other two stages (stage III and IV)(p<0.05). Anemia, hypertension were identified as important risk factors (p<0.05). DOI: http://dx.doi.org/10.3329/uhj.v9i1.19508 University Heart Journal Vol. 9, No. 1, January 2013; 25-32

scholarly journals New Possibilities in Quantitative Assessment of Albuminuria in Patients with Atrial Fibrillation and Chronic Kidney Disease

2021 ◽  
Vol 17 (3) ◽  
pp. 423-428
Author(s):  
A. A. Sokolova ◽  
A. I. Skripka ◽  
I. I. Ivanov ◽  
V. V. Kogay ◽  
A. I. Listratov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Randomized Clinical Trials ◽  
Small Sample Size ◽  
Small Sample ◽  
Median Score ◽  
Ckd Progression ◽  
Patients With Diabetes

Aim. To evaluate the relationship between albumin to creatinine ratio (ACR) in a single and 24-hours urine spots and chronic kidney disease (CKD) progression pace in patients with atrial fibrillation, CKD and diabetes mellitus.Material and methods. 60 patients with atrial fibrillation (AF) and CKD were enrolled, study duration was 15 months. The patients were divided into two groups depending on the presence of DM. Total number of ACR tests was 170, dynamics of CKD progression was estimated with CKD-EPI formula for first visit and 15th month’s follow-up.Results. The median score of CHA2DS2VASс scale was 4 [3;5]. The risk of hemorrhagic complications in both groups was low (median score 1 [1;1]. There is a strong statistically significant correlation between ACR in a single and 24-hours urine spots (p<0.001). No significant changes in kidney function within 15 months were found (GFR 53 [46;59] ml/min/1.73 m2 vs 50.5 [45.63] ml/min/1.73 m2 for patients with diabetes mellitus [DM] [p=0.94] and GFR 52.5 [46.58] ml/min/1.73 m2 vs 50 [44.58] ml/min/1.73 m2 for patients without DM [p=0.711]). When comparing the renal function of patients with and without DM after 15 months statistically significant differences were also not found (p = 0.510).Conclusion. In respect that assessment of single sample ACR is much more practical and reliable, this method might replace traditional 24-hours urine assessment in future. However, due to the small sample size and the presence of wide discrepancies in individual cases, which can be associated with preanalytical errors in urine collection, large randomized clinical trials are needed to confirm the obtained data.

MO815BEYOND SURVIVAL: COMPARISON OF HEMODIALYSIS AND CONSERVATIVE MANAGEMENT IN ELDERLY AND FRAIL STAGE 5 CHRONIC KIDNEY DISEASE PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Inês Sala ◽  
João Oliveira ◽  
Joana Freitas ◽  
Joana Tavares ◽  
Josefina Santos Lascasas ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Survival Rate ◽  
Kidney Disease ◽  
Conservative Management ◽  
Small Sample Size ◽  
Small Sample ◽  
Clinical Frailty Scale ◽  
One Year

Abstract Background and Aims With the geriatric population increasing, the patients reaching stage 5 chronic kidney disease (CKD) are older, frailer and have multiple comorbidities. Technological advances in renal replacement therapy (RRT) and easier access to dialysis resulted in an expansion on geriatric dialysis population. Conservative management (CM) is an option that should be considered in this population, where is crucial to balance the survival and quality of life. Beside mortality, with this study we aim to evaluated patient-outcomes (hospitalization, falls and functional capacity) in older and frailer stage 5 CKD patients receiving hemodialysis (HD) and in CM. Method We conducted a single center retrospective study in older (≥ 75years), frailer (Clinical Frailty Scale – CFS ≥ 5) and with multiple comorbidities (modified Charlson comorbidity index – mCCI ≥ 5 and) stage 5 CKD patients, admitted in our Nephrology department between January 1, 2014 to December 31, 2020. The eGFR was calculated through Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) at the time of decision or at the time of starting HD. The comorbidities were stratified using the mCCI and frailty was assessed with CFS at the time of decision in CM group (CMG) and at the start of HD (HDG). We evaluated hospitalizations, falls, CFS one-year later and survival in each group. Survival analysis was performed using the Kaplan–Meier method and was calculated at the beginning of RRT or eGFR ≤ 15ml/min/1.73m2 in CMG. Differences between the two groups were tested with Mann-Whitney U method. Results A total of 76 patients with indication to start RRT were included: 61.8% (n=47) initiated HD and 38.2% (n=29) were in CM. The reasons for CM decision were deterioration of clinical condition (n=11), expected survival less than 6 months (n=8), patient option (n=5) and cognitive impairment (n=5). Clinical characteristics are presented in Table 1. The CMG was older [median, IQR: 88 (85.5-90.5) vs 80 (77.0 – 83.0), p &lt; 0.001] and had a lower BMI [23.44 (21.08 - 25.08) vs 26.23 (23.26 – 29.20), p=0.006]. Both groups did not differ significantly in terms of sex, CKD etiology, comorbidity or frailty. A total of 66 patients died at the end of the study [CMG 100% (n= 29) vs 78.7% HDG (n=37)]. The overall survival has higher on the HDG compared to the CMG with a median survival rate of 503 days (Fig 1). One-year survival rate was 53.5% in HDG vs 24% CMG (p &lt;0.001). The median (IQR) of number of hospitalizations per patient was greater in the HDG [4 (1.5-6.5) vs 3 (0.5-5.5) CMG]. In HDG 17% patients had at least one fall vs 3.4% in CMG. In both groups there was a general deterioration associated to a higher CFS at one-year follow up (p=0.003 HD group vs p=0.015 CMG). Conclusion In our study, hemodialysis was associated to improved survival in older and frailer stage 5 CKD patients compared to CM. However, this group had more hospitalizations, falls and poor functional status. These outcomes have a crucial impact on quality of life in this population and should be consider at the time of treatment decision. One of the limitations of our study was small sample size in both groups. In the future, we consider that is important to perform multicenter studies focused on patients-outcomes. We also think that it’s important to understand the patient and family perspective in terms of quality of life and symptom burden associated to each treatment option.

scholarly journals Chronic Kidney Disease and Dietary Supplementation: Effects on Inflammation and Oxidative Stress

2021 ◽  
Vol 8 (11) ◽  
pp. 277
Author(s):  
Elisa Martello ◽  
Francesca Perondi ◽  
Natascia Bruni ◽  
Donal Bisanzio ◽  
Giorgia Meineri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Dietary Supplement ◽  
Dietary Supplementation ◽  
Good Control ◽  
Acid Base Balance ◽  
Double Blind ◽  
Ckd Stage ◽  
And Oxidative Stress

Chronic kidney disease (CKD) causes an irreversible loss of kidney functioning in dogs. This double-blind case-control study evaluates the efficacy of a dietary supplement, which contains calcium carbonate, calcium lactate-gluconate, chitosan, sodium bicarbonate, Lactobacillus acidophilus D2/CSL, Olea europaea L. extract, and fructooligosaccharides, in dogs in advanced CKD stage. Thirty dogs were enrolled in the study; half were administered the new dietary supplementation for 90 days, while the others were used as controls. Hematologic, biochemical, and urinalysis were performed. This novel dietary supplement mainly reported a good control of uremia, phosphate, acid-base balance, blood pressure, inflammation, and oxidative stress in dogs with advanced stages of CKD.

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