scholarly journals Dulaglutide in Diabetes and Chronic Kidney Disease: AWARD-7 Exploratory Analysis of Clinical Outcomes

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0005852020
Author(s):  
Katherine R. Tuttle ◽  
Brian Rayner ◽  
Mark C. Lakshmanan ◽  
Anita Y.M. Kwan ◽  
Manige Konig ◽  
...  

Background: In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe chronic kidney disease (CKD), dulaglutide (DU) treatment slowed decline in estimated glomerular filtration rate (eGFR) compared to insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and blood pressure. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Methods: Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to DU 0.75 mg or 1.5 mg weekly or IG daily as basal therapy, with titrated insulin lispro, for one year. The time to occurrence of the composite outcome of ≥40% eGFR decline, end-stage kidney disease (ESKD), or death due to kidney disease was compared using a Cox proportional hazards model. Results: Patients treated with DU 1.5 mg weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5.2% versus 10.8%; hazard ratio 0.45, 95% confidence interval 0.20-0.97, P=0.042). Most events occurred in the subset with macroalbuminuria, where risk of the composite outcome was substantially lower for DU 1.5 mg versus IG (7.1% versus 22.2%; hazard ratio 0.25, 95% confidence interval 0.10-0.68, P=0.006). No deaths occurred. Conclusions: Treatment with DU 1.5 mg weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared to IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.

Author(s):  
Min-Hua Lin ◽  
She-Yu Chiu ◽  
Pei-Hsuan Chang ◽  
Yu-Liang Lai ◽  
Pau-Chung Chen ◽  
...  

Background: Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease.


2015 ◽  
Vol 22 (8) ◽  
pp. 1086-1093 ◽  
Author(s):  
Saeed Akhtar ◽  
Raed Alroughani ◽  
Samar F Ahmed ◽  
Jasem Y Al-Hashel

Background: The frequency of paediatric-onset multiple sclerosis (POMS) and the precise risk of secondary progression of disease are largely unknown in the Middle East. This cross-sectional cohort study assessed the risk and examined prognostic factors for time to onset of secondary progressive multiple sclerosis (SPMS) in a cohort of POMS patients. Methods: The Kuwait National MS Registry database was used to identify a cohort of POMS cases (diagnosed at age <18 years) from 1994 to 2013. Data were abstracted from patients’ records. A Cox proportional hazards model was used to evaluate the prognostic significance of the variables considered. Results: Of 808 multiple sclerosis (MS) patients, 127 (15.7%) were POMS cases. The median age (years) at disease onset was 16.0 (range 6.5–17.9). Of 127 POMS cases, 20 (15.8%) developed SPMS. A multivariable Cox proportional hazards model showed that at MS onset, brainstem involvement (adjusted hazard ratio 5.71; 95% confidence interval 1.53–21.30; P=0.010), and POMS patient age at MS onset (adjusted hazard ratio 1.38; 95% confidence interval 1.01–1.88; P=0.042) were significantly associated with the increased risk of a secondary progressive disease course. Conclusions: This study showed that POMS patients with brainstem/cerebellar presentation and a relatively higher age at MS onset had disposition for SPMS and warrant an aggressive therapeutic approach.


2020 ◽  
Vol 45 (2) ◽  
pp. 339-349
Author(s):  
Hanako Nakajima ◽  
Yoshitaka Hashimoto ◽  
Takuro Okamura ◽  
Akihiro Obora ◽  
Takao Kojima ◽  
...  

Background: The duration of sleep might be a risk factor for chronic kidney disease (CKD). We investigated the relationship between sleep duration and incident CKD. Methods: In this retrospective cohort study of 7,752 men and 6,722 women, we divided the subjects into 4 groups according to sleep duration, i.e., those whose reported regular sleep duration was <6 h (the “<6 h group”), those whose sleep duration was >6 but <7 h (the “6 to <7 h group”), those with a sleep duration of 7 to <8 h (the “7 to <8 h group”), and those with ≥8 h sleep (the “≥8 h group”). CKD was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The HR of the 4 groups for incident CKD were calculated with a Cox proportional hazards model, with the 7 to <8 h group set as the reference. Results: Incident CKD was detected in 1,513 (19.5%) men and 688 (10.2%) women over the median follow-up period of 7.0 (3.3–11.9) years in the men and 6.7 (3.1–10.8) years in the women. There was no association between sleep duration and incident CKD in the women. In the men, the HR of incident CKD was 0.54 (95% CI 0.45–0.64, p < 0.001) in the <6 h group, 0.73 (95% CI 0.66–0.82, p < 0.001) in the 6 to <7 h group, and 0.93 (95% CI 0.78–1.11, p = 0.433) in the ≥8 h group. Conclusion: The risk of incident CKD is lowest in those who sleep <6 h. We revealed that the risk of incident CKD is lowest in those who sleep <6 h among apparently healthy men.


2021 ◽  
Vol 10 (2) ◽  
pp. 363
Author(s):  
Tae Ryom Oh ◽  
Su Hyun Song ◽  
Hong Sang Choi ◽  
Chang Seong Kim ◽  
Seung Hyeok Han ◽  
...  

Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. This study aimed to determine the effect of serum hemoglobin on the progression of IgA nephropathy. We retrospectively analyzed 4326 patients with biopsy-proven IgA nephropathy. We evaluated the effect of serum hemoglobin on IgA nephropathy progression using Kaplan–Meier survival analyses, the log-rank test, and the Cox proportional hazards model. The primary end-point was progression of IgA nephropathy, defined as dialysis initiation or kidney transplantation. Serum hemoglobin showed a nonlinear relationship with the progression of IgA nephropathy. The Cox proportional hazards model showed that the risk of progression of IgA nephropathy decreased 0.87 times for every 1.0 g/dL increase in serum hemoglobin. In subgroup analyses, reduced serum hemoglobin was an independent risk factor for IgA nephropathy progression only in women. There was no statistically significant interaction of serum hemoglobin between men and women (Pinteraction = 0.177). Results of Sensitivity analysis were robust and consistent. Serum hemoglobin at diagnosis was an independent predictor for IgA nephropathy progression.


2021 ◽  
Author(s):  
Daisuke Takada ◽  
Susumu Kunisawa ◽  
Akira Kikuno ◽  
Tomoko Iritani ◽  
Yuichi Imanaka

Background Several social determinants of health are associated with the progression of chronic kidney disease (CKD). We compared the risk of CKD progression among 18 occupational classifications using an annual health-checkup database. Methods We used the annual health checkup data and health insurance claims data of the Japan Health Insurance Association in Kyoto prefecture between April 2012 and March 2016. The primary outcome for survival analysis was defined as a more than 30% change in the estimated glomerular filtration rate (eGFR) from the first health checkup. We used the Cox proportional-hazards model for time-to-event analyses to estimate the hazard ratio, and 95% CIs for the primary outcome, adjusting for age, sex, eGFR, body mass index, blood pressure, blood sugar, dyslipidemia, uric acid, urinary protein, and existence of kidney diseases at first health checkup. Results We analyzed 239,506 employees, and 1,736 (0.7%) individuals whose eGFR had decreased by 30% or more; the mean follow-up period was 2.8 years (standard deviation: 1.2 years). When we compared the risk for manufacturing, five categories of industries (information and communications; transport and postal services; accommodations, eating and drinking services; living-related and personal services and amusement service; medical, health care and welfare) were associated with a decline in the risk of eGFR after adjusting for the confounding factors and/or mediators. Conclusions We provided evidence that the risk of CKD progression depends on occupation type. Further research is needed to confirm the mechanism and causal relationships involved.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jonathan Barratt ◽  
Nada Dimkovic ◽  
Evgeny Shutov ◽  
Wladyslaw Sulowicz ◽  
Ciro Esposito ◽  
...  

Abstract Background and Aims Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, induces a coordinated erythropoietic response by increasing endogenous erythropoietin levels and improving iron metabolism. This analysis was performed to examine the consistency of efficacy and cardiovascular safety results for roxadustat vs placebo or darbepoetin alfa (DA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD). Method Results from three phase 3, double-blind studies comparing roxadustat with placebo (ALPS, ANDES, OLYMPUS) with anaemia and stage 3-5 NDD CKD were pooled and assessed for consistency with results of an open-label study comparing roxadustat with DA (DOLOMITES) in predominantly European patients. The primary efficacy endpoint was haemoglobin (Hb) response, defined as (a) Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb &gt;8.0 g/dL or (b) Hb CFB by ≥2.0 g/dL in patients with Hb ≤8.0 g/dL irrespective of and without rescue therapy for placebo-controlled (assessed for superiority) and DA-controlled (assessed for non-inferiority) studies, respectively. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 using least squares mean difference (LSMD) without rescue therapy. The key safety endpoints of major adverse cardiovascular event (MACE, comprising death, myocardial infarction, and stroke) and MACE+ (MACE plus hospitalization with heart failure or unstable angina) were adjudicated in all studies. MACE and MACE+ for roxadustat vs placebo or DA were compared in the intention-to-treat sample using a Cox proportional hazards model. Results In total, 4886 patients were randomised in placebo-controlled (2386 roxadustat, 1884 placebo) and DA-controlled (323 roxadustat, 293 DA) studies. Baseline characteristics of patients treated with roxadustat vs placebo and roxadustat vs DA were similar: baseline Hb (placebo, 9.10 vs 9.10 g/dL; DA, 9.55 vs 9.55 g/dL) and iron repletion (placebo, 59.9% vs 59.8%; DA, 56.3% vs 51.9%). Roxadustat was superior to placebo for Hb response without rescue therapy (80.2% vs 8.7%; difference of proportion [DOP], 71.50%; 95% CI, 69.40-73.51) and noninferior to DA (89.5% vs 78.0%; DOP, 11.51%; 95% CI, 5.66-17.36). Mean Hb CFB (Weeks 28-36) achieved superiority in pooled analysis vs placebo (LS mean, 1.91 vs 0.14; LSMD, 1.77; 95% CI, 1.69-1.84; P&lt;0.0001) and noninferiority vs DA (LS mean, 1.85 vs 1.84; LSMD, 0.02; 95% CI, -0.13 to 0.16). Risk for MACE or MACE+ was similar for roxadustat vs placebo (MACE, 480 [20.1%] vs 350 [18.6%]; HR, 1.10; 95% CI, 0.96-1.27; MACE+, 578 [24.2%] vs 432 [22.9%]; HR, 1.07; 95% CI, 0.94-1.21) and vs DA (MACE, 38 [11.8%] vs 41 [14.0%]; HR, 0.81; 95% CI, 0.52-1.25; MACE+, 54 [16.7%] vs 43 [18.1%]; HR, 0.90; 95% CI, 0.61-1.32). Conclusion Roxadustat corrected Hb more effectively than placebo and comparably to DA in patients with anaemia and stage 3-5 NDD CKD. Cardiovascular safety was comparable between roxadustat and DA and placebo.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Katherine Tuttle ◽  
David Cherney ◽  
Samy Hadjadj ◽  
Thomas Idorn ◽  
Ofri Mosenzon ◽  
...  

Abstract Background and Aims The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a renal benefit with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo. The PIONEER 6 CVOT reported cardiovascular safety with oral semaglutide in a similar cohort using a similar trial design. In the present post hoc study, eGFR data from the SUSTAIN 6 and PIONEER 6 trials were pooled to evaluate the potential benefit of semaglutide (s.c. or oral) vs placebo on chronic kidney disease (CKD) outcomes. Method Data from 6,480 subjects from SUSTAIN 6 (N=3,297; median follow-up, 2.1 years; mean baseline eGFR, 76 mL/min/1.73 m2) and PIONEER 6 (N=3,183; median follow-up, 1.3 years; mean baseline eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 mg s.c. OW, 1.0 mg s.c. OW or 14 mg oral once daily) or placebo. We evaluated time to onset of persistent eGFR reduction (thresholds of ≥30%, ≥40%, ≥50% and ≥57% [57% corresponds to a doubling of serum creatinine]) from baseline in the overall pooled population and by baseline CKD subgroups (≥30–&lt;60 mL/min/1.73 m2, n=1,699; ≥60 mL/min/1.73 m2, n=4,762; data were missing for 19 subjects). Analyses were performed using a Cox proportional-hazards model with treatment group (semaglutide vs placebo) and CKD subgroup as fixed factors and the interaction between both stratified by trial. Results In the overall population, the hazard ratios (HRs) for time to onset of persistent eGFR reductions with semaglutide vs placebo were &lt;1.0, but did not achieve statistical significance. In subjects with baseline eGFR ≥30–&lt;60 mL/min/1.73 m2, HRs for semaglutide vs placebo were consistently lower compared with the overall population and, in this subgroup, semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs placebo (Figure; p=0.03). Numerically larger effects were seen with increasing eGFR reduction thresholds in this subgroup, with the exception of the 57% eGFR reduction threshold. No statistically different interactions between treatment and CKD subgroup were observed. Conclusion The findings of this post hoc analysis of pooled data from SUSTAIN 6 and PIONEER 6 on clinically relevant outcomes for CKD support a smaller magnitude of eGFR decline with semaglutide vs placebo, despite relatively short follow-up times. The small number of events at both the 50% and 57% thresholds, and the associated broad confidence intervals, limit the interpretability of the results. In line with previous findings, the data suggest a renal benefit of semaglutide vs placebo in subjects with established CKD. The FLOW trial (ClinicalTrials.gov Identifier: NCT03819153), which is dedicated to exploring CKD outcomes with semaglutide treatment, is ongoing to test this hypothesis in patients with CKD at baseline.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ting-Ting Chung ◽  
Kuang-Hui Yu ◽  
Chang-Fu Kuo ◽  
Shue-Fen Luo ◽  
Meng-Jiun Chiou ◽  
...  

Abstract Background This study investigates the association between exposure to urate-lowering drugs (ULDs) and progression and recovery from chronic kidney disease (CKD). Methods We identified 5860 incident gout patients at Chang Gung Memorial Hospital from 2012 to 2015. Propensity score (PS)-weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) for CKD progression and improvement. A separate analysis was conducted to assess the HR for CKD progression and CKD recovery among those with worsening CKD. Results The incidence of CKD progression among allopurinol, febuxostat and uricosuric agent users were 1.98, 1.88 and 1.64 per 1000 person-days. Compared with allopurinol users, the PS-weighted HR (95% confidence intervals [CIs]) was 1.77 (0.85–1.76) for febuxostat users and 1.37 (0.71–1.37) for uricosuric agent users for CKD progression and 1.43 (1.26–1.62) for febuxostat users and 1.00 (0.88–1.14) for uricosuric agent users for CKD improvement. Compared to allopurinol users, the HRs for CKD progression were 1.14 (0.80–1.66) for febuxostat users and 0.92 (0.67–1.31) for uricosuric agent users. Among 741 patients who had CKD progression, the incidence of CKD recovery was 1.33, 6.21 and 3.53 per 1000 person-days for allopurinol, febuxostat and uricosuric agent users. The HRs (95% CIs) for recovery in febuxostat and uricosuric agent users were 2.17 (1.40–3.47) and 1.80 (1.20–2.83) compared to allopurinol users. Conclusions CKD progression and recovery are common in gout patients using ULDs. Febuxostat and benzbromarone were associated with a similar risk of CKD progression with allopurinol, which has a poorer recovery compared with other ULDs.


2017 ◽  
Vol 7 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Kaoru Ando ◽  
Hiroyasu Sukekawa ◽  
Aoi Takahata ◽  
Yusuke Kobari ◽  
Hayato Tsuchiya ◽  
...  

Background: Left ventricular dysfunction as part of takotsubo syndrome is reversible, and the long-term prognosis appears favorable. However, life-threatening complications are not uncommon during the acute phase, and it remains unclear whether renal dysfunction is a factor in complications suffered by hospitalized patients with takotsubo syndrome. The present study was conducted to investigate the implications of renal dysfunction in this setting. Methods: Data from 61 consecutive patients (male, 21; female, 40) diagnosed with takotsubo syndrome at our hospital between years 2010 and 2016 were evaluated retrospectively. In-hospital complications by definition were all-cause deaths and severe pump failure (Killip class ≥III). Results: Overall, 30 patients (49%) developed renal dysfunction. In the 32 patients (52%) who suffered in-hospital complications (mortality, 10; severe pump failure, 22), estimated glomerular filtration rate (eGFR) was significantly lower by comparison (51.3±29.8 vs. 69.5±29.0; p=0.019). Low eGFR (<30 ml/min per 1.73m2) proved independently predictive of in-hospital complications (hazard ratio =2.84, 95% confidence interval: 1.20–6.69) in multivariate Cox hazard analysis, also showing a significant association with peak event rate of Kaplan–Meier curve (log-rank test, p=0.0073). Similarly, patients with chronic kidney disease were at significantly greater risk of in-hospital complications (hazard ratio=2.49, 95% confidence interval: 1.01–5.98), relative to non-compromised counterparts (eGFR >60 ml/min per 1.73m2). Conclusion: Renal dysfunction is a simple but useful means of predicting complications in hospitalized patients with takotsubo syndrome, especially those with chronic kidney disease.


Author(s):  
Jayeun Kim ◽  
Soong-Nang Jang ◽  
Jae-Young Lim

Background: Hip fracture is one of the significant public concerns in terms of long-term care in aging society. We aimed to investigate the risk for the incidence of hip fracture focusing on disability among older adults. Methods: This was a population-based retrospective cohort study, focusing on adults aged 65 years or over who were included in the Korean National Health Insurance Service–National Sample from 2004 to 2013 (N = 90,802). Hazard ratios with 95% confidence interval (CIs) were calculated using the Cox proportional hazards model according to disability adjusted for age, household income, underlying chronic diseases, and comorbidity index. Results: The incidence of hip fracture was higher among older adults with brain disability (6.3%) and mental disability (7.5%) than among those with other types of disability, as observed during the follow-up period. Risk of hip fracture was higher among those who were mildly to severely disabled (hazard ratio for severe disability = 1.59; 95% CI, 1.33–1.89; mild = 1.68; 95% CI, 1.49–1.88) compared to those who were not disabled. Older men with mental disabilities experienced an incidence of hip fracture that was almost five times higher (hazard ratio, 4.98; 95% CI, 1.86–13.31) versus those that were not disabled. Conclusions: Older adults with mental disabilities and brain disability should be closely monitored and assessed for risk of hip fracture.


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