MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma

Abstract Background and Aims Patients with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular mortality and morbidity. Several clinical trials suggested that aldosterone antagonists would be a promising treatment option for patients undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for patients with CKD on dialysis have yet to be determined. This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 14 trials (12 parallel RCTs and two cross-over trials) involving a total of 1,375 participants. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 participants: RR 0.45, 95% CI 0.30 to 0.67; I=0%; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I=0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I=0%; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I=0%; moderate certainty of evidence), the elevated risk of hyperkalaemia (9 trials, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I=47%; low certainty of evidence) and increase in serum potassium (7 trials, 519 participants: MD 0.21, 95% CI -0.06 to 0.47; I2=84%) due to aldosterone antagonists was uncertain. Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (7 trials, 562 participants: SMD -0.33, 95% CI -0.72 to 0.05; I2=76%). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis. Two ongoing studies will provide better certainty of evidence in the future.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1467-1467
Author(s):  
Andrew Odegaard ◽  
David Jacobs ◽  
Lyn Steffen ◽  
Casey Rebholz ◽  
Katherine Tucker ◽  
...  

Abstract Objectives Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health. The underlying concern is the lack of data to support or refute this concept. To begin addressing this gap we examined the association between diet beverage intake and incident chronic kidney disease (CKD) in a population at high risk for CKD. Methods We pooled data from the Atherosclerosis Risk in Communities study (years 1987–2014), Cardiovascular Health Study (1989–2014), Jackson Heart Study (2000–2012), and Multi-Ethnic Study of Atherosclerosis (2000–2013) to conduct a prospective study of the association of diet beverage intake with the incidence of CKD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CKD and with valid dietary data (n = 3250). CKD was defined using serum creatinine to define estimated glomerular filtration (eGFR) via the CKD-EPI creatinine equation. Incident CKD was defined as (eGFR <60 ml/min/1.73 m2). We carried out a 2-step meta-analysis using individual level, cohort-specific regression analyses with identical adjustment for demographic, lifestyle, overall diet quality (Alternative Healthy Eating Index), energy intake, and clinical risk factors (baseline eGFR, total cholesterol, blood pressure, fasting glucose) to generate effect estimates that were pooled together using fixed and random effects meta-analysis. Results 1018 participants developed CKD during follow-up. There was a positive association between diet beverage intake and risk of CKD. Compared to individuals reporting no intake of diet beverages, those consuming >0 and <1 diet beverage per day had a pooled relative risk and 95% confidence interval (RR, 95% CI) of 1.03 (0.87–1.22) and those consuming ≥1 beverage per day had a pooled RR (95% CI) of 1.20 (1.02–1.41). Conclusions Diet beverage intake was associated with an increased risk of CKD in a diverse population with T2D. These results suggest the need to further examine the role of diet beverages in this high risk population. Funding Sources AHA.


2020 ◽  
Vol 45 (4) ◽  
pp. 565-575
Author(s):  
Qing-xiu Huang ◽  
Jian-bo Li ◽  
Naya Huang ◽  
Xiao-wen Huang ◽  
Yan-lin Li ◽  
...  

Introduction: Studies have shown inconsistent results regarding the association between osteoprotegerin (OPG) concentration and cardiovascular mortality in patients with chronic kidney disease (CKD). This systematic review and meta-analysis aims to investigate the association between OPG concentration and cardiovascular mortality in patients with CKD. Methods: Between January 1970 and February 2020, the PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies investigating the association between OPG concentration and cardiovascular mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using random effects models. Results: In total, 10 studies comprising 2,120 patients (including 1,723 receiving dialysis) with CKD were included. The included studies were considered to be of fair to high quality. Patients in the highest OPG concentration group had a significantly higher risk of cardiovascular mortality (4 studies; adjusted HR, 2.05; 95% CI, 1.39–3.00) than patients in the low OPG concentration group. An increase of 1 pmol/L in OPG concentration was associated with a 4% increased risk of cardiovascular mortality (6 studies; adjusted HR, 1.04; 95% CI, 1.02–1.07). Conclusion: Elevated OPG concentrations are associated with an increased risk of cardiovascular death in patients with CKD.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Demetria Hubbard ◽  
Lisandro D. Colantonio ◽  
Robert S. Rosenson ◽  
Todd M. Brown ◽  
Elizabeth A. Jackson ◽  
...  

Abstract Background Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). Methods We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. Results Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90–0.95), 0.89 (95%CI: 0.85–0.93), and 1.18 (95%CI: 1.14–1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. Conclusion Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.


2021 ◽  
Vol 6 (1) ◽  
pp. e000672
Author(s):  
Ryan Pratt ◽  
Mete Erdogan ◽  
Robert Green ◽  
David Clark ◽  
Amanda Vinson ◽  
...  

BackgroundThe risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.ObjectivesTo characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.MethodsAll major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.ResultsIn total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p<0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.ConclusionIndependent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Bakhtawar K Mahmoodi ◽  
Ron T Gansevoort ◽  
Inger Anne Naess ◽  
Pamela L Lutsey ◽  
Sigrid K Braekkan ◽  
...  

Background: Recent findings suggest that mild chronic kidney disease (CKD) might be associated with increased risk of venous thromboembolism (VTE). However, results were partially inconsistent, which may be due to lack of power. We therefore performed a meta-analysis to investigate the association between mild CKD and VTE incidence. Methods: A literature search was performed to retrieve community-based cohorts with information on the association of estimated glomerular filtration rate (eGFR) and albuminuria with VTE. Five cohorts were identified that were pooled on individual level. To obtain pooled hazard ratios (HRs) for VTE, linear spline models were fitted using Cox regression with shared-frailty. Models were adjusted for age, sex, hypertension, total cholesterol, smoking, diabetes, history of cardiovascular disease and body-mass index. Random-effect meta-analysis was used to obtain adjusted pooled HRs of VTE with CKD versus no CKD. Results: The analysis included 95,154 participants with 1,178 VTE cases and 599,453 person-years of follow-up. Risk of VTE increased continuously with lower eGFR and higher ACR (Figure). Compared with eGFR 100 mL/min/1.73m², pooled adjusted HRs for VTE were 1.3 (1.0–1.7) for eGFR 60, 1.8 (1.3–2.6) for 45 and 1.9 (1.2–2.9) for 30 mL/min/1.73m². Compared with albumin-creatinine ratio (ACR) 5 mg/g, pooled adjusted HRs for VTE were 1.3 (1.04–1.7) for ACR 30, 1.6 (1.1–2.4) for 300 and 1.9 (1.2–3.1) for 1000 mg/g. There was no evidence for interaction between eGFR and ACR (P=0.22). The pooled adjusted HR for CKD (eGFR <60 ml/min/1.73m² or albuminuria ≥30 mg/g) vs. no CKD was 1.5 (95%CI, 1.2–2.1). Results were similar for idiopathic and provoked VTE. Conclusion: Both reduced eGFR and elevated albuminuria are novel independent predictors of VTE in the general population.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2907 ◽  
Author(s):  
Weifeng Shang ◽  
Lixi Li ◽  
Yali Ren ◽  
Qiangqiang Ge ◽  
Ming Ku ◽  
...  

Background Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. Methods PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Results Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23–1.76])], with significant heterogeneity among these studies (I2 = 93.6%, P < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. Conclusion A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures.


2021 ◽  
Author(s):  
Kevin C. Maki ◽  
Meredith L. Wilcox ◽  
Mary R. Dicklin ◽  
Rahul Kakkar ◽  
Michael H. Davidson

Abstract Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥ 12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 38 trials with duration ≥ 12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 8 of other types of interventions. All-cause mortality was reported in 116/2385 (4.86%) subjects in intervention groups and 161/2404 (6.70%) subjects in control groups. The pooled RR estimate of the 24 trials ≥ 12 months with ≥ 1 event in ≥ 1 group was 0.72 (95% CI 0.57 to 0.91, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥ 6 months (31 trials), ≥ 9 months (26 trials), and > 12 months (9 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.66, 95% CI 0.38 to 1.15. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.


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