Aldosterone antagonists for people with chronic kidney disease requiring dialysis
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ABSTRACT:
SUBMITTER: Hasegawa T
PROVIDER: S-EPMC6513429 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8094170 | biostudies-literature
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| S-EPMC8094736 | biostudies-literature
Project description:BackgroundIntradialytic hypotension (IDH) is a common complication of haemodialysis (HD), and a risk factor of cardiovascular morbidity and death. Several clinical studies suggested that reduction of dialysate temperature, such as fixed reduction of dialysate temperature or isothermal dialysate using a biofeedback system, might improve the IDH rate.ObjectivesThis review aimed to evaluate the benefits and harms of dialysate temperature reduction for IDH among patients with chronic kidney disease requiring HD, compared with standard dialysate temperature.Search methodsWe searched Cochrane Kidney and Transplant's Specialised Register up to 14 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.Selection criteriaAll randomised controlled trials (RCTs), cross-over RCTs, cluster RCTs and quasi-RCTs were included in the review.Data collection and analysisTwo authors independently extracted information including participants, interventions, outcomes, methods of the study, and risks of bias. We used a random-effects model to perform quantitative synthesis of the evidence. We assessed the risks of bias for each study using the Cochrane 'Risk of bias' tool. We assessed the certainty of evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE).Main resultsWe included 25 studies (712 participants). Three studies were parallel RCTs and the others were cross-over RCTs. Nineteen studies compared fixed reduction of dialysate temperature (below 36°C) and standard dialysate temperature (37°C to 37.5°C). Most studies were of unclear or high risk of bias. Compared with standard dialysate, it is uncertain whether fixed reduction of dialysate temperature improves IDH rate (8 studies, 153 participants: rate ratio 0.52, 95% CI 0.34 to 0.80; very low certainty evidence); however, it might increase the discomfort rate compared with standard dialysate (4 studies, 161 participants: rate ratio 8.31, 95% CI 1.86 to 37.12; very low certainty evidence). There were no reported dropouts due to adverse events. No study reported death, acute coronary syndrome or stroke.Three studies compared isothermal dialysate and thermoneutral dialysate. Isothermal dialysate might improve the IDH rate compared with thermoneutral dialysate (2 studies, 133 participants: rate ratio 0.68, 95% CI 0.60 to 0.76; I2 = 0%; very low certainty evidence). There were no reports of discomfort rate (1 study) or dropouts due to adverse events (2 studies). No study reported death, acute coronary syndrome or stroke.Authors' conclusionsReduction of dialysate temperature may prevent IDH, but the conclusion is uncertain. Larger studies that measure important outcomes for HD patients are required to assess the effect of reduction of dialysate temperature. Six ongoing studies may provide much-needed high quality evidence in the future.
| S-EPMC6609546 | biostudies-literature
Project description:The incidence and prevalence of chronic kidney disease (CKD), with diabetes and hypertension accounting for the majority of cases, is on the rise, with up to 160 million individuals worldwide predicted to be affected by 2020. Given that current treatment options, primarily targeted at the renin-angiotensin system, only modestly slow down progression to end-stage renal disease, the urgent need for additional effective therapeutics is evident. Endothelin-1 (ET-1), largely through activation of endothelin A receptors, has been strongly implicated in renal cell injury, proteinuria, inflammation, and fibrosis leading to CKD. Endothelin receptor antagonists (ERAs) have been demonstrated to ameliorate or even reverse renal injury and/or fibrosis in experimental models of CKD, whereas clinical trials indicate a substantial antiproteinuric effect of ERAs in diabetic and nondiabetic CKD patients even on top of maximal renin-angiotensin system blockade. This review summarizes the role of ET in CKD pathogenesis and discusses the potential therapeutic benefit of targeting the ET system in CKD, with attention to the risks and benefits of such an approach.
| S-EPMC4216619 | biostudies-other
Project description:BackgroundPatients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m2]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5.MethodsThis was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5.ResultsA total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status.ConclusionsCKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT01985360.
| S-EPMC9588677 | biostudies-literature
Project description:AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis.
| S-EPMC4145550 | biostudies-literature
Project description:IntroductionAfter dialysis-requiring acute kidney injury (AKI-D), recovery of sufficient kidney function to discontinue dialysis is an important clinical and patient-oriented outcome. Predicting the probability of recovery in individual patients is a common dilemma.MethodsThis cohort study examined all adult members of Kaiser Permanente Northern California who experienced AKI-D between January 2009 and September 2015 and had predicted inpatient mortality of <20%. Candidate predictors included demographic characteristics, comorbidities, laboratory values, and medication use. We used logistic regression and classification and regression tree (CART) approaches to develop and cross-validate prediction models for recovery.ResultsAmong 2214 patients with AKI-D, mean age was 67.1 years, 40.8% were women, and 54.0% were white; 40.9% of patients recovered. Patients who recovered were younger, had higher baseline estimated glomerular filtration rates (eGFR) and preadmission hemoglobin levels, and were less likely to have prior heart failure or chronic liver disease. Stepwise logistic regression applied to bootstrapped samples identified baseline eGFR, preadmission hemoglobin level, chronic liver disease, and age as the predictors most commonly associated with coming off dialysis within 90 days. Our final logistic regression model including these predictors had a correlation coefficient between observed and predicted probabilities of 0.97, with a c-index of 0.64. An alternate CART approach did not outperform the logistic regression model (c-index 0.61).ConclusionWe developed and cross-validated a parsimonious prediction model for recovery after AKI-D with excellent calibration using routinely available clinical data. However, the model's modest discrimination limits its clinical utility. Further research is needed to develop better prediction tools.
| S-EPMC6451155 | biostudies-literature
Project description:Background and Purpose. Cardiovascular disease is the major cause of death in dialysis patients. Although aldosterone antagonists were considered a treatment for severe heart failure patients to reduce cardiac mortality, whether treating patients undergoing maintenance dialysis with aldosterone antagonists could reduce the risk of cardiocerebrovascular (CCV) remains unclear. We aim to systematically assess the efficacy and tolerability of the addition of aldosterone antagonists to conventional therapy in patients undergoing maintenance dialysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), and the China National Knowledge Infrastructure (CNKI) for relevant articles. The primary endpoint of interest was CCV mortality. The secondary endpoints were all-cause mortality, left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). Publication bias was evaluated using funnel plots and Egger's test. The meta-analysis was performed using Review Manager software version 5.3. Results. This analysis included 10 randomized controlled trials (RCTs) with 1172 total chronic dialysis patients. The use of aldosterone antagonists in the dialysis population resulted in a marked reduction in CCV mortality (RR 0.42, 95% CI 0.26-0.65, P=0.0002) and all-cause mortality (RR0.46, 95%CI 0.32-0.66, P<0.0001). The LVEF was improved by treatment with aldosterone antagonists (WMD 6.35%, P<0.00001). Moreover, aldosterone antagonists decreased the LVMI (WMD -8.69 g/m2, P=0.0006), whereas aldosterone antagonists increased the occurrence of hyperkalemia (RR1.70, 95%CI 1-2.88, P=0.05) and gynecomastia (RR 8.01, 95% CI 2.44- 26.27, P=0.0006). Conclusions. Addition of aldosterone antagonists to conventional treatment in chronic dialysis patients may reduce CCV mortality, improve cardiac function, and simultaneously decrease LVMI.
| S-EPMC6421009 | biostudies-literature
Project description:This article presents a dataset of body composition in chronic kidney disease (CKD) non-dialysis-dependent (NDD), hemodialysis (HD) and peritoneal dialysis (PD) (for at least 3 months), and kidney transplantation (KTx) (for at least 6 months) patients. The data were collected as part of a PhD research project, an observational cross-sectional study followed by a prospective analysis (about 6 months later). Adult CKD patients (18≤age≤60 years old) from a tertiary hospital were recruited: CKD in stages 3b to 5 for NDD patients; PD patients without peritonitis in the last 30 days; HD patients in 4-hour dialysis session, 3 times per week, through an arteriovenous fistula; and KTx patients with CKD in stages 1 to 3a. Patients with presence of amputated limbs or an electronic implant, wheelchair user or inpatient, body weight above 140 kg or BMI higher than 40 kg/m2, acute infections, cancer diagnosis, acquired immunodeficiency syndrome, and others that could alter body composition were excluded. The dataset in this publication consist of some clinical measurements for characterization of the sample, body composition measurements by dual-energy X-ray absorptiometry and by bioelectrical impedance spectroscopy in tetra-polar whole-body wrist to ankle (BISWB) and segmental (BISSEG) protocols of 266 CKD patients, being 137 men and 129 women; 81 in NDD treatment, 83 in HD, 24 in PD, and 80 in KTx. Measurements were performed consecutively by the same professional after an 8-hour fast, empty urinary bladder, drainage of the peritoneal dialysate, and just after the midweek hemodialysis session. To analyze differences among subgroups according to sex and CKD treatment, unpaired T test or ANOVA and Chi-square, adjusted by Bonferroni post-test, were applied. Agreement in fat free mass and fat mass measurements between BISWB and BISSEG, for cross-sectional data and for body composition changes (prospective measurement - cross-sectional measurement), was checked using intraclass correlation coefficient and 95% confidence intervals. Agreement on individual level was evaluated using the Bland-Altman method with limits of agreement. The data can be valuable in the study of body composition in CKD under all types of treatment and also for agreement analysis among body composition measurements by different instruments and techniques. The data are analysed and interpreted in the research article Bellafronte et al., 2020 [1].
| S-EPMC7721620 | biostudies-literature
Project description:Numerous pre-clinical studies have implicated endothelin-1 in the pathogenesis of diabetic and non-diabetic chronic kidney disease (CKD). Renal endothelin-1 production is almost universally increased in kidney disease. The pathologic effects of endothelin-1, including vasoconstriction, proteinuria, inflammation, cellular injury and fibrosis, are likely mediated by the endothelin A (ETA) receptor. ETA antagonism alone, and/or combined ETA/B blockade, reduces CKD progression. Based on the strong pre-clinical data, several clinical trials using ETA antagonists were conducted. Small trials involving acute intravenous endothelin receptor blockade suggest that ETA, but not ETB, blockade exerts protective renal and vascular effects in CKD patients. A large phase 3 trial (ASCEND) examined the effects of avosentan, an endothelin receptor antagonist, on renal disease progression in diabetic nephropathy. Proteinuria was reduced after 3-6 months of treatment. However the study was terminated due to increased morbidity and mortality associated with avosentan-induced fluid retention. Several phase 2 trials using avosentan at lower doses than in ASCEND, atrasentan or sitaxsentan (the latter two being highly ETA-selective) showed reductions in proteinuria on top of renin-angiotensin system blockade. Infrequent and clinically insignificant fluid retention was observed at the most effective doses. Additional trials using ETA blockers are ongoing or being planned in patients with diabetic nephropathy or focal segmental glomerulosclerosis. Moving forward, such studies must be conducted with careful patient selection and attention to dosing in order to minimize adverse side effects. Nonetheless, there is cause for optimism that this class of agents will ultimately prove to be effective for the treatment of CKD.
| S-EPMC3791980 | biostudies-other