Calcium channel blockers for people with chronic kidney disease requiring dialysis.
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ABSTRACT:
SUBMITTER: Mugendi GA
PROVIDER: S-EPMC8094736 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to assess the benefits and harms of aldosterone antagonists, both non‐selective (spironolactone) and selective (eplerenone), in comparison to placebo or no intervention or standard care in people with ESKD requiring haemodialysis or peritoneal dialysis.
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Project description:Calcium channel blocker (CCB) or two renin angiotensin aldosterone system blockades (RAAS), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are major potent and prevalently used as initial antihypertensive agents for mild to moderate hypertension, but no uniform agreement as to which antihypertensive drugs should be given for initial therapy, especially among chronic kidney disease (CKD) patients.A systematic review and meta-analysis comparing CCBs and the two RAAS blockades for hypertensive patients with CKD stage 3 to 5D. The inclusion criteria for this systematic review was RCT that compared the effects of CCBs and the two RAAS blockades in patients with hypertension and CKD. The exclusion criteria were (1) renal transplantation, (2) CKD stage 1 or 2, (3) combined therapy (data cannot be extracted separately). Outcomes were blood pressure change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes.21 randomized controlled trials randomized 9,492 patients with hypertensive and CKD into CCBs and the two RAAS blockades treatments. The evidence showed no significant differences in blood presser change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes between CCBs group and the two RAAS blockades group. The publication bias of pooled mean blood presser change that was detected by Egger's test was non-significant.CCBs has similar effects on long term blood pressure, mortality, heart failure, stroke or cerebrovascular events, and renal function to RAAS blockades in patients CKD stage 3 to 5D and hypertension.
| S-EPMC5730188 | 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:This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis.Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications.Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.
| S-EPMC2917467 | biostudies-literature
Project description:Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad biotechnological and therapeutic applications. Here we report a general method for developing novel genetically encoded calcium channel blockers inspired by Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show that diverse cytosolic proteins (CaVβ, 14-3-3, calmodulin and CaMKII) that bind pore-forming α1-subunits can be converted into calcium channel blockers with tunable selectivity, kinetics and potency, simply by anchoring them to the plasma membrane. We term this method 'channel inactivation induced by membrane-tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to small-molecule drug discovery, as engineering FK506-binding protein into intracellular sites within CaV1.2-α1C permits heterodimerization-initiated channel inhibition with rapamycin. The results reveal a universal method for developing novel calcium channel blockers that may be extended to develop probes for a broad cohort of unrelated ion channels.
| S-EPMC4190111 | biostudies-literature
Project description: Not available
| S-EPMC1562493 | biostudies-literature
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.
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Project description:Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model's performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies.
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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.
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