Results and lessons from the Spironolactone To Prevent Cardiovascular Events in Early Stage Chronic Kidney Disease (STOP-CKD) randomised controlled trial.
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SUBMITTER: Ng KP
PROVIDER: S-EPMC4769397 | biostudies-other | 2016 Feb
REPOSITORIES: biostudies-other
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Project description:BackgroundChronic kidney disease is associated with increased arterial stiffness even in the early stages and this is thought to be a key mediator in the pathophysiology of the increased cardiovascular risk associated with this condition. The use of low-dose spironolactone has previously been shown to improve arterial stiffness and reduce left ventricular mass safely in early-stage chronic kidney disease in the context of careful monitoring at a university hospital. However, the majority of patients with chronic kidney disease are managed by their general practitioners in the community. It is not known whether similar beneficial effects can be achieved safely using spironolactone in the primary care setting. The aim of this study is to determine whether low-dose spironolactone can safely lower arterial stiffness in patients with stage 3 chronic kidney disease in the primary care setting.Methods/designSTOP-CKD is a multicentre, prospective, randomized, double-blind, placebo-controlled pilot trial of 240 adult patients with stage 3 chronic kidney disease recruited from up to 20 general practices in South Birmingham, England. Participants will be randomly allocated using a secured web-based computer randomization system to receive either spironolactone 25 mg once daily or a matching inactive placebo for 40 weeks, followed by a wash-out period of 6 weeks. Investigators, outcome assessors, data analysts and participants will all be blinded to the treatment allocation. The primary endpoint is improved arterial stiffness, as measured by carotid-femoral pulse wave velocity between baseline and 40 weeks. The secondary endpoints are incidence of hyperkalaemia, change in estimated glomerular filtration rate, change in urine albumin:creatinine ratio, change in brachial blood pressure, change in pulse waveform characteristics and overall tolerability of spironolactone. An additional quality control study, aiming to compare the laboratory serum potassium results of samples processed via two methods (utilizing routine transport or centrifugation on site before rapid transport to the laboratory) for 100 participants and a qualitative research study exploring patients' and general practitioners' attitudes to research and the use of spironolactone in chronic kidney disease in the community setting will be embedded in this pilot study.Trial registrationCurrent Controlled Trials ISRCTN80658312.
| S-EPMC4113230 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic BP treatment (target <120 mm Hg) was associated with fewer cardiovascular events and higher incidence of kidney function decline compared with standard treatment (target <140 mm Hg). We evaluated the association between mean arterial pressure reduction, kidney function decline, and cardiovascular events in patients without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We categorized patients in the intensive treatment group of the SPRINT according to mean arterial pressure reduction throughout follow-up: <20, 20 to <40, and ?40 mm Hg. We defined the primary outcome as kidney function decline (?30% reduction in eGFR to <60 ml/min per 1.73 m2 on two consecutive determinations at 3-month intervals), and we defined the secondary outcome as cardiovascular events. In a propensity score analysis, patients in each mean arterial pressure reduction category from the intensive treatment group were matched with patients from the standard treatment group to calculate the number needed to treat regarding cardiovascular events and the number needed to harm regarding kidney function decline. RESULTS:In the intensive treatment group, 1138 (34%) patients attained mean arterial pressure reduction <20 mm Hg, 1857 (56%) attained 20 to <40 mm Hg, and 309 (9%) attained ?40 mm Hg. Adjusted hazard ratios for kidney function decline were 2.10 (95% confidence interval, 1.22 to 3.59) for mean arterial pressure reduction between 20 and 40 mm Hg and 6.22 (95% confidence interval, 2.75 to 14.08) for mean arterial pressure reduction ?40 mm Hg. In propensity score analysis, mean arterial pressure reduction <20 mm Hg presented a number needed to treat of 44 and a number needed to harm of 65, reduction between 20 and <40 mm Hg presented a number needed to treat of 42 and a number needed to harm of 35, and reduction ?40 mm Hg presented a number needed to treat of 95 and a number needed to harm of 16. CONCLUSIONS:In the intensive treatment group of SPRINT, larger declines in mean arterial pressure were associated with higher incidence of kidney function decline. Intensive treatment seemed to be less favorable when a larger reduction in mean arterial pressure was needed to attain the BP target.
| S-EPMC5753311 | biostudies-other
Project description:Background and objectivesUromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.Design, setting, participants, & measurementsWe measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication.ResultsThe mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m2, and 78% had eGFR <60 ml/min per 1.73 m2. Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile.ConclusionsHigher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD.Clinical trial registry name and registration numberDeutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.
| S-EPMC7269219 | biostudies-literature
Project description:ObjectiveLower limb complications are major adverse events in patients with peripheral artery disease (PAD) and chronic kidney disease (CKD). These complications can lead to morbidity, disability, reduced quality of life, and higher health care costs. We sought to determine how interim lower limb complications modify the subsequent risk of progression to kidney failure, all-cause mortality before kidney failure, and cardiovascular (CV) events in a cohort of patients with CKD stages G3 to G5.MethodsWe performed a retrospective cohort study using patient-level data obtained by linking several administrative databases from Manitoba, Canada. We used Fine and Gray regression models for the primary outcomes of (1) kidney failure adjusted for the competing risk of all-cause mortality, (2) death before kidney failure, and (3) cardiovascular-related hospitalization with the competing risk of non-CV death.ResultsA total of 92,618 patients were included in the final cohort, with a median follow-up time of 2.56 years. Compared with patients who did not experience an interim lower limb complication, there was a higher risk of kidney failure (adjusted hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.10-3.00), all-cause mortality before kidney failure (adjusted HR 2.73, 95% CI 2.55-2.92), and CV events (adjusted HR 2.12, 95% CI 1.90-2.38).ConclusionsInterim lower limb complications are associated with an increased risk of kidney failure, all-cause mortality before kidney failure, and cardiovascular-related hospitalization. Clinical trials of screening and treatment strategies for patients with CKD at risk for lower limb complications may help determine optimal strategies to manage this risk.
| S-EPMC7879126 | biostudies-literature
Project description:BackgroundHyperphosphatemia and calcium load were associated with vascular calcification. The role of calcium-containing phosphate binders (CCPBs) use as important determinants of death and cardiovascular events in predialysis hyperphosphatemic chronic kidney disease (CKD) patients remain unclear due to the absence of evidence for reduced mortality with CCPB use compared with placebo. We aimed to investigate the effect of using CCPBs or nonuse in all-cause mortality rates and cardiovascular events in CKD stage 5 patients between 2000 and 2005 in the Taiwanese National Health Insurance Research Database.MethodsPatients with known coronary heart disease and those who had undergone dialysis or renal transplantation were excluded. The CCPB users were matched with nonusers by the propensity score model. Multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) of all-cause mortality and cardiovascular events.ResultsDuring a mean follow-up of 4.58 years, 879 CCPB users were matched with 3516 nonusers. CCPB use was an independent risk factor for cardiovascular events [adjusted hazard ratio (HR) 1.583, 95% confidence interval (CI) 1.393-1.799]. The increased cardiovascular risk was dose-dependent and consistent across all subgroup analyses. Compared with no use, CCPB use was associated with no significant all-cause mortality risk (1.74 vs. 1.75 events per 100 person-years, adjusted HR 0.964, 95% CI 0.692-1.310).ConclusionsCCPB use in CKD stage 5 patients was associated with a significantly increased cardiovascular event risk compared with the nonusers, whereas the all-cause mortality risk was similar between the two groups. Whether these relationships are causal require further randomized controlled trials.
| S-EPMC7598463 | biostudies-literature
Project description:BackgroundThe prevalence of chronic kidney disease (CKD) is increasing globally. Early diagnosis in primary care may have a role in ensuring proper intervention. We aimed to determine the prevalence and outcome of CKD in primary care.MethodsWe performed an observational cohort study in primary care in Copenhagen (2001-2015). Outcomes were stroke, myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), all-cause- and cardiovascular mortality. We combined individuals with normal kidney function and CKD stage 2 as reference. We conducted cause-specific Cox proportional regressions to calculate the hazard ratios for outcomes according to CKD group. We explored the associations between kidney function and the outcomes examined using eGFR as a continuous variable modelled with penalised splines. All models were adjusted for age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol and use of antihypertensive treatment.ResultsWe included 171,133 individuals with at least two eGFR measurements of which the majority (n = 157,002) had eGFR > 60 ml/min/1.73m2 at index date, and 0.05% were in CKD stage 5. Event rates were low in eGFR > 60 ml/min/1.73m2 but increased in those with higher stages of CKD. In adjusted analyses we observed an increase in hazard rates for every outcome with every increment in CKD stage. Compared to the reference group, individuals in CKD stage 4 had double the hazard rate of PAD, MI, cardiovascular and all-cause mortality.ConclusionsOur data from a large primary care cohort demonstrate an early increase in the risk of adverse outcomes already at CKD stage 3. This underlines the importance of studying early intervention in primary care.
| S-EPMC10286349 | biostudies-literature
Project description:BackgroundChronic kidney disease is a known risk factor for end-stage renal and cardiovascular diseases. However, data are limited on the causes of hospitalization in patients with chronic kidney disease of maintenance period. This study aimed to aggregate hospitalization data of CKD patients and to determine the high-risk population. In addition, we compared CKD population to general population.MethodsWe conducted a post hoc analysis of the chronic kidney disease-Japan cohort study, a multicenter prospective cohort study of 2966 patients with chronic kidney disease with a median 3.9 years of follow-up. We examined the hospitalization reasons and analyzed the risk factors.ResultsWe found 2897 all-cause hospitalization events (252.3 events/1000 person-years), a hospitalization incidence 17.1-fold higher than that in an age- and sex-matched cohort from the general Japanese population. Kidney, eye and adnexa, and heart-related hospital admissions were the most common. All-cause hospitalization increased with chronic kidney disease stage and with the presence of diabetes. Patients with diabetes at enrollment had 345.7 hospitalization events/1000 person-years, which is considerably higher than 196.8 events/1000 person-years for those without diabetes. Survival analysis, using hospitalization as an event, showed earlier all-cause hospitalization with the progression of chronic kidney disease stage and diabetes. Cardiovascular disease hospitalizations were more strongly influenced by diabetes than chronic kidney disease stage.ConclusionsPatients with chronic kidney disease and diabetes are highly vulnerable to hospitalization for a variety of diseases. These descriptive data can be valuable in predicting the prognosis of patients with chronic kidney disease.
| S-EPMC6555784 | biostudies-literature
Project description:Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high-sensitivity hs-CRP (C-reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all-cause mortality. The secondary end points were separate outcomes of eMACE, all-cause death, and adverse kidney outcome. We also evaluated predictive ability of hs-CRP for the primary outcome. The median hs-CRP level was 0.60 mg/L. During the mean follow-up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs-CRP with the primary outcome. The hazard ratios for hs-CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87-2.03) and 2.08 (95% CI, 1.30-3.33) compared with the hs-CRP of <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all-cause death; however, hs-CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs-CRP compared with conventional factors. Conclusions In Korean patients with chronic kidney disease, the hs-CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs-CRP did not associate with adverse kidney outcome, and the predictive performance of hs-CRP was not strong. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01630486.
| S-EPMC7763415 | biostudies-literature
Project description:An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44±15 ml/min per 1.73 m(2)). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to 1.40]; HR for highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.
| S-EPMC3904568 | biostudies-literature
Project description:As non-high-density lipoprotein cholesterol (non-HDL-C) levels account for all atherogenic lipoproteins, serum non-HDL-C level has been suggested to be a marker for cardiovascular (CV) risk stratification. Therefore, to unveil the association of serum non-HDL-C levels with CV outcomes in patients with non-dialysis chronic kidney disease (ND-CKD), the patients at stages 1 to 5 (n = 2152) from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into quintiles by serum non-HDL-C level. The primary outcome was a composite of all-cause death or non-fatal CV events. The median duration of follow-up was 6.940 years. The analysis using the Cox proportional hazard model unveiled that the composite CV event was significantly increased in the 5th quintile (adjusted hazard ratio 2.162, 95% confidence interval 1.174 to 3.981), compared to that of the 3rd quintile. A fully adjusted cubic spline model depicted a non-linear, J-shaped association between non-HDL-C and the risk of a composite CV event. The association remained robust in a series of sensitivity analyses, including the analysis of a cause-specific hazard model. Subgroup analyses reveled that the association is not significantly altered by clinical conditions, including age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, high serum non-HDL-C level increased the risk of adverse CV outcomes among the patients with ND-CKD. Further studies are warranted to define the optimal target range of non-HDL-C levels in this population.
| S-EPMC9505887 | biostudies-literature