Effects of intensive blood pressure control on mortality and cardiorenal function in chronic kidney disease patients.
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ABSTRACT: Background
Blood pressure (BP) variability is highly correlated with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). However, appropriate BP targets in patients with CKD remain uncertain.Methods
We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of CKD patients who underwent intensive BP management. Kappa score was used to assess inter-rater agreement. A good agreement between the authors was observed to inter-rater reliability of RCTs selection (kappa = 0.77; P = 0.005).Results
Ten relevant studies involving 20 059 patients were included in the meta-analysis. Overall, intensive BP management may reduce the incidence of cardiovascular disease mortality (RR: 0.69, 95% CI: 0.53 to 0.90, P: 0.01), all-cause mortality (RR: 0.77, 95% CI: 0.67 to 0.88, P < 0.01) and composite cardiovascular events (RR: 0.84 95% CI: 0.75 to 0.95, P < 0.01) in patients with CKD. However, reducing BP has no significant effect on the incidence of doubling of serum creatinine level or 50% reduction in GFR (RR: 1.26, 95% CI: 0.66 to 2.40, P = 0.48), composite renal events (RR 1.07, 95% CI: 0.81 to 1.41, P = 0.64) or SAEs (RR: 0.97, 95% CI: 0.90 to 1.05, P = 0.48).Conclusion
In patients with CKD, enhanced BP management is associated with reduced all-cause mortality, cardiovascular mortality, and incidence of composite cardiovascular events.
SUBMITTER: Zhang Y
PROVIDER: S-EPMC8118417 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients.MethodsWe randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years.ResultsDuring the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01).ConclusionsIn overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)
| S-EPMC3662974 | biostudies-literature
Project description:BACKGROUND:More than one-third of US adults have prediabetes, which is typically accompanied by hypertension. METHODS:We examined whether prediabetes modified the effects of intensive systolic blood pressure (SBP) lowering on the incidence of chronic kidney disease (CKD) and acute kidney injury (AKI) events in a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Diabetes was a SPRINT exclusion criterion. We defined normoglycemia and prediabetes as fasting plasma glucose <100 mg/dl and ≥100 mg/dl, respectively. RESULTS:Of the 9,323 participants included in this analysis, 3,898 (41.8%) had prediabetes and the rest (5,425) had normoglycemia. In participants with baseline estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, incident CKD was defined as a ≥30% decline in eGFR to below 60 ml/min/1.73 m2 with repeat confirmation. AKI events were identified clinically. In the non-CKD participants (n = 6,678), there were 164 incident CKD events. The hazard ratios (HRs) for incident CKD for intensive SBP goal (<120 mm Hg) vs. standard SBP goal (<140 mm Hg) in the normoglycemia (HR: 3.25, 95% CI: 2.03, 5.19) and prediabetes (HR: 3.90, 95% CI: 2.17, 7.02) groups were similar (interaction P value 0.64). In the entire analytic cohort (N = 9,323), there were 310 AKI events. AKI HRs for intensive vs. standard SBP in the normoglycemia (HR: 1.59, 95% CI: 1.17, 2.15) and prediabetes (HR: 1.74, 95% CI: 1.22, 2.48) groups were also similar (interaction P value 0.71). CONCLUSIONS:Prediabetes was highly prevalent, but there was no evidence that prediabetes modified the effects of SPRINT intervention on kidney events.CLINICAL TRIALS REGISTRATIONNCT01206062.
| S-EPMC6856623 | biostudies-literature
Project description:BackgroundChronic kidney disease is frequently associated with hypertension and poorly controlled blood pressure can lead to chronic kidney disease progression. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, significantly improves cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes. This analysis explored the relationship between office systolic blood pressure (SBP) and cardiorenal outcomes with finerenone in FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease).MethodsPatients with type 2 diabetes, urine albumin-to-creatinine ratio 30 to 5000 mg/g, and estimated glomerular filtration rate of 25 to <75 mL/min per 1.73 m2 receiving optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. For this analysis, patients (N=5669) were grouped by baseline office SBP quartiles.ResultsFinerenone reduced office SBP across the baseline office SBP quartiles, including patients with baseline office SBP of >148 mm Hg. Overall, patients with lower baseline office SBP quartile and greater declines from baseline in SBP were associated with better cardiorenal outcomes. The risk of primary kidney and key secondary cardiovascular composite outcomes was consistently reduced with finerenone versus placebo irrespective of baseline office SBP quartiles (P for interaction 0.87 and 0.78, respectively). A time-varying analysis revealed that 13.8% and 12.6% of the treatment effect with finerenone was attributed to the change in office SBP for the primary kidney composite outcome and the key secondary cardiovascular outcome, respectively.ConclusionsIn FIDELIO-DKD, cardiorenal outcomes improved with finerenone irrespective of baseline office SBP. Reductions in office SBP accounted for a small proportion of the treatment effect on cardiorenal outcomes.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT02540993.
| S-EPMC9640256 | biostudies-literature
Project description:BackgroundWe sought to assess the risk of acute kidney injury (AKI) and mortality associated with intensive systolic blood pressure reduction in acute intracerebral hemorrhage.Methods and resultsPatients with acute intracerebral hemorrhage had spontaneous cause and symptom onset within 24 hours. We excluded patients with structural causes, coagulopathy, thrombocytopenia, and preexisting end-stage renal disease. We defined AKI using the Acute Kidney Injury Network criteria. Chronic kidney disease status was included in risk stratification and was defined by Kidney Disease Outcomes Quality Initiative staging. Maximum systolic blood pressure reduction was defined over a 12-hour period and dichotomized using receiver operating characteristic curve analysis. Descriptive statistics were done using independent sample t tests, ?2 tests, and Mann-Whitney U tests, whereas multivariable logistic regression analysis was used to evaluate for predictors for AKI and mortality. A total of 448 patients with intracerebral hemorrhage met inclusion criteria. Maximum systolic blood pressure reduction was dichotomized to 90 mm Hg and found to increase the risk of AKI in patients with normal renal function (odds ratio, 2.1; 95% confidence interval, 1.19-3.62; P=0.010) and chronic kidney disease (odds ratio, 3.91; 95% confidence interval, 1.26-12.15; P=0.019). The risk of AKI was not significantly different in normal renal function versus chronic kidney disease groups when adjusted for demographics, presentation characteristics, and medications associated with AKI. AKI positively predicted mortality for patients with normal renal function (odds ratio, 2.41; 95% confidence interval, 1.11-5.22; P=0.026) but not for patients with chronic kidney disease (odds ratio, 3.13; 95% confidence interval, 0.65-15.01; P=0.154).ConclusionsThese results indicate that intensive systolic blood pressure reduction with a threshold >90 mm Hg in patients with acute intracerebral hemorrhage may be an independent predictor for AKI.
| S-EPMC6015439 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. RESULTS:There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). CONCLUSIONS:In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.
| S-EPMC6237052 | biostudies-literature
Project description:BackgroundIn individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear.MethodsSPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP.ResultsMean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events.ConclusionsLow baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.
| S-EPMC5760457 | biostudies-literature
Project description:BackgroundThere is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.MethodsA total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.ResultsAfter 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001).ConclusionsIn patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)
| S-EPMC4123215 | biostudies-literature
Project description:Intensive blood pressure control decreases the rate of cardiovascular events by >25% compared with standard blood pressure control. We sought to determine whether the decrease in cardiovascular events seen with intensive blood pressure control is associated with an increased rate of other causes of hospitalization. This is a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) in 9361 adult participants with hypertension and elevated cardiovascular risk. Participants were randomly assigned to an intensive or standard systolic blood pressure goal (<120 or <140 mm Hg, respectively). The primary outcome was hospitalization rates per 100 person-years for hospitalizations not associated with SPRINT primary events. After excluding hospitalizations linked to SPRINT primary events, there were 4678 participants with a rate of 19.70 hospitalizations per 100 person-years, compared with 4683 participants with a rate of 19.65 (P=0.37). Equivalence testing shows that these hospitalization rates were statistically equivalent at the P=0.05 level. Of those with hospitalizations, >1 hospitalization was seen in 38.8% of intensive arm participants and 41.9% of standard arm participants (P=0.08). The mean cumulative count of nonprimary event hospitalizations was comparable between the two arms. The most common causes of hospitalization were cardiovascular (23.6%) followed by injuries, including bone and joint therapeutic procedures (15.7%), infections (12.0%), and nervous systems disorders (10.7%). No categories of hospitalization were statistically more common in the intensive arm compared with the standard arm. Thus, the decrease in cardiovascular events seen with intensive blood pressure control is not associated with an increased rate of other causes of hospitalization. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.
| S-EPMC7666020 | biostudies-literature
Project description:ImportanceThe optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD).ObjectiveTo compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes.Data sourcesSearches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016.Study selectionRandomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality.Data extraction and synthesisRandom-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity.Main outcomes and measuresDifferences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs.ResultsWe identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control.Conclusions and relevanceTargeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.
| S-EPMC5818822 | biostudies-literature
Project description:BackgroundRecent guidelines suggest lowering the target blood pressure for patients with chronic kidney disease, although the strength of evidence for this suggestion has been uncertain. We sought to assess the renal and cardiovascular effects of intensive blood pressure lowering in people with chronic kidney disease.MethodsWe performed a systematic review and meta-analysis of all relevant reports published between 1950 and July 2011 identified in a search of MEDLINE, Embase and the Cochrane Library. We included randomized trials that assigned patients with chronic kidney disease to different target blood pressure levels and reported kidney failure or cardiovascular events. Two reviewers independently identified relevant articles and extracted data.ResultsWe identified 11 trials providing information on 9287 patients with chronic kidney disease and 1264 kidney failure events (defined as either a composite of doubling of serum creatinine level and 50% decline in glomerular filtration rate, or end-stage kidney disease). Compared with standard regimens, a more intensive blood pressure-lowering strategy reduced the risk of the composite outcome (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.68-0.98) and end-stage kidney disease (HR 0.79, 95% CI 0.67-0.93). Subgroup analysis showed effect modification by baseline proteinuria (p = 0.006) and markers of trial quality. Intensive blood pressure lowering reduced the risk of kidney failure (HR 0.73, 95% CI 0.62-0.86), but not in patients without proteinuria at baseline (HR 1.12, 95% CI 0.67-1.87). There was no clear effect on the risk of cardiovascular events or death.InterpretationIntensive blood pressure lowering appears to provide protection against kidney failure events in patients with chronic kidney disease, particularly among those with proteinuria. More data are required to determine the effects of such a strategy among patients without proteinuria.
| S-EPMC3735743 | biostudies-literature