Dataset Information

Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis.

ABSTRACT:

Background

Recent 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.

Methods

We 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.

Results

We 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.

Interpretation

Intensive 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.

SUBMITTER: Lv J

PROVIDER: S-EPMC3735743 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis.

Lv Jicheng J Ehteshami Parya P Sarnak Mark J MJ Tighiouart Hocine H Jun Min M Ninomiya Toshiharu T Foote Celine C Rodgers Anthony A Zhang Hong H Wang Haiyan H Strippoli Giovanni F M GF Perkovic Vlado V

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20130624 11

<h4>Background</h4>Recent 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.<h4>Methods</h4>We performed a systematic review and meta-analysis of all relevant reports published between 1950 and July 2011 identified in a search of MEDLINE, Embase an ...[more]

PMID: 23798459

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Project description:Background and objectivesThe Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD.Design, setting, participants, & measurementsWe measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control.ResultsThe mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m2. Median PTH was 48 (interquartile range [IQR], 35-67) pg/ml and FGF23 was 66 (IQR, 52-88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention.ConclusionsSPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.

Project description:BackgroundGuidelines recommend intensive blood pressure (BP) lowering in patients at high risk. While placebo-controlled trials have demonstrated 22% reductions in coronary heart disease (CHD) and stroke associated with a 10-mmHg difference in systolic BP, it is unclear if more intensive BP lowering strategies are associated with greater reductions in risk of CHD and stroke. We did a systematic review to assess the effects of intensive BP lowering on vascular, eye, and renal outcomes.Methods and findingsWe systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and July 2011. We included trials that randomly assigned individuals to different target BP levels. We identified 15 trials including a total of 37,348 participants. On average there was a 7.5/4.5-mmHg BP difference. Intensive BP lowering achieved relative risk (RR) reductions of 11% for major cardiovascular events (95% CI 1%-21%), 13% for myocardial infarction (0%-25%), 24% for stroke (8%-37%), and 11% for end stage kidney disease (3%-18%). Intensive BP lowering regimens also produced a 10% reduction in the risk of albuminuria (4%-16%), and a trend towards benefit for retinopathy (19%, 0%-34%, p = 0.051) in patients with diabetes. There was no clear effect on cardiovascular or noncardiovascular death. Intensive BP lowering was well tolerated; with serious adverse events uncommon and not significantly increased, except for hypotension (RR 4.16, 95% CI 2.25 to 7.70), which occurred infrequently (0.4% per 100 person-years).ConclusionsIntensive BP lowering regimens provided greater vascular protection than standard regimens that was proportional to the achieved difference in systolic BP, but did not have any clear impact on the risk of death or serious adverse events. Further trials are required to more clearly define the risks and benefits of BP targets below those currently recommended, given the benefits suggested by the currently available data.

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.

Project description:ImportanceTrials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown.ObjectivesTo conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5.Data sourcesOvid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases.Study selectionAll RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016.Data extraction and synthesisTwo of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials.Main outcome and measureAll-cause mortality during the active treatment phase of each trial.ResultsThis study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.Conclusions and relevanceRandomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

Project description:BackgroundRandom assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown.Study designLongitudinal subgroup analysis of clinical trial participants.Settings & participantsRandom sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline.Outcomes & measurementsUrine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach.Results978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively.LimitationsExclusion of persons with diabetes, and few participants had advanced CKD.ConclusionsAmong participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Project description:BackgroundLimited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage.MethodsWe randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments.ResultsAmong 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002).ConclusionsThe treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

Dataset Information

Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis.

Background

Methods

Results

Interpretation

Publications

Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis.

Similar Datasets

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