Dataset Information

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial.

ABSTRACT:

Rationale and objective

In the Systolic Blood Pressure Intervention Trial, the possible relationships between acute kidney injury (AKI) and risk of major cardiovascular events and death are not known.

Study design

Post hoc analysis of a multicenter, randomized, controlled, open-label clinical trial.

Setting and participants

Hypertensive adults without diabetes who were ?50 years of age with prior cardiovascular disease, chronic kidney disease (CKD), 10-year Framingham risk score > 15%, or age > 75 years were assigned to a systolic blood pressure target of < 120 mm Hg (intensive) or < 140 mm Hg (standard).

Predictor

AKI episodes.

Outcomes

The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or cardiovascular death. The secondary outcome was death from any cause. Analytical Approach: AKI was defined using the Kidney Disease: Improving Global Outcomes modified criteria based solely upon serum creatinine. AKI episodes were identified by serious adverse events or emergency room visits. Cox proportional hazards models assessed the risk for the primary and secondary outcomes by AKI status.

Results

Participants were 68 ± 9 years of age, 36% women (3,332/9,361), and 30% Black race (2,802/9,361), and 17% (1,562/9,361) with cardiovascular disease. Systolic blood pressure was 140 ± 16 mm Hg at study entry. AKI occurred in 4.4% (204/4,678) and 2.6% (120/4,683) in the intensive and standard treatment groups respectively (p < 0.001). Those who experienced AKI had higher risk of cardiovascular events (hazard ratio [HR] 1.52, 95% CI 1.05-2.20, p = 0.026) and death from any cause (HR 2.33, 95% CI 1.56-3.48, p < 0.001) controlling for age, sex, race, baseline systolic blood pressure, body mass index, number of antihypertensive medications, cardiovascular disease and CKD status, hypotensive episodes, and treatment assignment.

Limitations

The study was not prospectively designed to determine relationships between AKI, cardiovascular events, and death.

Conclusions

Among older adults with hypertension at high cardiovascular risk, intensive treatment of blood pressure independently increased risk of AKI, which substantially raised risks of major cardiovascular events and death.

SUBMITTER: Dieter BP

PROVIDER: S-EPMC7765707 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial.

Dieter Brad P BP Daratha Kenn B KB McPherson Sterling M SM Short Robert R Alicic Radica Z RZ Tuttle Katherine R KR

American journal of nephrology 20190402 5

<h4>Rationale and objective</h4>In the Systolic Blood Pressure Intervention Trial, the possible relationships between acute kidney injury (AKI) and risk of major cardiovascular events and death are not known.<h4>Study design</h4>Post hoc analysis of a multicenter, randomized, controlled, open-label clinical trial.<h4>Setting and participants</h4>Hypertensive adults without diabetes who were ≥50 years of age with prior cardiovascular disease, chronic kidney disease (CKD), 10-year Framingham risk ...[more]

PMID: 30939480

Similar Datasets

Project description:BACKGROUND:Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN:Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS:9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease. INTERVENTIONS:Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm). OUTCOMES & MEASUREMENTS:Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event. RESULTS:There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively. LIMITATIONS:Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease. CONCLUSIONS:More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study number NCT01206062.

Project description:Rationale & objectiveThe Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).Study designObservational cohort nested in a clinical trial.Setting & participants2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m2 at baseline.ExposureLevels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M) and β2-microglobulin (B2M), uromodulin (UMOD), fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH).OutcomeLongitudinal changes in eGFR and risk of AKI.Analytical approachWe performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.ResultsFrom 10 biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 1-SD higher tubule reserve/mineral metabolism factor score was associated with a 0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors were independently associated with future risk of AKI (per 1 SD higher, HRs of 1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively).LimitationsThe factors require validation in other settings.ConclusionsEFA allows parsimonious subgrouping of biomarkers into factors that are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes.

Project description:Rational & objectiveMany drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain.Study designLongitudinal subgroup analysis of clinical trial participants.Setting & participants2,089 Systolic Blood Pressure Intervention Trial participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline.ExposureSummary score incorporating urine-to-plasma ratios of 10 endogenous secretion markers measured in paired urine and plasma samples at baseline.OutcomeThe primary outcome was longitudinal change in eGFR. Secondary outcomes included chronic kidney disease (CKD) progression (≥50% eGFR decline or incident kidney failure requiring dialysis or kidney transplantation), a cardiovascular disease (CVD) composite (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes), and mortality.Analytical approachLinear mixed-effect models were used to evaluate the association between the secretion score and change in eGFR, and Cox proportional hazards models were used to evaluate associations with CKD progression, CVD, and mortality.ResultsAt baseline, mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.3 years, mean change in eGFR was -1.44% per year, and 72 CKD progression events, 272 CVD events, and 144 deaths occurred. In multivariable analyses, lower secretion score was associated with faster eGFR decline and greater risk of CKD progression, CVD, and mortality. After further adjustment for baseline eGFR and albuminuria, each 1-standard deviation lower secretion score was associated with faster eGFR decline (-0.65% per year; 95% CI, -0.84% to -0.46%), but not CKD progression (HR, 1.23; 95% CI, 0.96-1.58), CVD (HR, 1.02; 95% CI, 0.89-1.18), or mortality (HR, 0.90; 95% CI, 0.74-1.09). The secretion score association with eGFR decline appeared stronger in participants with baseline eGFR <45 mL/min/1.73 m2 (P for interaction < 0.001).LimitationsPersons with diabetes and proteinuria >1 g/d were excluded.ConclusionsAmong SPRINT participants with CKD, lower estimated tubular secretion was associated with faster eGFR decline, independent of baseline eGFR and albuminuria, but not with CKD progression, CVD, or mortality.

Project description:Rationale and objectiveAlthough low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality.Study designLongitudinal analysis of clinical trial participants.Settings and participants7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors.PredictorseGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits.OutcomesThe SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up.Analytical approachCox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18.ResultsMean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up.LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded.ConclusionsIn trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Project description:BackgroundCommunication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making.ObjectivesTo quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001).ConclusionsOver 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated.Trial registrationClinicalTrials.gov Registration: NCT01206062.

Dataset Information

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial.

Rationale and objective

Study design

Setting and participants

Predictor

Outcomes

Results

Limitations

Conclusions

Publications

Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial.

Similar Datasets

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