Tyrone G Harrison1, Caley B Shukalek2, Brenda R Hemmelgarn3, Kelly B Zarnke2, Paul E Ronksley4, Nicolas Iragorri5, Michelle M Graham6, Matthew T James7. 1. Departments of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 2. Departments of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 3. Departments of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 4. Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 5. Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 6. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada. 7. Departments of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: mjames@ucalgary.ca.
Abstract
RATIONALE & OBJECTIVE: Use of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) for cardiovascular (CV) risk assessment in patients with end-stage kidney disease (ESKD) remains unclear. We examined the associations between different threshold elevations of these peptide levels and clinical outcomes in patients with ESKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We searched MEDLINE and EMBASE (through September 2019) for observational studies of adults with ESKD (estimated glomerular filtration rate≤15mL/min/1.73m2 or receiving maintenance dialysis). SELECTION CRITERIA FOR STUDIES: Studies that reported NT-proBNP or BNP levels and future CV events, CV mortality, or all-cause mortality. DATA EXTRACTION: Cohort characteristics and measures of risk associated with study-specified peptide thresholds. ANALYTICAL APPROACH: Hazard ratios (HRs) for clinical outcomes associated with different NT-proBNP and BNP ranges were categorized into common thresholds and pooled using random-effects meta-analysis. RESULTS: We identified 61 studies for inclusion in our review (19,688 people). 49 provided sufficient detail for inclusion in meta-analysis. Pooled unadjusted HRs for CV mortality were progressively greater for greater thresholds of NT-proBNP, from 1.45 (95% CI, 0.91-2.32) for levels>2,000pg/mL to 5.95 (95% CI, 4.23-8.37) for levels>15,000pg/mL. Risk for all-cause mortality was significantly higher at all NT-proBNP thresholds ranging from> 1,000 to> 20,000pg/mL (HR range, 1.53-4.00). BNP levels>550pg/mL were associated with increased risk for CV mortality (HR, 2.54; 95% CI, 1.49-4.33), while the risks for all-cause mortality were 2.04 (95% CI, 0.82-5.12) at BNP levels>100pg/mL and 2.97 (95% CI, 2.21-3.98) at BNP levels>550pg/mL. Adjusted analyses demonstrated similarly greater risks for CV and all-cause mortality with greater NT-proBNP concentrations. LIMITATIONS: Incomplete outcome reporting and risk for outcome reporting bias. Estimation of risk for CV events for specific thresholds of both peptides were limited by poor precision. CONCLUSIONS: ESKD-specific NT-proBNP and BNP level thresholds of elevation are associated with increased risk for CV and all-cause mortality. This information may help guide interpretation of NT-proBNP and BNP levels in patients with ESKD.
RATIONALE & OBJECTIVE: Use of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) for cardiovascular (CV) risk assessment in patients with end-stage kidney disease (ESKD) remains unclear. We examined the associations between different threshold elevations of these peptide levels and clinical outcomes in patients with ESKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We searched MEDLINE and EMBASE (through September 2019) for observational studies of adults with ESKD (estimated glomerular filtration rate≤15mL/min/1.73m2 or receiving maintenance dialysis). SELECTION CRITERIA FOR STUDIES: Studies that reported NT-proBNP or BNP levels and future CV events, CV mortality, or all-cause mortality. DATA EXTRACTION: Cohort characteristics and measures of risk associated with study-specified peptide thresholds. ANALYTICAL APPROACH: Hazard ratios (HRs) for clinical outcomes associated with different NT-proBNP and BNP ranges were categorized into common thresholds and pooled using random-effects meta-analysis. RESULTS: We identified 61 studies for inclusion in our review (19,688 people). 49 provided sufficient detail for inclusion in meta-analysis. Pooled unadjusted HRs for CV mortality were progressively greater for greater thresholds of NT-proBNP, from 1.45 (95% CI, 0.91-2.32) for levels>2,000pg/mL to 5.95 (95% CI, 4.23-8.37) for levels>15,000pg/mL. Risk for all-cause mortality was significantly higher at all NT-proBNP thresholds ranging from> 1,000 to> 20,000pg/mL (HR range, 1.53-4.00). BNP levels>550pg/mL were associated with increased risk for CV mortality (HR, 2.54; 95% CI, 1.49-4.33), while the risks for all-cause mortality were 2.04 (95% CI, 0.82-5.12) at BNP levels>100pg/mL and 2.97 (95% CI, 2.21-3.98) at BNP levels>550pg/mL. Adjusted analyses demonstrated similarly greater risks for CV and all-cause mortality with greater NT-proBNP concentrations. LIMITATIONS: Incomplete outcome reporting and risk for outcome reporting bias. Estimation of risk for CV events for specific thresholds of both peptides were limited by poor precision. CONCLUSIONS: ESKD-specific NT-proBNP and BNP level thresholds of elevation are associated with increased risk for CV and all-cause mortality. This information may help guide interpretation of NT-proBNP and BNP levels in patients with ESKD.
Authors: Doris Winitzki; Helena U Zacharias; Jennifer Nadal; Seema Baid-Agrawal; Elke Schaeffner; Matthias Schmid; Martin Busch; Manuela M Bergmann; Ulla Schultheiss; Fruzsina Kotsis; Helena Stockmann; Heike Meiselbach; Gunter Wolf; Vera Krane; Claudia Sommerer; Kai-Uwe Eckardt; Markus P Schneider; Georg Schlieper; Jürgen Floege; Turgay Saritas Journal: Kidney Int Rep Date: 2022-02-14
Authors: Lilian Cordeiro; Walther Yoshiharu Ishikawa; Maria Claudia C Andreoli; Maria Eugenia F Canziani; Luiza Karla R P Araujo; Benedito J Pereira; Hugo Abensur; Rosa M A Moysés; Rosilene M Elias Journal: Sci Rep Date: 2022-09-22 Impact factor: 4.996