Acute coronary syndrome (ACS), including unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI), generally results from atherosclerotic plaque rupture or superficial plaque erosion [
Acute kidney injury (AKI) is a common and serious complication of inpatients that causes significant mortality and other severe complications [
Brain natriuretic peptides are released into the circulation in response to myocardial ischemia, pressure overload, or ventricular dilatation [
To fully understand the correlation between elevated levels of brain natriuretic peptide and CI-AKI, we performed this meta-analysis to evaluate the diagnostic value of brain natriuretic peptide for CI-AKI in patients with ACS undergoing coronary angiography.
We conducted this meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement) guidelines [
We reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials Library database through April 2020. The search terms were as follows: (“B-type natriuretic peptide” or “BNP” or “N-terminal pro-B-type natriuretic peptide” or “NT-proBNP”) and (“acute kidney injury” or “AKI” or “contrast-induced acute kidney injury” or “CI-AKI” or “contrast-induced nephropathy” or “CIN”) and (“acute coronary syndrome” or “ACS” or “acute myocardial infarction” or “AMI” or “ST-elevation myocardial infarction” or “STEMI” or “Non–ST elevation myocardial infarction” or “NSTEMI” or “unstable angina”). We did not impose any language restrictions. To find additional citations, the reference lists of the included studies and recent reviews were manually searched when necessary.
Studies were selected if they met the following criteria: a diagnostic value of BNP or NT-proBNP for CI-AKI morbidity in adult patients (≥18 years old) with ACS undergoing coronary angiography or PCI was reported; a 2 × 2 table of results could be constructed; CI-AKI was clearly defined; and the study type was a prospective or retrospective study. The exclusion criteria were as follows: case report, review, editorial, conference abstract, comment, letter, animal study, involving pediatric patients, and insufficient information to extract a 2 × 2 table of results. Two authors (X. L and C. L) assessed the selected studies for the final analysis independently, and any discrepancies were resolved through consultation with the third author (F. Z).
The following data were extracted by two authors (X. L and C. L) and checked by the third author (Z. M): the first author, year of publication, study design, sample size, average age, patient population, definition of CI-AKI, measurement method of brain natriuretic peptide, timing of brain natriuretic peptide measurement, cutoff points, area under the curve (AUC), true positives (TP), true negatives (TN), false positives (FP), false negatives (FN), sensitivity (SEN), and specificity (SPE).
We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) criteria to evaluate each of these studies in 4 domains: patient selection; index test; reference standard; and flow and test timing [
The statistical analyses were conducted by STATA (version 14.0) using the MIDAS module [
As a result of the literature search, 170 studies were identified, of which 55 duplicate publications were excluded. We excluded 101 studies for various reasons by evaluating the titles and abstracts.
The remaining 14 articles were further scrutinized by reading the full text. Four studies were excluded due to an inability to extract a 2 × 2 contingency table [
Flow diagram for the identification of eligible studies.
Table
Characteristics of included studies.
Marker | Study | Study type | Definition of CI-AKI | Population | No. of patients | Male/female | Mean age |
---|---|---|---|---|---|---|---|
BNP | Akgul et al. 2013 [ | Prospective | An absolute increase in SCr of ≥0.3 mg/dl or ≥50% from the baseline | STEMI patients undergoing PCI | 424 | 340/84 | 55.3 ± 12.0 |
Moltrasio et al. 2014 [ | Prospective | An absolute increase in SCr of ≥0.3 mg/dl | ACS patients undergoing PCI | 639 | 484/155 | 70.6 ± 12.5 | |
Tung et al. 2015 [ | Prospective | An absolute increase in SCr of ≥0.3 mg/dl or ≥50% from the baseline | STEMI patients undergoing PCI | 189 | 163/26 | 62.6 ± 13.9 | |
Parenica et al. 2020 [ | Retrospective | An absolute increase in SCr of ≥0.3 mg/dl or ≥50% from the baseline | STEMI patients undergoing PCI | 427 | 328/99 | 73 (45–83) | |
NT-proBNP | Kurtul et al. 2014 [ | Prospective | An increase in SCr of ≥0.5 mg/dL or ≥25% above baseline within 72 hours after contrast administration | ACS patients undergoing PCI | 436 | 280/156 | 62.27 ± 13.01 |
Liu et al. 2016 [ | Prospective | An increase in SCr of >0.5 mg/dL above baseline within 48 to 72 hours after contrast administration | STEMI patients undergoing PCI | 283 | NA | 62.9 ± 12.3 | |
Agarwal et al. 2018 [ | Prospective | An increase in SCr of ≥0.5 mg/dL or ≥25% above baseline within 48 hours after index angiography | ACS patients undergoing PCI | 150 | 96/54 | 63.03 ± 9.07 | |
Kopytsya et al. 2018 [ | Retrospective | An absolute increase in SCr of ≥0.3 mg/dl from the baseline within 48 hours | STEMI patients undergoing SCAG | 68 | NA | NA | |
Alan et al. 2019 [ | Prospective | An absolute increase in SCr of ≥0.3 mg/dl at 48 h of injection or >50% above baseline within 72 hours after contrast administration | ACS patients undergoing coronary angiography | 216 | 170/46 | 63.9 ± 12.3 |
BNP, B-type natriuretic peptide; NT-proBNP, N-terminal pro-B-type natriuretic peptide; CI-AKI, contrast-induced acute kidney injury; SCr, serum creatinine; ACS, acute coronary syndrome; STEMI, ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SCAG, selective coronary angiography; NA, not available;
BNP and NT-proBNP measurements.
Marker | Study | Assay | Optimal timing | Cutoff (pg/ml) | AUC | SEN/SPE, % | TP/FP/TN/FN |
---|---|---|---|---|---|---|---|
BNP | Akgul et al. 2013 [ | Biosite triage meter | On admission | 42.4 | 0.65 | 60/61 | 35/143/223/23 |
Moltrasio et al. 2014 [ | Beckman coulter, triage | On admission | 184 | 0.7 | 79/74 | 67/144/410/18 | |
Tung et al. 2015 [ | Biosite diagnostics, triage | On admission | 676 | 0.86 | 75/89 | 27/17/136/9 | |
Parenica et al. 2020 [ | Enzyme immunoassay, (abbott laboratories) | 12 h after admission | 623 | 0.75 | 57.9/88.2 | 22/46/343/16 | |
NT-proBNP | Kurtul et al. 2014 [ | Elecsys 2010 analyzer, (roche diagnostics) | Before angiography | 2149 | 0.83 | 79.4/74.3 | 50/96/277/13 |
Liu et al. 2016 [ | Electrochemiluminescence immunoassay, (roche diagnostics) | On admission | 1800 | 0.76 | 69/70 | 18/80/178/8 | |
Agarwal 2018 [ | NA | On admission | 2320 | 0.92 | 90.9/81.5 | 20/24/104/2 | |
Kopytsya et al. 2018 [ | Enzyme-like immunoassay | At the 1st day of STEMI. | 1345 | 0.75 | 61.5/94.9 | 14/2/43/9 | |
Alan et al. 2019 [ | NA | NA | 512 | 0.79 | 81/66 | 17/66/129/4 |
BNP, B-type natriuretic peptide; NT-proBNP, N-terminal pro-B-type natriuretic peptide; STEMI, ST-elevation myocardial infarction; AUC, area under curve; SEN, sensitivity; SPE, specificity; TP, true positives; TN, true negatives; FP, false positives; FN, false negatives and NA, not available.
Supplementary material
Deek funnel plot asymmetry test for publication bias, with
The pooled SEN and SPE values were 0.73 (95% CI 0.65–0.79) and 0.79 (95% CI 0.70–0.85), respectively (Figure
Forest plot of the sensitivity and specificity of brain natriuretic peptide for the diagnosis of contrast-induced acute kidney injury in patients with acute coronary syndrome undergoing coronary angiography. The pooled SEN and SPE values were 0.73 (95% CI 0.65–0.79) and 0.79 (95% CI 0.70–0.85), respectively. SEN, sensitivity and SPE, specificity.
Summary receiver operating characteristic curve for the included studies. The AUC of brain natriuretic peptide for the diagnosis of contrast-induced acute kidney injury was 0.81 (95% CI 0.77–0.84), indicating a high diagnostic value. SROC, summary receiver operating characteristic; AUC, area under curve; SEN, sensitivity and SPE, specificity.
Fagan nomogram of brain natriuretic peptide for the diagnosis of contrast-induced acute kidney injury in patients with acute coronary syndrome undergoing coronary angiography. The pretest probability was set to 50%. The use of brain natriuretic peptide for the detection of contrast-induced acute kidney injury increased the posttest probability to 78% when the brain natriuretic peptide results were positive; the posttest probability decreased to 26% when the brain natriuretic peptide results were negative.
A total of 4 studies included patients diagnosed with ACS but not subdivided into UA, STEMI, or NSTEMI and were termed the “ACS” subgroup [
Results of sensitivity analysis and subgroup analysis.
Categories | Number of studies | Sensitivity (95% CI)/ | Specificity (95% CI)/ | AUC (95% CI) | DOR (95% CI) | PLR/NLR |
---|---|---|---|---|---|---|
All studies | 9 [ | 0.73 (0.65, 0.79)/58.95 | 0.79 (0.70, 0.85)/93.92 | 0.81 (0.77, 0.84) | 10 (6, 17) | 3.5/0.35 |
BNP | 4 [ | 0.69 (0.59, 0.78)/72.06 | 0.80 (0.67, 0.89)/97.22 | 0.78 (0.75, 0.82) | 9 (4, 20) | 3.4/0.39 |
NT-proBNP | 5 [ | 0.77 (0.68, 0.83)/43.57 | 0.78 (0.66, 0.87)/84.33 | 0.82 (0.79, 0.85) | 12 (7, 21) | 3.5/0.30 |
STEMI | 5 [ | 0.64 (0.57, 0.71)/9.1 | 0.83 (0.69, 0.92)/97.08 | 0.66 (0.62, 0.70) | 9 (4, 21) | 3.8/0.43 |
ACS | 4 [ | 0.81 (0.74, 0.86)/0 | 0.74 (0.69, 0.78)/69.06 | 0.85 (0.81, 0.88) | 12 (7, 20) | 3.1/0.26 |
Prospective study | 7 [ | 0.76 (0.69, 0.82)/52.08 | 0.74 (0.67, 0.80)/90.41 | 0.82 (0.78, 0.85) | 9 (5, 17) | 2.9/0.32 |
Undergoing PCI | 7 [ | 0.73 (0.65, 0.80)/65.65 | 0.78 (0.70, 0.84)/94.60 | 0.82 (0.78, 0.85) | 10 (5, 17) | 3.3/0.34 |
BNP, B-type natriuretic peptide; NT-proBNP, N-terminal pro-B-type natriuretic peptide; ACS, acute coronary syndrome; STEMI, ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; AUC, area under curve; PLR, positive likelihood ratio; NLR, negative likelihood ratio; DOR, diagnostic odds ratio and CI, credible interval.
The overall
This is the first meta-analysis to evaluate the value of brain natriuretic peptide for CI-AKI in patients with ACS undergoing coronary angiography. Overall, the results suggested that BNP or NT-proBNP is a useful biomarker for the diagnosis of CI-AKI (AUC = 0.81, SEN = 0.73, and SPE = 0.79). The finding applies to both BNP (AUC = 0.78, SEN = 0.69, and SPE = 0.80) and NT-proBNP (AUC = 0.82, SEN = 0.77, and SPE = 0.78).
CI-AKI is a frequent complication in patients who receive iodinated contrast agent [
CI-AKI in ACS is a multifactorial phenomenon. First, the contrast agent is completely excreted by the kidney, and the concentration of the contrast agent increases as it passes through the renal tubules, possibly reaching a level toxic to tubular cells [
BNP or NT-proBNP elevation in AKI patients was found in clinical practice, and recent data suggest that baseline BNP or NT-proBNP may help to identify ACS patients at risk for CI-AKI after coronary angiography. The results from our meta-analysis confirm the role of BNP or NT-proBNP in predicting CI-AKI. Furthermore, we built a Fagan nomogram and a likelihood ratio scattergram to evaluate the clinical application value.
There was considerable heterogeneity among the included studies. Although we conducted sensitivity and subgroup analyses, the heterogeneity was not significantly decreased. This may be caused by different cutoff values, different definitions of CI-AKI, different conditions of patients, or different study designs among the included studies. Some studies measured NT-proBNP, whereas others measured BNP, and the number of participants in the different studies varied greatly, which may also lead to heterogeneity. More high-quality studies are required to shed light on the role of brain natriuretic peptide in the diagnosis of CI-AKI for ACS patients undergoing coronary angiography.
Measuring brain natriuretic peptide is inexpensive, repeatable, and easy to achieve. For patients with ACS, monitoring brain natriuretic peptide is important and essential. Combining brain natriuretic peptide, creatinine, urine output, and other novel biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, which have been identified as potential biomarkers of CI-AKI [
There are several limitations in our meta-analysis. First, the definition of CI-AKI was not completely consistent among the included studies. Second, in terms of sample size, brain natriuretic peptide assays, cutoff values, and study type differed across the included studies, which may have led to heterogeneity. Finally, substantial heterogeneity existed, and additional subgroup analyses could not be performed to reduce and interpret the heterogeneity because a limited number of studies were included in the meta-analysis.
This study is the first meta-analysis to evaluate the diagnostic value of brain natriuretic peptide for CI-AKI in patients with ACS undergoing coronary angiography, and the results suggest that BNP or NT-proBNP can serve as an effective predictive marker for CI-AKI. However, additional high-quality studies are required to find the optimal cutoff value and the diagnostic value of BNP or NT-proBNP in combination with other biomarkers.
Acute coronary syndrome
Acute kidney injury
Area under curve
B-type natriuretic peptide
Contrast-induced acute kidney injury
Credible interval
Diagnostic odds ratio
False negatives
False positives
N-terminal pro-B-type natriuretic peptide
Negative likelihood ratio
Non-ST elevation myocardial infarction
Positive likelihood ratio
Percutaneous coronary intervention
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Quality Assessment of Diagnostic Accuracy Studies-2
Sensitivity
ST-elevation myocardial infarction
Specificity
Summary receiver operating characteristic
True positives
True negatives
Unstable angina.
The data used to support the findings of this study are included within the article and its supplementary material files.
The authors of this manuscript have no relevant conflicts of interest.
XML and CL contributed equally to this work. XML and CL conceived the study, participated in the design, collected the data, performed statistical analyses, and drafted the manuscript. ZM performed statistical analyses and helped to draft the manuscript. RJS and SQ collected the data and revised the manuscript critically for important intellectual content. FHZ collected the data, performed statistical analyses, and helped to revise the manuscript critically for important intellectual content. All authors read and approved the final manuscript.
This work was supported by grants from the Special Scientific Research Project of Military Health Care (17BJZ30).
Supplementary material S1: summary of the methodological quality of the studies according to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) criteria. Supplementary material S2: likelihood ratio scattergram.