NT-proBNP as a Predictive Biomarker for Contrast-Induced Nephropathy in ACS Patients Undergoing Coronary Angiogram – An Observational Study

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INTRODUCTION

Coronary interventions require the usage of iodinated contrast, this in addition to the elderly patient population along with the procedural complexity has increased the incidence of renal dysfunction, known as contrast-induced nephropathy (CIN). The reported incidence of CIN in high-risk patients undergoing CAG lies between 10% and 20%.^[1]

This increased incidence could be attributed to the patient factors including geriatric group of patients, history of diabetes and chronic kidney disease, or procedure related factors such as intra-arterial route of administration, use of high osmolar contrast agents, repeated exposure to contrast agents within 48 h, and volume of contrast used.^[2] The prevention of CIN is of prime significance, with rising cases of CAGs and PCIs.

CIN is defined as an absolute increase in serum creatinine of ≥0.5 mg/dL (44.2 µmol/L) or a ≥25% relative increase in serum creatinine from the baseline value at 48–72 h after exposure to contrast agents in the absence of alternative causes for acute kidney injury (AKI).^[3,4]

Risk-score models such as Mehran CIN score and BMC2 CIN score are being increasingly used bedside as a guide in predicting and preventing the said complication. These scores are lacking in quantitative biomarkers which predict multi-organ dysfunction. Such an objective test, in addition to these risk score models, performed at admission, before the coronary interventions would better aid in preventing CIN. N-terminal pro-brain natriuretic peptide (NT-proBNP) is one such biomarker which is easily available. It is associated with increasing age, heart failure, diabetes, renal disease, and geriatric patients which are risk factors for CIN.^[5,6] There is evidence of measurement of serum BNP at admission aiding in identification of patients at risk of developing CIN after primary PCI.^[7] The purpose of this study is to determine the value of baseline NT-proBNP as a predictive biomarker in development of CIN for patients undergoing CAG.

MATERIAL AND METHODS

The study included 75 patients more than 20 years age admitted in NIMS cardiology department from period June 2021 to November 2021 with chest pain and established diagnosis of ACS (STEMI, NSTEMI, UNSTABLE ANGINA) not more than 2 week old. Patients with pre-existing renal disease, cardiogenic shock, acute LVF, and age >65 years were excluded from the study. Patients were enrolled in the study after admission and taking a duly informed consent. Serum creatinine and NT-proBNP levels are measured on the day of admission. Nephrotoxic drugs to be stopped on admission.

The formula used for maximum contrast dose: 5 × body weight [kg])/serum creatinine. Modification of Diet in Renal Disease equation was used in calculating Estimated Glomerular Filtration Rate (eGFR). Repeat serum creatinine is measured at 48 h after contrast administration.

The CI-AKI is defined as a relative increase of ≥25% or absolute increase of ≥0.5 mg/dL in creatinine concentrations within 48 h after coronary angiography.

RESULTS

The study is an observational prospective study involving 75 patients belonging to the age group of 57.11 ± 8.25. All patients underwent diagnostic coronary angiography. The study included 72% males and 28% females. Of the total patient population, 32% of them are diabetic (24), 20% of them hypertensive (15), and 29.3% of them smokers. Spearman’s correlation test was used to assess the correlation between NT-proBNP values and EF on the 2D echo. The rho value (−0.69) was suggestive of a strong negative correlation. P < 0.001 making it statistically significant [Table 1].

When simple linear regression analysis was used to predict the NT-proBNP levels by EF percentage among study patients, it showed that, for every 1% decrease in Ejection Fraction, the NT-proBNP levels will significantly increase by 102.90 pg/ml at P < 0.001 and this is accounted by 31% variation in ECHO and EF [Table 2].

Mann–Whitney test was used to compare the risk factors such as diabetes, smoking, hypertension and its probable association with the serum NT-proBNP values in our study and to verify if they contribute as confounding factors. However, the results show P value as not significant [Figure 1].

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Figure 1:

Mean NT-proBNP levels based on presence of DM/HTN/ smoking condition among patients.

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Thus, high values of NT-proBNP serve as a predictor and help in practicing target-guided adequate measures to prevent CIN, in the form of regulating contrast volume, drugs such as N-acetyl-cysteine, and hydration in the predicted at risk patient population [Figure 2].

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Figure 2:

Mean creatinine levels at baseline based on presence of DM/HTN/smoking condition among patients.

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Contrast volume used was 80 ml in approximately 53.3% of patient population and 60 ml in 36%. When Wilcoxon Signed–Rank test was used to compare the baseline serum creatinine values with 48/72 h serum creatinine values after undergoing angiography with contrast, incidence of AKI as shown by the resulting P value was < 0.001, thus statistically significant [Table 3].

The ROC curve analysis to establish the association between NT-proBNP as a marker for incidence of AKI (CIN) shows that, NT-proBNP cutoff >1670 pg/ml has a sensitivity of 81.82% and specify of 98.44% and is statistically significant with P value < 0.001 [Table 4 and Figure 3].

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Figure 3:

ROC curve for NT-proBNP (pg/ml).

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DISCUSSION

NT-proBNP is a neurohormone secreted in response to increased intracardiac volume and pressures, from the myocardium. It is an established biomarker for the left ventricular dysfunction. Mann–Whitney test was used to compare risk factors such as diabetes, hypertension, smoking, and its association with the serum NT-proBNP values in our study and to verify if they contribute as confounding factors. However, the results show p value as not significant. Similar results were found in the study by Liu et al., where contrast volume to creatinine clearance ratio was evaluated and compared to CIN incidence in patients undergoing PCI^[6]

Serum creatinine levels, at both baseline and at 48/72 h when compared in the patient population with comorbidities like diabetes and hypertension and risk factor like smoking has shown to be statistically not significant as indicated by the p value obtained from the mann whitney test. The present study showed a significant association between the high values of NT-proBNP with an increased risk of CIN. Baseline NT-proBNP (before procedure) value of more than 1670 pg/mL, the cutoff value, was a strong and independent predictor of CIN.

A similar study was performed in patients undergoing cardiac surgeries; pre-operative NT-proBNP and its relation with development of post-operative AKI were assessed. In this study by Wang et al., it was observed that post-operative AKI occurred in (34.0%) patients, with Stage 2 AKI in (3.4%) patients, Stage 3 AKI in (1.3%) patients, and new-onset dialysis was required in (0.7%) patients.^[7]

The NT-proBNP concentrations were significantly correlated with all the stages of AKI (P < 0.01). Including NT-proBNP in pre-operative assessment has substantially improved in predicting post-operative AKI.^[7]

Another study by Jarai et al., including a total of 979 patients of ST-segment–elevation myocardial infarction that was enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, also had compared the BNP levels done before primary percutaneous coronary intervention in predicting postoperative incidence of CI-AKI.^[8]

The reason for this association is unclear; however, the potential mechanisms by which elevated NT-proBNP values were associated with incidence of AKI/CIN are hypothesized as follows:

1. Baseline high NT-proBNP values are related to associate risk factors that are independent risk factors for the development of CIN that includes advanced age, diabetes mellitus, hypertension, and smokers. It was observed that high values of NT-proBNP is seen in association with a higher risk of developing end-stage renal disease in diabetics^[9]

2. Renal dysfunction patients have high NT-proBNP values. This may be attributed to either decreased renal clearance or decreased renal responsiveness to BNP.^[10] Studies showed that NT-proBNP values increase with decreasing GFR in patients of cardiac dysfunction. This decreased clearance ability of NT-proBNP is possibly due to impaired renal function.^[11] However, our study excluded CKD patients

3. BNP decreases the effect of catecholamines and generates nitric oxide, which inhibits myocardial contractility, causing vasodilation and renal hypo-perfusion. CIN is a subtype of cardiorenal syndrome type 1. Definition of which is, worsening renal function attributed to acute heart failure that may exacerbate both cardiac and renal impairment.^[12,13]

Recent studies focus on the inflammatory markers and its role in predicting the link between cardiac and renal diseases. The natriuretic peptides are established biomarkers in heart failure and since increased levels can be seen in renal impairment and heart failure, they probably also reflect renal injury.^[14]

Thus, this biomarker useful in predicting both cardiac and renal impairment has the potential as a valuable diagnostic tool.

CONCLUSION

NT-proBNP >1670 pg/mL before the procedure was significantly associated with the risk of development of CIN. Measurement of serum NT-proBNP pre-procedure (coronary angiography) aids in identifying and predicting at risk population for developing AKI/CIN. NT-proBNP value pre procedure serves as a biomarker in predicting risk of development of CIN. We can practice target guided adequate measures (such as, hydration, decreasing contrast volume used and n-acetylcysteine injection) to prevent CIN in such patients with high ntprobnp values.