Growth differentiation factor-15 levels and the risk of contrast induced acute kidney injury in acute myocardial infarction patients treated invasively: A propensity-score match analysis

Abstract

Background: Growth differentiation factor-15 (GDF-15) is an emerging biomarker for risk stratification in cardiovascular disease. Contrast-induced acute kidney injury (AKI) is an important complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). In this retrospectively observational study, we aimed to determine the role of GDF-15 and the risk of AKI in acute myocardial infarction (AMI) patients.

Methods: The medical records of 1195 patients with AMI were reviewed. After exclusion criteria, a total of 751 eligible patients who underwent CAG or PCI were studied. Preoperative clinical parameters including GDF-15 levels were recorded. Multivariate logistic regression analysis was used to identify the risk factors of AKI. Subsequently, to reduce a potential selection bias and to balance differences between the two groups, a propensity score-matched analysis was performed. We recorded the 30-day all-cause mortality of the total study population. Kaplan-Meier analysis was performed to identify the association between short term survival in AMI patients and GDF-15 level.

Results: Among 751 enrolled patients, 106 patients (14.1%) developed AKI. Patients were divided into two groups: AKI group (n = 106) and non-AKI group (n = 645). GDF-15 levels were significantly higher in AKI group compared to non-AKI group (1328.2 ± 349.7 ng/L vs. 1113.0 ± 371.3 ng/L, P <0.001). Multivariate logistic regression analyses showed GDF-15 was an independent risk factor of AKI (per 1000 ng/L increase of GDF-15, OR: 3.740, 95% CI: 1.940-7.207, P < 0.001). According to GDF-15 tertiles, patients were divided into three groups. Patients in middle (OR 2.93, 95% CI: 1.46-5.89, P = 0.003) and highest GDF-15 tertile (OR 3.72, 95% CI: 1.87-7.39, P <0.001) had higher risk of AKI compared to patients in the lowest GDF-15 tertile. The propensity score-matched group set comprised of 212 patients. Multivariate logistic regression revealed that GDF-15 is still an independent risk factor for AKI after matching (per 1000 ng/L increase of GDF-15, OR: 2.395, 95% CI: 1.020-5.626, P = 0.045). Based on the Kaplan-Meier analysis, the risk of 30-day all-cause mortality increased in higher GDF-15 tertiles log rank chi-square: 29.895, P <0.001).

Conclusion: This suggests that preoperative plasma GDF-15 is an independent risk factor of AKI in AMI patients underwent CAG or PCI. GDF-15 and AKI are associated with poor short term survival of AMI patients.

Fig 1. Study flow chart.

AMI = acute myocardial infraction; CAG = coronary angiography; PCI = percutaneous coronary intervention; eGFR = estimated glomerular filtration rate; AKI = acute kidney injury.

Fig 2. Presented are associations between GDF-15 level classified by the tertiles of the distribution and AKI.

T1, the first tertile; T2, the second tertile; T3, the third tertile. Model A = logistic regression model adjusting for adjusted for age, gender, Killip class ≥ 3, diabetes mellitus, serum creatinine, WBC, Neutrophil ratio, HDL-C, anemia, HbA1c ≥ 7.0%, eGFR < 60ml/min/1.73m². Model B = logistic regression model adjusting for Model A plus procedural characteristics (contrast volume > 150 ml, contrast exposure time > 60 min, LAD, LCX, RCA, PCI). T1 (GDF-15 ≤ 893.62 ng/L) T2 (893.62 < GDF-15 ≤ 1307.86 ng/L); T3 (GDF-15 > 1307.86 ng/L).

Fig 3. Presented are probability of AKI performed by logistic regression analyses (male, 70years).

X-axis represents the concentration of serum creatinine, and Y-axis represents the probability of AKI. The blue line represents GDF-15 of 25th percentiles, while the red one represents GDF-15 of 75th percentiles.

Fig 4. ROC analyses of biomarkers to predict AKI.

AUC = area under the curve. AUC of model 3 is 0.816 (95% CI: 0.774–0.859), while AUC of GDF-15 is 0.666 (95% CI: 0.614–0.717), and AUC of creatinine is 0.714 (95% CI: 0.653–0.775). AUC of GDF-15 adjusted by age, gender and eGFR is 0.757 (95% CI: 0.701–0.813). AUC of GDF-15 adjusted by age and serum creatinine is 0.758(95% CI: 0.704–0.812), while AUC of GDF-15 adjusted by age, gender and serum creatinine is 0.761(95% CI: 0.707–0.814). AUC of GDF-15 adjusted by serum creatinine is 0.733(95% CI: 0.680–0.786).

Fig 5. Kaplan Meier analyses of GDF-15 and AKI.

Patients in higher GDF-15 tertile had higher 30-days all-cause mortality risk compared with the middle GDF-15 tertile and lowest GDF-15 tertile (log rank chi-square:29.895, P < 0.001). Patients in AKI group had higher 30-days all-cause mortality risk compared with patients in non-AKI group (log rank chi-square: 97.473, P < 0.001).