Biomarkers in the prediction of contrast media induced nephropathy - the BITCOIN study

Abstract

Background: Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well.

Methods: We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration ≥ 0.3 mg/dl from baseline to day 2-3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations.

Results: 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7-93.1] μg/mg vs. 19.9 [IQR 12.3-38.9] μg/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio <30 mg/g), the NGAL/creatinine ratio was 2.6 higher in CI-AKI vs. no CI-AKI (47.8 [IQR 11.8-75.3] vs. 18.6 [IQR 11.7-36.3] μg/mg). No significant differences were obtained for KIM-1 and calprotectin (p>0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60-0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 μg/mg has a negative predictive value of 96.5%.

Conclusions: The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1

Individual urinary biomarker-creatinine ratios of subjects with and without contrast media induced acute kidney injury (CI-AKI) after coronary angiography for (A) neutrophil gelatinase-associated lipocalin (NGAL), (B) kidney injury molecule-1 (KIM-1), and (C) calprotectin. Data are presented as scatter plots (logarithmic Y-axis, medians and interquartile ranges are indicated by horizontal lines). Significant differences were ***p

Fig 2. Individual urinary biomarker-creatinine ratios of subjects with and without contrast media induced acute kidney injury (CI-AKI) after coronary angiography in the subgroup of patients without clinically overt kidney disease (eGFR > 60 ml, ACR > 30 mg/g creatinine; left column).

Analyses are presented for (A) neutrophil gelatinase-associated lipocalin (NGAL), (B) kidney injury molecule-1 (KIM-1), and (C) calprotectin. Data are presented as scatter plots (logarithmic Y-axis, medians and interquartile ranges are indicated by horizontal lines). Significant differences were ***p

Fig 3

Accuracy of biomarker-creatinine ratios of (A) urinary neutrophil gelatinase-associated lipocalin (NGAL, blue), kidney injury molecule-1 (KIM-1, red) and calprotectin (green) in the prediction of contrast media induced acute kidney injury (CI-AKI) after coronary angiography in receiver operating characteristic (ROC) analysis. The predictive accuracy for CI-AKI in the present study population following the models of Ghani et al. (blue) and Inohara et al. (green) is displayed in (B). ROC curves adding NGAL/creatinine as predictor into the model are displayed in red and black, respectively. AUC–area under the curve. Diagonal scattered lines indicate prediction of CI-AKI by chance.