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.

Dickkopf-3 in the prediction of contrast media induced acute kidney injury

“…eGFR was calculated by means of the MDRD formula and AKI was defined according to Acute Kidney Injury Network (AKIN) criteria [ 5 ]. Data about other urinary biomarkers in this population have been published separately, including a detailed description of the baseline parameters of the study population [ 6 ].…”

NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography

“…Initially, some authors [35] only describe that among the group "without CIN" there are individuals with an increase in NGAL similar to that reported in CIN . On the other hand other studies [40,50] suggest a limit as an increase > 25% of the biomarker, or assume that for the diagnosis of subclinical AKI, the biomarker must increase 2 times compared to its baseline levels [41,51]. In the studies of Breglia et al [52] and Rozenfield et al [53], an absolute value is introduced as a reference limit above which the biomarker is reported as positive.…”

NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography

“…Initially, some authors [ 45 ] only describe that among the group “without CIN”, there are individuals with an increase in NGAL similar to that reported in CIN. On the other hand, other studies [ 51 , 59 ] suggest a limit, such as an increase of >25% of the biomarker, or assume that for the diagnosis of subclinical AKI, the biomarker must increase by two times compared to its baseline levels [ 52 , 60 ]. In the studies of Breglia et al [ 61 ] and Rozenfield et al [ 62 ], an absolute value is introduced as a reference limit, above which the biomarker is reported as positive.…”