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

Abstract

Background Dickkopf-3 (DKK3) has recently been discovered as a urinary biomarker for the prediction of acute kidney injury (AKI) after cardiac surgery. This finding needs to be confirmed for AKI in other clinical settings. The present study investigates whether DKK3 can predict contrast-induced AKI (CI-AKI). Methods We performed a prospective study in 490 patients undergoing coronary angiography. Primary endpoint was an increase in serum creatinine concentration ≥ 0.3 mg/dl within 72 h after the procedure. DKK3 was assessed < 24 h before coronary angiography. Predictive accuracy was assessed by receiver operating characteristic (ROC) curves. Results CI-AKI was observed in 30 (6.1%) patients, of whom 27 corresponded to stage I and 3 to stage II according to the Acute Kidney Injury Network (AKIN) criteria. Subjects who developed CI-AKI had a 3.8-fold higher urinary DKK3/creatinine ratio than those without CI-AKI (7.5 pg/mg [interquartile range [IQR] 1.2–1392.0] vs. 2.0 pg/mg [IQR 0.9–174.0]; p = 0.047). ROC analysis revealed an area under the curve (AUC) of 0.61. Among subjects without clinically overt chronic kidney disease (estimated glomerular filtration rate [eGFR] > 60 ml/min, urinary albumin creatinine ratio < 30 mg/g), the DKK3/creatinine ratio was 5.4-fold higher in those with subsequent CI-AKI (7.5 pg/mg [IQR 0.9–590.1] vs. 1.38 pg/mg [IQR 0.8–51.0]; p = 0.007; AUC 0.62). Coronary angiography was associated with a 43 times increase in the urinary DKK3/creatinine ratio. Conclusions Urinary DKK3 is an independent predictor of CI-AKI even in the absence of overt chronic kidney disease (CKD). The study thereby expands the findings on DKK3 in the prediction of postoperative loss of kidney function to other entities of AKI. Graphic abstract

Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review

“…uDKK3 baseline levels were significantly higher in individuals that developed AKI. However, follow-up uDKK3 levels were not higher in individuals that developed AKI 23 . In a second study on 458 patients scheduled for cardiovascular procedures requiring contrast medium administration baseline uDKK3 to creatinine ratio was predictive for the development of AKI and persistent kidney dysfunction with thresholds of > 491 pg/mg and >322 pg/mg, respectively 24 .…”

Association of Urinary Dickkopf-3 with Residual Renal Function Decline in Patients Undergoing Peritoneal Dialysis

“…Urinary DKK-3 is a novel biomarker of acute kidney injury and CKD [ 14 , 15 , 19 ]. In particular, in non-dialytic CKD patients, urinary DKK-3 levels have been associated with CKD progression regardless of disease etiology [ 14 ].…”

Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease

“…DKK-3, a member of the glycoprotein family (DKK1-4) (Gröne et al, 2017), is a recently discovered stress-induced tubular-derived renal biomarker for interstitial fibrosis (Federico et al, 2016;Fang et al, 2020;Seibert et al, 2021). It mainly promotes renal tubular epithelial cells producing fibrogenic molecules secreted by stress stimulation (Schunk et al, 2021a).…”

“…It mainly promotes renal tubular epithelial cells producing fibrogenic molecules secreted by stress stimulation (Schunk et al, 2021a). Expression of DKK-3 in the developing kidney would cease after kidney maturation and would reignite when the kidney tissue is damaged (Seibert et al, 2021). Lipphardt et al (2019) have found that DKK3 could significantly reduce the area percentage, total length, and bifurcation number of capillary structures in renal microvascular endothelial cells.…”