Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study.
Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss.
This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed.
In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10-2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23-0·42, p<0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733-910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08-3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67-26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50-122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45-5·37) and persistent renal dysfunction (OR 3·82, 1·32-11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76-2·39 and persistent renal dysfunction OR 1·05, 0·12-9·45).
Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective.
No study funding.
Schunk SJ
，Zarbock A
，Meersch M
，Küllmar M
，Kellum JA
，Schmit D
，Wagner M
，Triem S
，Wagenpfeil S
，Gröne HJ
，Schäfers HJ
，Fliser D
，Speer T
，Zewinger S
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Prediction of contrast-induced acute kidney injury by early post-procedural analysis of urinary biomarkers and intra-renal Doppler flow indices in patients undergoing coronary angiography.
The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI).
This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally.
CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001).
Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions.
Wybraniec MT
，Chudek J
，Bożentowicz-Wikarek M
，Mizia-Stec K
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Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children.
Preoperative urinary dickkopf-3 (DKK3) is proposed as an early biomarker for the prediction of acute kidney injury (AKI) in patients undergoing cardiac surgery. We explored the clinical utility of urinary DKK3 for the early predictive value for AKI, sepsis-associated AKI (SA-AKI), and pediatric intensive care unit (PICU) mortality in critically ill children.
Urine samples were collected during the first 24 h after admission for measurement of DKK3. AKI diagnosis was based on serum creatinine and urine output using the KDIGO criteria. SA-AKI was defined as AKI that occurred in children who met the sepsis criteria in accordance with the surviving sepsis campaign international guidelines for children.
Of the 420 children, 73 developed AKI, including 24 with SA-AKI, and 30 died during the PICU stay. The urinary DKK3 level was significantly associated with AKI, SA-AKI, and PICU mortality, even after adjustment for confounders. The area under the receiver operating characteristic curve of urinary DKK3 for the discrimination of AKI, SA-AKI, and PICU mortality was 0.70, 0.80, and 0.78, respectively.
Urinary DKK3 was independently associated with an increased risk for AKI, SA-AKI, and PICU mortality and may be predictive of the aforementioned issues in critically ill children.
Urinary dickkopf-3 (DKK3) has been identified as a preoperative biomarker for the prediction of acute kidney injury (AKI) following cardiac surgery or coronary angiography in adult patients. However, little is known about the clinical utility of urinary DKK3 in pediatric cohorts. This study demonstrated that urinary DKK3 is capable of early predicting AKI and pediatric intensive care unit (PICU) mortality and discriminating sepsis-associated AKI (SA-AKI) from other types of AKI. Urinary DKK3 may be an early biomarker for predicting AKI, SA-AKI, and PICU mortality in critically ill children.
Hu J
，Zhou Y
，Huang H
，Kuai Y
，Chen J
，Bai Z
，Li X
，Li Y
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