Urinary Biomarker Can Predict Renal Injury in CKD Patients After Cardiac Procedure

Several biomarkers of AKI have shown diagnostic and prognostic value. Urinary dickkopf-3 (DKK3) is a stress-induced, renal tubular epithelium-derived, secreted glycoprotein that induces tubulointerstitial fibrosis through the activation of the canonical Wnt/β-catenin signalling pathway. DKK3 has been identified as a biomarker predicting chronic kidney disease (CKD) progression. In this present study, Dr Giuseppina Roscigno PhD and her team conducted a study to assess the diagnostic usefulness of baseline uDKK3/uCr to predict CA-AKI and persistent kidney dysfunction after CM exposure; and compared baseline uDKK3/uCr with other proposed biomarkers, that is, sCyC, uNGAL, and sNGAL, in predicting the above outcomes.

In this observational study, the researchers included a total of 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. They assessed the urinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) in 458 patients. They determined CA-AKI as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration and Persistent kidney dysfunction as persistent estimated glomerular filtration rate reduction ≥25% at one month compared with baseline.

Key findings of the study were:

• Among 458 patients, the researchers identified CA-AKI in 64 patients (14%) and noted that baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction.
• They found that net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores.
• They also found similar findings for the integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores.
• They identified 57 patients with persistent kidney dysfunction (12%) and noted that baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction.
• They also noted that adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI.

The authors concluded, "Baseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction."

For further information:

Giuseppina Roscigno PhD et al., Urinary Dickkopf-3 and Contrast-Associated Kidney Damage, 2021-06-01, Volume 77, Issue 21, Pages 2667-2676.