Serum Dickkopf-3 and CC Motif Chemokine Ligand-2 as Biomarkers of Tubular Stress and Renal Inflammation in Beta-Thalassaemia: A Cross-Sectional Comparative Study

Abstract

Conventional renal indices creatinine, urea, and estimated glomerular filtration rate (eGFR) detect kidney dysfunction in beta-thalassaemia major (BTM), after substantial tubular and glomerular damage has already occurred. Dickkopf-3 (DKK3), a secreted glycoprotein released by stressed proximal tubular epithelial cells, and CC motif chemokine ligand-2 (CCL2/MCP-1), the principal monocyte chemoattractant in renal interstitial inflammation, have been proposed as earlier and more mechanistically informative alternatives. Building on our previous report of renal function, electrolyte, and haematological, this study evaluates serum DKK3 and CCL2 concentrations across four clinically stratified groups and assesses their diagnostic accuracy by receiver operating characteristic (ROC) analysis.
One hundred and eighty participants were allocated to: healthy controls (G1, n = 30), BTM with kidney injury (G2, n = 30), non-thalassaemic chronic kidney disease (G3, n = 30), and BTM without kidney injury (G4, n = 90). Both biomarkers differed significantly across groups (P < 0.0001). DKK3 peaked in G2 (45.73 ± 0.95 ng/mL), while CCL2 reached its maximum in G4 (419.52 ± 12.75 ng/mL), substantially exceeding levels in both kidney-injury groups. ROC analysis confirmed outstanding discriminatory performance: for the clinically critical G1 versus G4 comparison, CCL2 achieved an area under the curve (AUC) of 0.997 (sensitivity 0.99, specificity 1.00 at a cutoff of 73.00 ng/mL) and DKK3 an AUC of 0.984 (sensitivity 0.91, specificity 1.00). The marked CCL2 elevation in thalassaemia patients without measurable renal impairment indicates that subclinical tubulointerstitial inflammation precedes detectable filtration decline. DKK3 and CCL2 together offer a complementary early-warning biomarker panel for nephropathy risk stratification in BTM.