CKD screening: urinary albumin or uDKK3 or both?

Area of Science:

• Nephrology
• Biomarker Discovery
• Chronic Kidney Disease Pathophysiology

Background:

• Chronic kidney diseases (CKD) impact 750 million globally, leading to significant morbidity and mortality.
• Current CKD diagnosis using estimated glomerular filtration rate (eGFR) and albuminuria primarily detects glomerular injury, often missing progressive tubulointerstitial damage.
• Non-albuminuric CKD, driven by tubulointerstitial injury, presents a diagnostic challenge for early identification of kidney function decline.

Purpose of the Study:

• To evaluate urinary Dickkopf-3 (uDKK3) as a novel biomarker for detecting and predicting progressive CKD.
• To assess the utility of uDKK3 in identifying high-risk individuals, particularly those with non-albuminuric CKD.
• To propose integrating uDKK3 with albuminuria for comprehensive CKD screening.

Main Methods:

• Clinical studies involving diverse CKD etiologies in adult and pediatric populations.
• Analysis of urinary Dickkopf-3 (uDKK3) levels as a marker of proximal tubular epithelial cell injury.
• Statistical adjustment for established CKD risk markers, including albuminuria, to determine uDKK3's predictive value.

Main Results:

• Elevated uDKK3 levels significantly improved the detection and prediction of progressive CKD across various etiologies.
• uDKK3 identified high-risk individuals for kidney function decline in non-albuminuric populations, including those with type 2 diabetes, heart, and lung diseases.
• Findings support distinct CKD progression pathways involving glomerular versus tubulointerstitial injury.

Conclusions:

• Urinary Dickkopf-3 (uDKK3) is a promising biomarker for progressive CKD, complementing albuminuria screening.
• Integrating uDKK3 into screening strategies can enhance early detection of kidney damage, particularly in non-albuminuric forms.
• Complementary biomarkers reflecting distinct injury pathways are crucial for effective CKD management.