CKD screening: urinary albumin or uDKK3 or both?

Abstract

Approximately 750 million people worldwide suffer from chronic kidney diseases (CKD)—a leading cause of cardiovascular morbidity and premature mortality—but early identification of progressive kidney function decline in patients at risk is still a challenge. CKD diagnosis relies on estimated glomerular filtration rate (eGFR) and albuminuria screening, primarily reflecting glomerular injury. Nevertheless, in a substantial proportion of affected subjects progressive CKD initially remains undetected, since kidney function deteriorates through ongoing tubulointerstitial injury without significant albuminuria, a condition known as ‘non-albuminuric’ CKD.

Urinary Dickkopf-3 (uDKK3) has emerged as an innovative biomarker of progressive CKD, which is expressed by proximal tubular epithelial cells as a response to continuing injury. It is secreted into the urine, where it signals ongoing fibrogenic activity within the kidney. Clinical studies across a broad range of CKD etiologies—in adults and children alike—have shown that elevated uDKK3 significantly improved detection and prediction of progressive CKD after adjustment for established CKD risk markers including albuminuria. Moreover, in primarily non-albuminuric populations, e.g. those with type 2 diabetes and patients with heart or lung diseases, uDKK3 identifies high-risk individuals for future decline of kidney function.

These findings support the hypothesis that CKD progression follows different pathways of mainly glomerular or tubulointerstitial injury. It is therefore plausible to use complementary biomarkers for CKD screening—albuminuria and uDKK3–each reflecting a distinct biological dimension of kidney injury. We discuss the limitations of albuminuria screening and propose a framework for integrating tubular markers like uDKK3 into future CKD screening strategies.