Chronic kidney disease is a progressive condition that can significantly impact life expectancy and quality of life, particularly in children. According to a study published in The Lancet, researchers have discovered that urinary Dickkopf-related protein 3 (DKK3), a kidney tubular cell stress marker, can be used to identify the short-term risk of chronic kidney disease progression in children.
This can aid in determining those who will benefit from specific nephroprotective interventions. Chronic kidney disease that begins in childhood is a progressive condition that can significantly affect life expectancy and quality of life.
The study was conducted as an observational cohort study, where the researchers examined the association between urinary DKK3 and the combined kidney endpoint (i.e., the composite of 50% reduction of the estimated glomerular filtration rate [eGFR] or progression to end-stage kidney disease) or the risk of kidney replacement therapy (i.e., dialysis or transplantation). They also assessed the interaction of the combined kidney endpoint with intensified blood pressure reduction in the randomized controlled ESCAPE trial.
The cohort comprised 659 children aged 3-18 with chronic kidney disease from the prospective multicentre ESCAPE and 4C studies. Urinary DKK3 and eGFR were measured at baseline, and 6-monthly follow-up visits and analyses were adjusted for confounding factors such as age, sex, hypertension, systolic blood pressure SD score (SDS), BMI SDS, albuminuria, and eGFR.
In both cohorts, the results showed that urinary DKK3 levels above the median (>1689 pg/mg creatinine) were significantly associated with a more significant 6-month eGFR decline than with urinary DKK3 levels at or below the median. This was independent of diagnosis, eGFR, and albuminuria.
In the ESCAPE study, intensified blood pressure control had a beneficial effect limited to children with urinary DKK3 higher than 1689 pg/mg creatinine in terms of the combined kidney endpoint and the need for kidney replacement therapy. In the 4C study, inhibition of the renin–angiotensin–aldosterone system resulted in significantly lower urinary DKK3 concentrations.
These findings suggest that urinary DKK3 levels can indicate the short-term risk of declining kidney function in children with chronic kidney disease and enable personalized medicine approaches by identifying those who would benefit from pharmacological nephroprotection, such as intensified blood pressure lowering.
This study highlights the potential of urinary DKK3 as a biomarker for monitoring kidney disease progression and guiding treatment decisions in children with chronic kidney disease. The implications of these results are significant for the management of childhood-onset chronic kidney disease, a complex condition that requires ongoing monitoring and treatment.
By identifying those who are at the most significant risk of disease progression, healthcare professionals can implement interventions to slow the decline in kidney function and improve outcomes for these patients. This study underscores the importance of biomarker research in nephrology and highlights the potential of urinary DKK3 as a valuable tool for clinical decision-making in pediatric kidney disease.
