Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children

Rationale & Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. Study Design: Prospective longitudinal cohort study. Setting & Participants: 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Exposure: Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. Outcome: CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). Analytic Approach: Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. Results: Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P < 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P = 0.008). Plasma suPAR levels showed little change over 6 months. Limitations: Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. Conclusions: Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.