Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates

Rationale & Objective: Children born before 28 weeks' gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular fi ltration rate (eGFR) over time. Study Design: A cohort study of neonates with an exploratory case -control study of a subset of the cohort. Setting & Participants: 327 neonates born at 24-27 weeks' gestation with 2 -year eGFR data from the PENUT (Preterm Erythropoietin Neuroprotection Trial) and the REPaIReD (Recombinant Erythropoietin for Prevention of Infant Renal Disease) study. Exposures: 11 urinary biomarkers measured at 27, 30, and 34 weeks' postmenstrual age for the primary cohort study and 10 additional biomarkers for the exploratory case -control study. Outcomes: eGFR < 90 mL/min/1.73 m(2) at 2 years corrected for GA. Analytical Approach: Linear mixed models to assess differences in biomarker values between neonates in whom CKD did and did not develop, accounting for multiple comparisons using Bonferroni-Holm correction in the cohort study only. Cohort analyses were adjusted for sex, GA, and body mass index. Cases were matched to controls on these variables in the casecontrol study. Results: After adjusting for weeks of GA, urinary levels of alpha- glut athione-S-transferase (log difference, 0.27; 95% CI, 0.12-0.43), albumin (log difference, 0.13; 95% CI, 0.02-0.25), and cysatin C (log difference, 0.19; 95% CI, 0.04-0.3 4) were higher in those in whom CKD developed than in those in whom it did not. Urinary albumin and cystatin C levels did not remain signi fi cantly different after Bonferroni-Holm correction. In the exploratory case -control analysis, there were no differences in any biomarkers between cases and controls. Limitations: Early deaths and a high number of subjects without eGFR at 2 years corrected for GA. Conclusions: Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for CKD. Additional studies are needed to con fi rm these fi ndings. Funding: Grants from government (National Institutes of Health).