Date of Award
Medical Doctor (MD)
Jason H. Greenberg
Background: It has been previously demonstrated that children who require surgery for congenital heart disease (CHD) have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of ongoing kidney injury, inflammation, and fibrosis may help improve prognostication of estimated GFR (eGFR) decline.
Methods: Children from 1 month to 18 years old undergoing cardiac surgery were enrolled in the ASSESS-AKI Cohort. Mixed effects models were used in a retrospective analysis to assess the association between clinical biomarkers (age, sex, cyanotic heart disease) and urinary biomarkers (log2-transformed NGAL, KIM-1, IL-18, L-FABP, uromodulin, microalbumin) measured 3 months after cardiac surgery with the rate of eGFR decline at in-person visits over 4 years. All urine biomarkers were indexed to urine creatinine.
Results: Data from 117 children undergoing cardiac surgery were collected, 28 (24%) of whom had cyanotic heart disease. During 48 months of follow-up the median eGFR decline was 6.4 ml/min/1.73m2 in the overall cohort and 12.9 ml/min/1.73m2 in the subgroup of children with cyanotic heart disease. In the overall cohort, when modeled continuously (per log2), lower levels of both urine IL-18 and uromodulin after discharge were associated with eGFR decline. After adjustment for age, RACHS-1, proteinuria, and eGFR at the 3-month study visit, lower concentrations of both of these biomarkers were associated with a monthly decline in eGFR (IL-18 β=0.068 [95% CI: 0.0049, 0.13; p 0.035], uromodulin β=0.041 [95% CI: -0.0041, 0.087; p 0.074]). No other urine biomarkers were associated with eGFR decline.
Conclusions: At 3 months after cardiac surgery, children with lower IL-18 and uromodulin concentrations experienced significantly faster monthly decline in eGFR. Cyanotic heart disease was also a risk factor for faster GFR decline. Urine uromodulin and IL-18 may have prognostic value and help identify children at highest risk for eGFR decline.
De Fontnouvelle, Christina Anne-Josiane, "Biomarkers Of Egfr Decline After Pediatric Cardiac Surgery In The Assess-Aki Cohort" (2022). Yale Medicine Thesis Digital Library. 4063.