Date of Award

January 2022

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jason H. Greenberg

Abstract

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.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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