TY - JOUR
T1 - Biomarkers of eGFR decline after cardiac surgery in children
T2 - findings from the ASSESS-AKI study
AU - de Fontnouvelle, Christina
AU - Zappitelli, Michael
AU - Thiessen-Philbrook, Heather R.
AU - Jia, Yaqi
AU - Kimmel, Paul L.
AU - Kaufman, James S.
AU - Devarajan, Prasad
AU - Parikh, Chirag R.
AU - Greenberg, Jason H.
N1 - Funding Information:
This research is supported by the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium (grant No. U01DK082185). Dr. Greenberg is supported by NIH career development grant K08DK110536. Dr. Parikh is supported by the NIH (grant No. R01HL085757) to fund the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury Consortium to study novel biomarkers of acute kidney injury in cardiac surgery.
Funding Information:
The opinions expressed in this article are the authors’ own and do not necessarily reflect the views of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the Department of Health and Human Services, or the US Government.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to International Pediatric Nephrology Association.
PY - 2023/8
Y1 - 2023/8
N2 - Background: Children who require surgery for congenital heart disease have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of tubular health and injury may help improve the prognostication of estimated glomerular filtration rate (eGFR) decline. Methods: We enrolled children from 1 month to 18 years old undergoing cardiac surgery in the ASSESS-AKI cohort. We used mixed-effect models to assess the association between urinary biomarkers (log2-transformed uromodulin, NGAL, KIM-1, IL-18, L-FABP) measured 3 months after cardiac surgery and cyanotic heart disease with the rate of eGFR decline at annual in-person visits over 4 years. Results: Of the 117 children enrolled, 30 (24%) had cyanotic heart disease. During 48 months of follow-up, the median eGFR in the subgroup of children with cyanotic heart disease was lower at all study visits as compared with children with acyanotic heart disease (p = 0.01). In the overall cohort, lower levels of both urine uromodulin and IL-18 after discharge were associated with eGFR decline. After adjustment for age, RACHS-1 surgical complexity score, proteinuria, and eGFR at the 3-month study visit, lower concentrations of urine uromodulin and IL-18 were associated with a monthly decline in eGFR (uromodulin β = 0.04 (95% CI: 0.00–0.09; p = 0.07) IL-18 β = 0.07 (95% CI: 0.01–0.13; p = 0.04), ml/min/1.73 m2 per month). Conclusions: At 3 months after cardiac surgery, children with lower urine uromodulin and IL-18 concentrations experienced a significantly faster decline in eGFR. Children with cyanotic heart disease had a lower median eGFR at all time points but did not experience faster eGFR decline. Graphical abstract: [Figure not available: see fulltext.]
AB - Background: Children who require surgery for congenital heart disease have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of tubular health and injury may help improve the prognostication of estimated glomerular filtration rate (eGFR) decline. Methods: We enrolled children from 1 month to 18 years old undergoing cardiac surgery in the ASSESS-AKI cohort. We used mixed-effect models to assess the association between urinary biomarkers (log2-transformed uromodulin, NGAL, KIM-1, IL-18, L-FABP) measured 3 months after cardiac surgery and cyanotic heart disease with the rate of eGFR decline at annual in-person visits over 4 years. Results: Of the 117 children enrolled, 30 (24%) had cyanotic heart disease. During 48 months of follow-up, the median eGFR in the subgroup of children with cyanotic heart disease was lower at all study visits as compared with children with acyanotic heart disease (p = 0.01). In the overall cohort, lower levels of both urine uromodulin and IL-18 after discharge were associated with eGFR decline. After adjustment for age, RACHS-1 surgical complexity score, proteinuria, and eGFR at the 3-month study visit, lower concentrations of urine uromodulin and IL-18 were associated with a monthly decline in eGFR (uromodulin β = 0.04 (95% CI: 0.00–0.09; p = 0.07) IL-18 β = 0.07 (95% CI: 0.01–0.13; p = 0.04), ml/min/1.73 m2 per month). Conclusions: At 3 months after cardiac surgery, children with lower urine uromodulin and IL-18 concentrations experienced a significantly faster decline in eGFR. Children with cyanotic heart disease had a lower median eGFR at all time points but did not experience faster eGFR decline. Graphical abstract: [Figure not available: see fulltext.]
KW - Biomarker
KW - CKD
KW - CKD progression
KW - Cardiac surgery
KW - Congenital heart disease
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U2 - 10.1007/s00467-023-05886-1
DO - 10.1007/s00467-023-05886-1
M3 - Article
C2 - 36790467
AN - SCOPUS:85148073469
SN - 0931-041X
VL - 38
SP - 2851
EP - 2860
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 8
ER -