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Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study
Christina de Fontnouvelle1, Michael Zappitelli2, Heather R Thiessen-Philbrook3
1Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA.
Insights
Children undergoing cardiac surgery face higher risks of chronic kidney disease (CKD). Urine biomarkers like uromodulin and IL-18 measured post-surgery may help predict estimated glomerular filtration rate (eGFR) decline in pediatric patients.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Surgery
- Biomarker Discovery
Background:
- Congenital heart disease (CHD) surgery in children increases long-term chronic kidney disease (CKD) risk.
- Early identification of children at risk for CKD post-surgery is crucial for timely intervention.
- Urinary biomarkers may offer insights into tubular health and injury, aiding prognostication of kidney function decline.
Purpose of the Study:
- To investigate the association between urinary biomarkers and the rate of estimated glomerular filtration rate (eGFR) decline in children post-cardiac surgery.
- To assess the role of cyanotic heart disease in long-term eGFR decline.
- To identify predictive markers for CKD development in pediatric cardiac surgery patients.
Main Methods:
- The ASSESS-AKI cohort enrolled 117 children (1 month to 18 years) undergoing cardiac surgery.
- Urinary biomarkers (uromodulin, NGAL, KIM-1, IL-18, L-FABP) were measured 3 months post-surgery.
- Mixed-effect models analyzed associations between biomarkers, cyanotic heart disease, and annual eGFR decline over 4 years.
Main Results:
- Children with cyanotic heart disease had lower median eGFR throughout follow-up but not a faster decline rate.
- Lower urinary uromodulin and IL-18 levels at 3 months post-surgery were associated with a faster monthly eGFR decline.
- After adjusting for clinical factors, lower uromodulin and IL-18 concentrations remained linked to eGFR decline (p=0.07 and p=0.04, respectively).
Conclusions:
- Reduced urinary uromodulin and IL-18 levels at 3 months post-cardiac surgery are associated with a faster decline in eGFR in children.
- These biomarkers may aid in predicting long-term kidney function in pediatric patients after heart surgery.
- While cyanotic heart disease impacts baseline eGFR, it did not correlate with accelerated eGFR decline in this cohort.
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. A higher-resolution version of the Graphical abstract is available as Supplementary information.
