Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study

Pediatr Nephrol. 2023 Aug;38(8):2851-2860. doi: 10.1007/s00467-023-05886-1. Epub 2023 Feb 15.

Abstract

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.

Keywords: Biomarker; CKD; CKD progression; Cardiac surgery; Congenital heart disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury* / complications
  • Biomarkers
  • Cardiac Surgical Procedures* / adverse effects
  • Child
  • Glomerular Filtration Rate
  • Heart Defects, Congenital* / complications
  • Heart Defects, Congenital* / surgery
  • Humans
  • Interleukin-18
  • Renal Insufficiency, Chronic* / complications
  • Uromodulin

Substances

  • Interleukin-18
  • Uromodulin
  • Biomarkers