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. 2024 Feb;39(2):589-595.
doi: 10.1007/s00467-023-06051-4. Epub 2023 Aug 19.

Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury

Daniella Levy Erez  1   2   3 , Shah Lokesh  4 , Kathryn D Howarth  5 , Sherin Meloni  5 , Lance Ballester  6 , Benjamin Laskin  5   7 , Kathleen E Sullivan  7   8 , Joshua Blinder  9   10
Affiliations

Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury

Daniella Levy Erez et al. Pediatr Nephrol. 2024 Feb.

Abstract

Background: Acute kidney injury (AKI) occurs frequently after infant cardiac surgery and is associated with poor outcomes, including mortality and prolonged length of stay. AKI mechanisms are poorly understood, limiting therapeutic targets. Emerging data implicates dysregulated immune activation in post-cardiac surgery AKI development. We sought to identify immune-mediated AKI biomarkers after infant cardiopulmonary bypass (CPB)-assisted cardiac surgery.

Methods: A single-center prospective study of 126 infants less than 1 year old undergoing CPB-assisted surgery enrolled between 10/2017 and 6/2019. Urine samples were collected before CPB and at 6, 24, 48, and 72 h after surgery. Immune-mediated biomarkers were measured using commercial ELISA and Luminex™ multiplex kits. Based on subject age, neonatal KDIGO (< 1 month) or KDIGO criteria defined AKI. The Kruskal-Wallis rank test determined the relationship between urinary biomarker measurements and AKI.

Results: A total of 35 infants (27%) developed AKI. AKI subjects were younger, underwent more complex surgery, and had longer CPB time. Subjects with AKI vs. those without AKI had higher median urinary chemokine 10 (C-X-C motif) ligand levels at 24, 48, and 72 h, respectively: 14.3 pg/ml vs. 5.3 pg/ml, 3.4 pg/ml vs. 0.8 pg/ml, and 1.15 pg/ml vs. 0.22 pg/ml (p < 0.05) post-CPB. At 6 h post-CPB, median vascular cell adhesion protein 1 (VCAM) levels (pg/mL) were higher among AKI subjects (491 pg/ml vs. 0 pg/ml, p = 0.04).

Conclusions: Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Acute kidney injury (AKI); Cardiac bypass surgery urinary biomarkers; Infant.

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Conflict of interest statement

Statements and declarations:

Disclosures: The authors have no conflict of interest to disclose.

Figures

Figure 1:
Figure 1:
Urinary VCAM-1 levels after cardiac bypass surgery among infants who developed AKI and those who did not develop AKI Figure 1 presents the urinary levels of VCAM-1 among the two groups (Green- AKI vs Red- No AKI) over the 72 hours. Central line presented as median with shaded color interquartile range. Levels at the 6-hour time point were significantly elevated among the AKI group compared with the non-AKI group. Y-Axis is represented on a log base 10 scale and 0 values were excluded.
Figure 2:
Figure 2:
Urinary CXCL10 levels after cardiac bypass surgery among infants who developed AKI and those who didn’t develop AKI Figure 2 presents the urinary levels of CXCL10 among the two groups (Green- AKI vs Red- No AKI) over the 72 hours. Central line presented as median with shaded color interquartile range. Levels increased over time among the AKI group compared with control with a statistical significance at the 24 hours 48- and 72-hour time points. Y-Axis is represented on a log base 10 scale and 0 values were excluded.
Figure 3 :
Figure 3 :
A schematic for VCAM-1 and CXCL10 in AKI pathway A framework of timeline of urinary biomarker presence in AKI
See this image and copyright information in PMC

References

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