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Pediatric Nephrology
Erschienen in: Pediatric Nephrology 2/2024

19.08.2023 | Original Article

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

verfasst von: Daniella Levy Erez, Shah Lokesh, Kathryn D. Howarth, Sherin Meloni, Lance Ballester, Benjamin Laskin, Kathleen E. Sullivan, Joshua Blinder

Erschienen in: Pediatric Nephrology | Ausgabe 2/2024

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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.

Graphical abstract

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Literatur
1.
Alten JA, Cooper DS, Blinder JJ, Selewski DT, Tabbutt S, Sasaki J, Gaies MG, Bertrandt RA, Smith AH, Reichle G, Gist KM, Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) Investigators (2021) Epidemiology of acute kidney injury after neonatal cardiac surgery: a report from the multicenter neonatal and pediatric heart and renal outcomes network. Crit Care Med 49:e941–e951CrossRefPubMed
2.
Grieshaber P, Moller S, Arneth B, Roth P, Niemann B, Renz H, Boening A (2020) Predicting cardiac surgery-associated acute kidney injury using a combination of clinical risk scores and urinary biomarkers. Thorac Cardiovasc Surg 68:389–400CrossRefPubMed
3.
Brown JR, Hisey WM, Marshall EJ, Likosky DS, Nichols EL, Everett AD, Pasquali SK, Jacobs ML, Jacobs JP, Parikh CR (2016) Acute kidney injury severity and long-term readmission and mortality after cardiac surgery. Ann Thorac Surg 102:1482–1489CrossRefPubMedPubMedCentral
4.
Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A (2011) Acute kidney injury: a relevant complication after cardiac surgery. Ann Thorac Surg 92:1539–1547CrossRefPubMed
5.
Kwiatkowski DM, Krawczeski CD (2017) Acute kidney injury and fluid overload in infants and children after cardiac surgery. Pediatr Nephrol 32:1509–1517CrossRefPubMed
6.
7.
Watkins SC, Williamson K, Davidson M, Donahue BS (2014) Long-term mortality associated with acute kidney injury in children following congenital cardiac surgery. Paediatr Anaesth 24:919–926CrossRefPubMed
8.
Blinder JJ, Asaro LA, Wypij D, Selewski DT, Agus MS, Gaies M, Ferguson MA (2017) Acute kidney injury after pediatric cardiac surgery: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial. Pediatr Crit Care Med 18:638–646CrossRefPubMedPubMedCentral
9.
Haase-Fielitz A, Haase M, Bellomo R, Calzavacca P, Spura A, Baraki H, Kutschka I, Albert C (2017) Perioperative hemodynamic instability and fluid overload are associated with increasing acute kidney injury severity and worse outcome after cardiac surgery. Blood Purif 43:298–308CrossRefPubMed
10.
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Critical Care 11:R31CrossRefPubMedPubMedCentral
11.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Quality Acute Dialysis, Initiative workgroup (2004) Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute dialysis quality initiative (ADQI) group. Crit Care 8:R204–R212
12.
Eleftheriadis T, Pissas G, Crespo M, Nikolaou E, Liakopoulos V, Stefanidis I (2021) A role for human renal tubular epithelial cells in direct allo-recognition by CD4+ T-cells and the effect of ischemia-reperfusion. Int J Mol Sci 22:1733CrossRefPubMedPubMedCentral
13.
Singbartl K, Formeck CL, Kellum JA (2019) Kidney-immune system crosstalk in AKI. Semin Nephrol 39:96–106CrossRefPubMed
14.
Lee S, Huen S, Nishio H, Lee HK, Choi BS, Ruhrberg C, Cantley LG (2011) Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol 22:317–326CrossRefPubMedPubMedCentral
15.
Petrovic-Djergovic D, Popovic M, Chittiprol S, Cortado H, Ransom RF, Partida-Sánchez S (2015) CXCL10 induces the recruitment of monocyte-derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis. Clin Exp Immunol 180:305–315CrossRefPubMedPubMedCentral
16.
Pagowska-Klimek I, Swierzko AS, Michalski M, Głowacka E, Szala-Poździej A, Sokołowska A, Moll M, Krajewski WR, Romak J, Cedzyński M (2016) Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery. Clin Exp Immunol 184:257–263CrossRefPubMedPubMedCentral
17.
Uyar IS, Onal S, Uysal A, Ozdemir U, Burma O, Bulut V (2014) Evaluation of systemic inflammatory response in cardiovascular surgery via interleukin-6, interleukin-8, and neopterin. Heart Surg Forum 17:E13–E17CrossRefPubMed
18.
19.
Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P (2008) Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 3:665–673CrossRefPubMedPubMedCentral
20.
Zheng J, Xiao Y, Yao Y, Xu G, Li C, Zhang Q, Li H, Han L (2013) Comparison of urinary biomarkers for early detection of acute kidney injury after cardiopulmonary bypass surgery in infants and young children. Pediatr Cardiol 34:880–886CrossRefPubMed
21.
Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Bagshaw SM, Haase-Fielitz A, Haase M, Ostland V, Noiri E, Westerman M (2015) Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass. Ren Fail 37:408–416CrossRefPubMed
22.
23.
Levy Erez D, Denburg MR, Afolayan S, Jodele S, Wallace G, Davies SM, Seif AE, Bunin N, Laskin BL, Sullivan KE (2020) Acute kidney injury in children after hematopoietic cell transplantation is associated with elevated urine CXCL10 and CXCL9. Biol Blood Marrow Transplant 26:1266–1272CrossRef
24.
Tokunaga R, Zhang W, Naseem M (2018) CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - a target for novel cancer therapy. Cancer Treat Rev 63:40–47CrossRefPubMed
25.
Xia JB, Liu GH, Chen ZY, Mao CZ, Zhou DC, Wu HY, Park KS, Zhao H, Kim SK, Cai DQ, Qi XF (2016) Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation. Cytokine 81:63–70CrossRefPubMed
26.
Lazzeri E, Romagnani P (2016) CXCR3-binding chemokines: novel multifunctional therapeutic targets. Curr Drug Targets Immune Endocr Metabol Disord 5:109–118CrossRef
27.
Lazzeri E, Rotondi M, Mazzinghi B, Lasagni L, Buonamano A, Rosati A, Pradella F, Fossombroni V, La Villa G, Gacci M, Bertoni E (2005) High CXCL10 expression in rejected kidneys and predictive role of pretransplant serum CXCL10 for acute rejection and chronic allograft nephropathy. Transplantation 79:1215–1220CrossRefPubMed
28.
Raza A, Firasat S, Khaliq S, Aziz T, Mubarak M, Naqvi SAA, Mehdi SQ, Rizvi SAUH, Abid A (2017) The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection. Inflamm Res 66:425–432CrossRefPubMed
29.
Troncoso MF, Ortiz-Quintero J, Garrido-Moreno V (2021) VCAM-1 as a predictor biomarker in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis 1867:166170CrossRefPubMed
30.
Gibbs P, Berkley LM, Bolton EM, Briggs JD, Bradley JA (1993) Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts. Transpl Immunol 1:109–113CrossRefPubMed
31.
Wuthrich RP (1992) Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis. Kidney Int 42:903–914CrossRefPubMed
32.
Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–e473CrossRefPubMed
33.
Pabst von Ohain J, Sarris G, Tobota Z, Maruszewski B, Vida VL, Hörer J (2021) Risk evaluation in adult congenital heart surgery: analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database risk models on data from the European Congenital Heart Surgeons Association Congenital Database. Eur J Cardiothorac Surg 60:1397–1404CrossRefPubMed
34.
Mah KE, Hao S, Sutherland SM et al (2018) Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery. Pediatr Nephrol 33:511–520CrossRefPubMed
35.
R Core Team (2013) R: a language and environment for statistical computing. R foundation for statistical computing, Vienna
36.
Gasparin AA, de Andrade NPB, Hax V, Palominos PE, Siebert M, Marx R, Schaefer PG, Veronese FV, Monticielo OA (2020) Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis. BMC Rheumatol 4:67CrossRefPubMedPubMedCentral
37.
Bonanni V, Antonangeli F, Santoni A, Bernardini G (2019) Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells. J Immunother Cancer 7:290CrossRefPubMedPubMedCentral
38.
Pease JE (2017) Designing small molecule CXCR3 antagonists. Expert Opin Drug Discov 12:159–168CrossRefPubMed
39.
Scrascia G, Rotunno C, Simone S, Montemurno E, Amorese L, De Palo M, Castellano G, Pertosa GB, Gesualdo L, Paparella D (2017) Acute kidney injury in high-risk cardiac surgery patients: roles of inflammation and coagulation. J Cardiovasc Med 18:359–365CrossRef
40.
Metadaten
Titel
Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury
verfasst von
Daniella Levy Erez
Shah Lokesh
Kathryn D. Howarth
Sherin Meloni
Lance Ballester
Benjamin Laskin
Kathleen E. Sullivan
Joshua Blinder
Publikationsdatum
19.08.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 2/2024
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-023-06051-4

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