Soluble IL-33 receptor predicts survival in acute kidney injury

Authors

  • Stefan Erfurt Department of Internal Medicine I – Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel - Germany https://orcid.org/0000-0001-8892-1805
  • Meike Hoffmeister Institute of Biochemistry, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel and Faculty of Health Sciences (FGW), joint faculty of the University of Potsdam, the Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus - Germany https://orcid.org/0000-0003-3561-5286
  • Stefanie Oess Institute of Biochemistry, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel and Faculty of Health Sciences (FGW), joint faculty of the University of Potsdam, the Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus - Germany
  • Katharina Asmus Department of Internal Medicine I – Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel - Germany
  • Susann Patschan Department of Internal Medicine I – Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel and Faculty of Health Sciences (FGW), joint faculty of the University of Potsdam, the Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus - Germany
  • Oliver Ritter Department of Internal Medicine I – Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel and Faculty of Health Sciences (FGW), joint faculty of the University of Potsdam, the Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus - Germany
  • Daniel Patschan Department of Internal Medicine I – Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel and Faculty of Health Sciences (FGW), joint faculty of the University of Potsdam, the Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus - Germany https://orcid.org/0000-0002-6914-5254

DOI:

https://doi.org/10.33393/jcb.2022.2386

Keywords:

Acute kidney injury, IL-33, Soluble ST2, Mortality, Biomarker

Abstract

Introduction: The prediction of acute kidney injury (AKI)-related outcomes remains challenging. Herein we prospectively quantified soluble ST2 (sST2), the circulating isoform of the IL-33 receptor, in hospitalized patients with AKI.

Methods: In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University hospital. sST2 was measured within a maximum of 48 hours from the time of diagnosis of AKI. The following endpoints were defined: in-hospital death, dialysis, recovery of kidney function until demission.

Results: In total, 151 individuals were included in the study. The in-hospital mortality was 16.6%, dialysis therapy became mandatory in 39.7%, no recovery of kidney function occurred in 27.8%. sST2 was significantly higher in nonsurvivors (p = 0.024) but did not differ in the two other endpoints. The level of sST2 increased significantly with the severity of AKI. Further differences were detected in subjects with heart insufficiency (lower sST2), and in patients that required ICU treatment, or ventilatory therapy, or vasopressors (all higher).

Conclusions: The current study suggests sST2 as biomarker of “acute distress”: it predicts post-AKI survival and substantially increases in subjects with a higher degree of cumulative morbidity under acute circumstances (e.g., ICU therapy, vasopressor administration).

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References

Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14(10):607-625. https://doi.org/10.1038/s41581-018-0052-0 PMID:30135570

Selby NM, Crowley L, Fluck RJ, et al. Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients. Clin J Am Soc Nephrol. 2012;7(4):533-540. https://doi.org/10.2215/cjn.08970911 PMID: 22362062

Uchino S, Bellomo R, Bagshaw SM, Goldsmith D. Transient azotaemia is associated with a high risk of death in hospitalized patients. Nephrol Dial Transplant. 2010;25(6):1833-1839. https://doi.org/10.1093/ndt/gfp624 PMID: 20054022

Melo FAF, Macedo E, Fonseca Bezerra AC, et al. A systematic review and meta-analysis of acute kidney injury in the intensive care units of developed and developing countries. PLoS One. 2020;15(1):e0226325. https://doi.org/10.1371/journal.pone.0226325 PMID:31951618

Fields JK, Günther S, Sundberg EJ. Structural basis of IL-1 family cytokine signaling. Front Immunol. 2019;10:1412. https://doi.org/10.3389/fimmu.2019.01412 PMID:31281320

Pichery M, Mirey E, Mercier P, et al. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J Immunol. 2012;188(7):3488-3495. https://doi.org/10.4049/jimmunol.1101977. PMID: 22371395.

Roussel L, Erard M, Cayrol C, Girard J-P. Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket. EMBO Rep. 2008;9(10):1006-1012. https://doi.org/10.1038/embor.2008.145 PMID:18688256

Kotsiou OS, Gourgoulianis KI, Zarogiannis SG. IL-33/ST2 axis in organ fibrosis. Front Immunol. 2018;9:2432. https://doi.org/10.3389/fimmu.2018.02432 PMID:30405626

Cayrol C, Girard J-P. Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev. 2018;281(1):154-168. https://doi.org/10.1111/imr.12619 PMID:29247993

Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury – pathophysiological basis and clinical performance. Acta Physiol (Oxf). 2017;219(3):554-572. https://doi.org/10.1111/apha.12764 PMID: 27474473

Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021;7(1):52. https://doi.org/10.1038/s41572-021-00284-z PMID: 34267223

Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013;61(5):649-672. https://doi.org/10.1053/j.ajkd.2013.02.349 PMID:23499048

Akcay A, Nguyen Q, He Z, et al. IL-33 exacerbates acute kidney injury. J Am Soc Nephrol. 2011;22(11):2057-2067. https://doi.org/10.1681/ASN.2010091011 PMID:21949094

Ferhat M, Robin A, Giraud S, et al. Endogenous IL-33 contributes to kidney ischemia-reperfusion injury as an alarmin. J Am Soc Nephrol. 2018;29(4):1272-1288. https://doi.org/10.1681/ASN.2017060650 PMID:29436517

Chen Z, Hu Q, Huo Y, Zhang R, Fu Q, Qin X. Serum interleukin-33 is a novel predictive biomarker of hemorrhage transformation and outcome in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2021;30(2):105506. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105506PMID:33307292

Firouzabadi N, Dashti M, Dehshahri A, Bahramali E. Biomarkers of IL-33 and sST2 and lack of association with carvedilol therapy in heart failure. Clin Pharmacol. 2020;12:53-58. https://doi.org/10.2147/CPAA.S256290 PMID:32607003

Behairy OG, Elsadek AE, Behiry EG, Elhenawy IA, Shalan NH, Sayied KR. Clinical value of serum interleukin-33 biomarker in infants with neonatal cholestasis. J Pediatr Gastroenterol Nutr. 2020;70(3):344-349. https://doi.org/10.1097/MPG.0000000000002565 PMID:31764415

Erfurt S, Hoffmeister M, Oess S, et al. Serum IL-33 as a biomarker in different diseases: useful parameter or much need for clarification? J Circ Biomark. 2021;10:20-25. https://doi.org/10.33393/jcb.2021.2327 PMID:34858526

Ketelaar ME, Nawijn MC, Shaw DE, Koppelman GH, Sayers I. The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma. Clin Exp Allergy. 2016;46(6):884-887. https://doi.org/10.1111/cea.12718 PMID:26850082

Asaka D, Yoshikawa M, Nakayama T, Yoshimura T, Moriyama H, Otori N. Elevated levels of interleukin-33 in the nasal secretions of patients with allergic rhinitis. Int Arch Allergy Immunol. 2012;158(s1)(suppl 1):47-50. https://doi.org/10.1159/000337764 PMID:22627366

Vyshnevska I, Kopytsya M, Hilоva Y, Protsenko E, Petyunina O. Biomarker SST2 as an early predictor of acute renal injury in patients with ST-segment elevation acute myocardial infarction. Georgian Med News. 2020;(302):53-58. PMID:32672690

Lobdell KW, Parker DM, Likosky DS, et al. Preoperative serum ST2 level predicts acute kidney injury after adult cardiac surgery. J Thorac Cardiovasc Surg. 2018;156(3):1114-1123.e2. https://doi.org/10.1016/j.jtcvs.2018.03.149 PMID:29759735

Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Karger Publishers; 2012. https://doi.org/10.1159/000339789

Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-810. https://doi.org/10.1001/jama.2016.0287 PMID: 26903338

Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52(19):1527-1539. https://doi.org/10.1016/j.jacc.2008.07.051 PMID: 19007588

Arroyo V, Ginès P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23(1):164-176. https://doi.org/10.1002/hep.510230122 PMID:8550036

Fiorentino M, Tohme FA, Wang S, Murugan R, Angus DC, Kellum JA. Long-term survival in patients with septic acute kidney injury is strongly influenced by renal recovery. PLoS One. 2018;13(6):e0198269. https://doi.org/10.1371/journal.pone.0198269 PMID:29870535

Bagshaw SM, George C, Bellomo R; ANZICS Database Management Committe. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant. 2008;23(5):1569-1574. https://doi.org/10.1093/ndt/gfn009PMID:18281319

Hall IE, Coca SG, Perazella MA, et al. Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis. Clin J Am Soc Nephrol. 2011;6(12):2740-2749. https://doi.org/10.2215/cjn.04960511 PMID: 22034509

Singer E, Elger A, Elitok S, et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int. 2011;80(4):405-414. https://doi.org/10.1038/ki.2011.41 PMID:21412214

Nickolas TL, Schmidt-Ott KM, Canetta P, et al. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J Am Coll Cardiol. 2012 Jan 17;59(3):246-255. https://doi.org/10.1016/j.jacc.2011.10.854 PMID: 22240130

Sánchez-Más J, Lax A, Asensio-López MC, et al. Modulation of IL-33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers. Eur J Clin Invest. 2014;44(7):643-651. https://doi.org/10.1111/eci.12282 PMID:24837094

Tung YC, Chang CH, Chen YC, Chu PH. Combined biomarker analysis for risk of acute kidney injury in patients with ST-segment elevation myocardial infarction. PLoS One. 2015;10(4):e0125282. https://doi.org/10.1371/journal.pone.0125282 PMID: 25853556

Koyner JL, Garg AX, Coca SG, et al; TRIBE-AKI Consortium. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol. 2012;23(5):905-914. https://doi.org/10.1681/ASN.2011090907 PMID:22383693

Caironi P, Latini R, Struck J, et al; ALBIOS Study Investigators. Circulating proenkephalin, acute kidney injury, and its improvement in patients with severe sepsis or shock. Clin Chem. 2018;64(9):1361-1369. https://doi.org/10.1373/clinchem.2018.288068 PMID:30012641

Hollinger A, Wittebole X, François B, et al. Proenkephalin A 119-159 (Penkid) is an early biomarker of septic acute kidney injury: the Kidney in Sepsis and Septic Shock (Kid-SSS) Study. Kidney Int Rep. 2018;3(6):1424-1433. https://doi.org/10.1016/j.ekir.2018.08.006PMID:30450469

Schunk SJ, Zarbock A, Meersch M, et al. Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study. Lancet. 2019;394(10197):488-496. https://doi.org/10.1016/s0140-6736(19)30769-x PMID: 31202596

Fang X, Hu J, Chen Y, Shen W, Ke B. Dickkopf-3: current knowledge in kidney diseases. Front Physiol. 2020;11:533344. https://doi.org/10.3389/fphys.2020.533344 PMID:33391006

Hoste E, Bihorac A, Al-Khafaji A, et al; RUBY Investigators. Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study. Intensive Care Med. 2020;46(5):943-953. https://doi.org/10.1007/s00134-019-05919-0 PMID:32025755

Ostermann M, Zarbock A, Goldstein S, et al. Recommendations on acute kidney injury biomarkers from the acute disease quality initiative consensus conference: a consensus statement. JAMA Netw Open. 2020;3(10):e2019209. https://doi.org/10.1001/jamanetworkopen.2020.19209 PMID: 33021646

Hur M, Kim H, Kim HJ, et al; GREAT Network. Soluble ST2 has a prognostic role in patients with suspected sepsis. Ann Lab Med. 2015;35(6):570-577. https://doi.org/10.3343/alm.2015.35.6.570 PMID:26354344

Hoogerwerf JJ, Tanck MWT, van Zoelen MAD, Wittebole X, Laterre P-F, van der Poll T. Soluble ST2 plasma concentrations predict mortality in severe sepsis. Intensive Care Med. 2010;36(4):630-637. https://doi.org/10.1007/s00134-010-1773-0 PMID:20151106

Published

2022-06-06

How to Cite

Erfurt, S., Hoffmeister, M., Oess, S., Asmus, K., Patschan, S., Ritter, O., & Patschan, D. (2022). Soluble IL-33 receptor predicts survival in acute kidney injury. Journal of Circulating Biomarkers, 11(1), 28–35. https://doi.org/10.33393/jcb.2022.2386

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Section

Original research article
Received 2022-02-17
Accepted 2022-05-16
Published 2022-06-06

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