Early Predictive Value of Matrix Metalloproteinase -9 and Tissue inhibitor of Metalloproteinase-1 for Acute Kidney Injury in Burn Patients: A Cohort Study
DOI:
https://doi.org/10.32007/jfacmedbaghdad3272Keywords:
Acute kidney injury, Biomarkers, Burns, Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinase-1Abstract
Background: Acute kidney injury is a serious complication of burn injuries. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 regulate extracellular matrix remodeling, and their dysregulation may contribute to the development of acute kidney injury.
Objectives: The study aimed to evaluate the early predictive value of serum matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 for acute kidney injury development in burn patients.
Methods: This cohort study was conducted at the Department of Biochemistry, College of Medicine, University of Baghdad, in collaboration with the Burns Specialized Hospital, Medical City Complex, Baghdad, from January to May 2025. Eighty-eight burn patients aged 17–67 years were enrolled. Venous blood was collected from each patient upon admission and 48 hours post burn for serum creatinine measurement. AKI was diagnosed and staged according to serum creatinine based criteria. Serum samples were separated and stored at −20°C until analysis. The serum concentrations of Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1. Statistical analyses included descriptive measures, tests for group comparisons, and ROC curve analysis to assess the diagnostic accuracy of Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 for acute kidney injury prediction.
Results: Serum MMP-9 and TIMP-1 levels were significantly elevated 48 hours post burn compared to the admission values, whereas creatinine levels showed no significant change. At 48 hours post burn, patients who developed AKI exhibited significantly higher MMP-9, TIMP-1, creatinine levels and total body surface area (TBSA) than those without AKI, while age did not differ significantly.
Conclusions: Elevated serum levels of MMP-9 and TIMP-1 within the first 48 hours following burn injury may serve as useful predictive biomarkers for the early development of acute kidney injury in patients with burns.
Received: 30 Jan. 2026, Revised:01 June 2026, Accepted: 07 Jul. 2026, Published Online: July 2026
References
1. Ostermann M, Lumlertgul N, Jeong R, et al. Acute kidney injury. The Lancet. 2025 Jan 18; 405(10474):241-56. https://doi.org/10.1016/S0140-6736(24)02385-7.
2. Wolosowicz M, Prokopiuk S, Kaminski TW. Matrix Metalloproteinase-9 (MMP-9) as a Therapeutic Target: Insights into Molecular Pathways and Clinical Applications. Pharmaceutics. 2025 Nov 4;17(11):1425. https://doi.org/10.3390/pharmaceutics17111425.
3. Zakiyanov O, Kalousová M, Zima T, et al. Matrix metalloproteinases in renal diseases: a critical appraisal. Kidney Blood Press Res. 2019 Jun 24;44(3):298-330. https://doi.org/10.1159/000499876.
4. Mulder PP, Vlig M, Boekema BK, et al. Persistent systemic inflammation in patients with severe burn injury is accompanied by influx of immature neutrophils and shifts in T cell subsets and cytokine profiles. Frontiers in immunology. 2021 Jan 29; 11:621222. https://doi.org/10.3389/fimmu.2020.621222.
5. Alberti G, Russo E, Lo Iacono M, et al. Matrix Metalloproteinases in Ureteropelvic Junction Obstruction: Their Role in Pathogenesis and Their Use as Clinical Markers. Cells. 2025 Mar 31;14(7):520. https://doi.org/10.3390/cells14070520.
6. Boutin L, Bellas Z, Walter T, et al. Kidney failure trajectories and sub phenotypes in severe burn patients. Anaesth. Crit. Care Pain Med. 2026 Jul 1;45(4):101696. https://doi.org/10.1016/j.accpm.2025.101696.
7. Legrand M, Clark AT, Neyra JA, et al. Acute kidney injury in patients with burns. Nature Reviews Nephrology. 2024 Mar; 20(3):188-200. https://doi.org/10.1038/s41581-023-00769-y.
8. Heng X, Li H. Timing of Renal Replacement Therapy in Burn Patients With Acute Kidney Injury: A Retrospective Cohort Study. Annals of Plastic Surgery. 2025 May;94(5):528-35. https://doi.org/10.1097/SAP.0000000000004178.
9. Lee N, Bae Y, Jang S, et al. Global, Regional, and National Burden of Burn Injury by Total Body Surface Area (TBSA) Involvement from 1990 to 2021, with Projections of Prevalence to 2050. Healthcare. 2025; 13(16): 2077. https://doi.org/10.3390/healthcare13162077.
10. Huang R, Yao Y, Xie S, et al. Optimal timing and approaches for first tangential excision in patients with≥ 70% TBSA burns: insights from a retrospective cohort of a mass casualty incident. Annals of Surgery. 2025 Jan 13:10-97. https://doi.org/10.1097/SLA.0000000000006626.
11. Yu G, Li Y, Ye L, et al. Exogenous peripheral blood mononuclear cells affect the healing process of deep degree burns. Molecular Medicine Reports. 2017 Dec 1;16(6):8110-22. https://doi.org/10.3892/mmr.2017.7672.
12. Grünwald B, Schoeps B, Krüger A. Recognizing the molecular multifunctionality and interactome of TIMP-1. Trends in Cell Biology. 2019 Jan 1;29(1):6-19. https://doi.org/10.1016/j.tcb.2018.08.006.
13. Brightwell CR, Hanson ME, El Ayadi A, et al. Thermal injury initiates pervasive fibrogenesis in skeletal muscle. Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C277-87. https://doi.org/10.1152/ajpcell.00337.2019.
14. Klimm W, Szamotulska K, Karwański M, et al. Tissue inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as new markers of acute kidney injury after massive burns. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2024 May 6;30:e943500-1. https://doi.org/10.12659/MSM.943500.
15. Rehou S, Jeschke MG. Admission creatinine is associated with poor outcomes in burn patients. Burns. 2022 Sep 1;48(6):1355-63. https://doi.org/10.1016/j.burns.2021.07.022.
16. Kim Y, Cho YS, Kym D, et al. Diagnostic performance of plasma and urine neutrophil gelatinase-associated lipocalin, cystatin C, and creatinine for acute kidney injury in burn patients: A prospective cohort study. PloS one. 2018 Jun 26;13(6):e0199600. https://doi.org/10.1371/journal.pone.0199600.
17. Khandelwal A, Satariano M, Doshi K, et al. Management and outcomes of acute kidney injury due to burns: a literature review. Journal of Burn Care & Research. 2024 Mar 1;45(2):323-37. https://doi.org/10.1093/jbcr/irad121.
18. Zhu W, Xie X, Shu Z, et al. Prognostic Significance of the Serum Creatinine Level During the Shock Stage in Severe Burn Patients: A 10‐Year Retrospective Study. Mediators of inflammation. 2025;2025(1):8876691. https://doi.org/10.1155/mi/8876691.
19. Kuang H, Wan HS, Gu QH, et al. Serum matrix metalloproteinase-9 levels and enzymatic activity in patients with anti-glomerular basement membrane disease. Front in Med. 2025 Nov 18; 12:1668791. https://doi.org/10.3389/fmed.2025.1668791.
20. Wozniak J, Floege J, Ostendorf T, et al. Key metalloproteinase-mediated pathways in the kidney. Nat Rev Nephrol. 2021 Aug;17(8):513-27. https://doi.org/10.1038/s41581-021-00415-5.
21. Kravets OV, Yekhalov VV, Gorbuntsov VV, et al. Kidney damage in burn disease. Part 1. Pathomorphophysiology (literature review). KIDNEYS. 2023 Dec 30;12(4):203-10. https://doi.org/10.22141/2307-1257.12.4.2023.430.
22. Rodríguez-Sánchez E, Navarro-García JA, Aceves-Ripoll J, et al. Association between renal dysfunction and metalloproteinase (MMP)-9 activity in hypertensive patients. Nefrología (English Edition). 2019 Mar 1;39(2):184-91. https://doi.org/10.1016/j.nefroe.2019.03.006.
23. La Russa A, Serra R, Faga T, et al. Kidney fibrosis and matrix metalloproteinases (MMPs). Front in B L. 2024 May 16;29(5):192. https://doi.org/10.31083/j.fbl2905192.
24. Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. I J Mol Sci. 2020 Dec 20;21(24):9739. https://doi.org/10.3390/ijms21249739.
25. Hasibuan LY, Prasetyo AT, Isytahar MA. Acute kidney injury in burn patients: A year findings from a topmost referral burn center in West Java, Indonesia. Burns Open. 2024 Jan 1;8(1):35-8. https://doi.org/10.1016/j.burnso.2023.12.004.
26. Demsey D, Mordhorst A, Griesdale DE, et al. Improved outcomes of renal injury following burn trauma. Burns. 2019 Aug 1;45(5):1024-30. https://doi.org/10.1016/j.burns.2019.04.001.
27. Clark AT, Li X, Kulangara R, et al. Acute kidney injury after burn: a cohort study from the parkland burn intensive care unit. JBCRes. 2019 Jan 1;40(1):72-8. https://doi.org/10.1093/jbcr/iry046.
28. Chen B, Zhao J, Zhang Z, et al. Clinical characteristics and risk factors for severe burns complicated by early acute kidney injury. Burns. 2020 Aug 1;46(5):1100-6. https://doi.org/10.1016/j.burns.2019.11.018.
29. Yang X, Tian X, Liu J, et al. Establishment of a prognostic nomogram model for acute predicting renal injury in patients with moderate and severe burns. Zhonghua wei Zhong Bing ji jiu yi xue. 2023 Jul 1;35(7):736-40. https://doi.org/10.3760/cma.j.cn121430-20220616-00577 .
30. Huang H, Lin Q, Dai X, et al. Derivation and validation of urinary TIMP-1 for the prediction of acute kidney injury and mortality in critically ill children. J Trans. Med.2022 Feb 23;20(1):102. https://doi.org/10.1186/s12967-022-03302-0.
31.Wang M, Zhang Q, Zhao X, et al. Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study. Critical Care. 2014 Nov 19;18(6):634. https://doi.org/10.1186/s13054-014-0634-6
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