Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients
- PMID: 34692772
- PMCID: PMC8526786
- DOI: 10.3389/fmolb.2021.751299
Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients
Abstract
Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (-376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (-376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (-376 G/A) SNP between S-AKI and non-AKI patients (p < 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p = 0.011). The combination of both sCysC and TNF-α (-376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= < 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p < 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
Keywords: TNF-α; critically ill patients; cystatin C; polymorphism; sepsis associated acute kidney injury.
Copyright © 2021 Al-Amodi, Abdelsattar, Kasemy, Bedair, Elbarbary and Kamel.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures



Similar articles
-
Genotype-Phenotype Correlation of TNF-α (-238, rs361525) and Cystatin C for Early Detection of Sepsis-Associated AKI and Its Severity in Critically Ill Neonates.Int J Mol Sci. 2025 Jul 14;26(14):6738. doi: 10.3390/ijms26146738. Int J Mol Sci. 2025. PMID: 40724987 Free PMC article.
-
Association of TNF-α-308 (G >A) (rs1800629) Gene Polymorphism with Adverse Outcomes of Sepsis in Critically Ill Patients.DNA Cell Biol. 2020 Sep;39(9):1723-1729. doi: 10.1089/dna.2020.5468. Epub 2020 Jul 17. DNA Cell Biol. 2020. PMID: 32700971
-
Serum N-terminal pro-B-type natriuretic peptide and cystatin C for acute kidney injury detection in critically ill adults in China: a prospective, observational study.BMJ Open. 2023 Jan 30;13(1):e063896. doi: 10.1136/bmjopen-2022-063896. BMJ Open. 2023. PMID: 36717146 Free PMC article.
-
Impact of severe sepsis on serum and urinary biomarkers of acute kidney injury in critically ill children: an observational study.Blood Purif. 2013;35(1-3):172-6. doi: 10.1159/000346629. Epub 2013 Feb 15. Blood Purif. 2013. PMID: 23428967
-
Sepsis-mediated renal dysfunction: Pathophysiology, biomarkers and role of phytoconstituents in its management.Biomed Pharmacother. 2023 Sep;165:115183. doi: 10.1016/j.biopha.2023.115183. Epub 2023 Jul 22. Biomed Pharmacother. 2023. PMID: 37487442 Review.
Cited by
-
Comparative analysis of TNF-α (-308) gene polymorphism in Turkish patients with type 2 diabetes developing nephropathy and/or neuropathy.Sci Rep. 2024 Dec 30;14(1):31731. doi: 10.1038/s41598-024-82773-1. Sci Rep. 2024. PMID: 39738562 Free PMC article.
-
Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns Trauma. 2024 May 6;12:tkae006. doi: 10.1093/burnst/tkae006. eCollection 2024. Burns Trauma. 2024. PMID: 38716051 Free PMC article. Review.
-
An early warning model to predict acute kidney injury in sepsis patients with prior hypertension.Heliyon. 2024 Jan 10;10(2):e24227. doi: 10.1016/j.heliyon.2024.e24227. eCollection 2024 Jan 30. Heliyon. 2024. PMID: 38293505 Free PMC article.
-
Predictive nomogram model for major adverse kidney events within 30 days in sepsis patients with type 2 diabetes mellitus.Front Endocrinol (Lausanne). 2022 Dec 16;13:1024500. doi: 10.3389/fendo.2022.1024500. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36589822 Free PMC article.
-
The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury.Open Life Sci. 2023 Aug 31;18(1):20220700. doi: 10.1515/biol-2022-0700. eCollection 2023. Open Life Sci. 2023. PMID: 37671089 Free PMC article. Review.
References
LinkOut - more resources
Full Text Sources
Miscellaneous