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

Hiba S Al-Amodi; Shimaa Abdelsattar; Zeinab A Kasemy; Hanan M Bedair; Hany S Elbarbary; Hala F M Kamel

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

Front Mol Biosci. 2021 Oct 6:8:751299. doi: 10.3389/fmolb.2021.751299. eCollection 2021.

Authors

Hiba S Al-Amodi¹, Shimaa Abdelsattar², Zeinab A Kasemy³, Hanan M Bedair⁴, Hany S Elbarbary^{5

6}, Hala F M Kamel^{1

7}

Affiliations

¹ Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
² Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt.
³ Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt.
⁴ Clinical Pathology Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt.
⁵ Department of Internal Medicine, Renal Unit, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt.
⁶ Department of Internal Medicine, Renal Unit, Faculty of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
⁷ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

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.