Potential Value of TNF-α (-376G/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,Hanan M Bedair,Hany S Elbarbary,Zeinab A Kasemy,Shimaa Abdelsattar,Hala F M Kamel

doi:10.3389/fmolb.2021.751299

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.

Highlights

Acute Kidney Injury (AKI) is one of the most common complications among septic patients in the intensive care unit (ICU) and is frequently associated with a higher risk of morbidity and mortality. (Uchino et al, 2005)
The simultaneous presence of sepsis and AKI might be described as Sepsis Associated Kidney Injury (S-AKI) (Bellomo et al, 2017), which has been recently defined as a rapid worsening of renal functions with the existence of sepsis, with no other reasonable explanation of etiology (Manrique-Caballero et al, 2021), considering that most of the septic patients developed AKI earlier than being diagnosed (Rosen and Samuel, 2001)
Ill patients recruited in the current study were categorized into two groups: sepsis group (No 84; 42%) and acute septic shock group (No 116; 58%) according to the new consensus definition of sepsis and septic shock, in which sepsis was diagnosed by the existence of possible infection within the first 24 h of admission to ICU and confirmed by blood culture, in addition to consecutive development of organ dysfunction, which was characterized by a rise of total Sequential Organ Failure Assessment (SOFA) score of ≥2 points

Summary

Introduction

Acute Kidney Injury (AKI) is one of the most common complications among septic patients in the intensive care unit (ICU) and is frequently associated with a higher risk of morbidity and mortality. (Uchino et al, 2005). Serum Creatinine (sCr) has been used as a gold standard for diagnosis of AKI, despite being affected by several biological factors such as age, sex, muscle build, and immobilization (Nejat et al, 2010a). Cystatin C (CysC) has been the subject of extensive focus as a potential biomarker for the early diagnosis and prediction of AKI or as an alternate to the gold standard “creatinine” (Lagos-Arevalo et al, 2015). It is a member of the cys¬tatin superfamily of protease inhibitors and is secreted via nucleated cells. In contrast to sCr, its levels are not considerably influenced by biological factors (Knight et al, 2004)

Objectives

Methods

Results

Conclusion