Association Between Ferroptosis and Acute Kidney Disease (AKD): Unveiling the Expression of Genes Related to Iron Regulatory Metabolism.

Acute kidney disease (AKD), a condition between AKI and CKD, was categorized as a separate entity by KDIGO in 2012, although it remains debatable. The present study investigates mechanism underlying AKD condition with ferroptosis, lipid peroxidation and related genes. Blood samples were collected from AKD patients (n = 100) along with age and gender matched control. Expression analysis of GPX4, EPO, TF, HP, FTH1, NCOA4 genes was done using RT-PCR. Peroxidase activity, lipid peroxidation, serum ferritin and total protein were measured. Relative expressions of GPX4, EPO and TF were downregulated (P < 0.001) while FTH1, HP and NCOA4 expression were upregulated (P < 0.001) in AKD group compared to controls. Similar trend was observed between male AKD group versus male control (P < 0.001) and female AKD group versus female controls (P < 0.001). Expression deregulation of selected genes was detected in both age groups (≤ 40 year & > 40 year age) of AKD patents compared to their respective controls. AKD group showed significant (P < 0.001) increase in serum ferritin levels compared to respective control. Low activity of POD and elevated levels of lipid peroxidation was observed in male (P < 0.001) and female (P < 0.01) AKD patients compared to controls. Present study suggested a positive contribution of lipid-mediated ferroptosis in progression of AKD. Furthermore, expression deregulation of genes underlying iron metabolism along with depleted expression of antioxidant gene and low peroxidase activity postulated iron overload as possible candidate in etiology of AKD condition.