Abstract 4370479: Tocilizumab: Potential Protective Effects Against Acute Kidney Injury and Cardiorenal Dysfunction

Abstract

Cardiovascular diseases can lead to acute kidney injury (AKI) through cardiorenal syndrome by reducing renal blood flow and increasing venous congestion. According to the Kidney Disease: Improving Global Outcomes (KDIGO, 2012), during hospitalization, 1 in 5 adults developed acute kidney injury (AKI), caused by renal insults that lead to oxidative stress. Such events can trigger changes in the mitochondrial respiratory chain, inducing apoptosis, structural abnormalities in cells and their organelles, and even mitochondrial DNA instability. In this context, Tocilizumab is a monoclonal antibody that inhibits interleukin-6 (IL-6). Hipotesis: To evaluate the effect of Tocilizumab on renal function and oxidative profile in rats with ischemia-reperfusion-induced acute kidney injury (IR-AKI). Methodology: male adult Wistar rats, divided into 4 groups (N=7): Control (SHAM); TCZ (Tocilizumab; 4 mg/kg, i.p.; single dose); Ischemia and Reperfusion (I/R; clamping of the renal pedicles); TCZ+I/R (Tocilizumab treatment followed by ischemia). Renal function was assessed by serum and urinary creatinine levels and inulin clearance, as well as the oxidative profile. This study was approved by the Animal Use Ethics Committee (CEUA), under protocol number 2014/2023. Results: The analyses showed a significant reduction in serum creatinine levels and an increase in inulin clearance in the TCZ+I/R group compared to the I/R group. Regarding the oxidative profile, analyzed through the FOX and TBARS methods, an increase in urinary peroxides was observed in the TCZ group compared to the SHAM group, while a significant reduction was noted in the TCZ+I/R group compared to the I/R group. The urinary nitrate test revealed lower expression in the TCZ+I/R group. Similarly, the thiol test demonstrated reduced antioxidant activity in the TCZ+I/R group compared to the treated control groups. Discussion: Tocilizumab (TCZ) is an important IL-6 inhibitor, since IL-6 plays a key role in renal inflammatory responses, both in acute and chronic processes. In this study, the use of this drug proved to be promising for the prevention of IR-AKI, by inhibiting a key mediator involved in the amplification of inflammation. Conclusion: In conclusion, the Tocilizumab demonstrated a renoprotective effect, improving renal function and reducing oxidative activity. It presents itself as a potential adjuvant therapy in conditions with a risk of renal ischemia, such as kidney transplantation.