The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress,vascular dysfunction and apoptosis independent of glycaemia

Contrast‐induced nephropathy (CIN) is a leading cause of hospital‐acquired acute kidney injury, particularly in diabetic patients. Previous studies have shown renoprotective effects of glucagon‐like peptide‐1 (GLP‐1) signalling; however, its role in CIN remains unexplored. This study investigates the prophylactic effect of exendin‐4, a GLP‐1R agonist, against CIN in a rat model mimicking both healthy and diabetic conditions. Animals were randomly divided into 7 groups: a control sham group (n = 8), and 2 identical sets of 3 disease groups, one received exendin‐4 before exposure to contrast medium (CM), while the other served as untreated control. The 3 disease groups represented diabetes (n = 8), CIN (n = 8), or diabetes and CIN combined (n = 8). Untreated groups showed deteriorating renal function as indicated by significantly higher levels of serum creatinine and blood urea nitrogen, malondialdehyde, and endothelin‐1 and caspase‐3 expression compared to the sham control group. This was accompanied by a significant decrease in tissue reserves of reduced glutathione, superoxide dismutase, nitrate and endothelin nitric oxide synthase as well as deteriorating renal histology. The CM‐induced changes in diabetic rats indicate impaired renal function, oxidative stress, vascular dysfunction, and apoptosis, and were significance higher in intensity compared to non‐diabetic rats. Pretreatment with exendin‐4 ameliorated all the aforementioned CM‐induced nephropathic effects independent of the glycemic state. To our knowledge, this is the first study describing the prophylactic renoprotective effects of exendin‐4 against CIN. With the current pharmaceutical use of exendin‐4 as a hypoglycaemic agent, the GLP‐1R agonist becomes an interesting candidate for human clinical trials on CIN prevention.