Protective Effects of Melatonin on Kidney Function Against Contrast Media‐Induced Kidney Damage in Patients With Chronic Kidney Disease: A Prospective, Randomized, Double‐Blinded, Placebo‐Controlled Trial

ABSTRACT Patients with chronic kidney disease (CKD) are at increased risk of acute kidney injury following exposure to contrast media. We evaluated the effect of melatonin, a potent antioxidant, as a protective strategy against contrast‐induced acute kidney injury (CI‐AKI), with a focus on molecular mechanisms. We randomized patients with an eGFR < 60 mL/min/1.73 m 2 undergoing coronary angiography (CAG) into melatonin (10 mg twice daily) or placebo groups. Treatment started 48 h before CAG and continued for a total of 6 days. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, at the time of CAG, and at 6, 24, 48, 72 h, and Day 30 post‐procedure. The primary outcome was the incidence of CI‐AKI; secondary outcomes included kidney function, oxidative stress, mitochondrial function, and cell death pathways. Forty patients were randomized into either the treatment or placebo group. All subsequent analyses were conducted on an as‐treat basis. The incidence of CI‐AKI was significantly lower in the melatonin group compared to the placebo group (25% vs. 60%, p = 0.025). The melatonin group showed a significantly smaller percentage change in plasma neutrophil gelatinase‐associated lipocalin (NGAL) at all time points. In the PBMC study, cellular oxidative stress was significantly reduced in the melatonin group at each time point, and mitochondrial oxidative stress was lower at 48–72 h. Mitochondrial respiration improved significantly, and both necrosis and necroptosis were reduced at 24 h. Melatonin administration effectively reduced the incidence of CI‐AKI in CKD patients undergoing CAG. This protective effect was associated with decreased oxidative stress, enhanced mitochondrial function, and reduced cell death, suggesting melatonin as a promising preventive strategy for CI‐AKI. Trial Registration: TCTR20210123004