Inorganic Nitrate May Reduce Contrast-Induced Nephropathy Risk

Inorganic nitrate may reduce the risk for contrast-induced nephropathy (CIN), help stabilize post-procedure kidney function, and reduce the risk for major adverse cardiac events (MACE) in at-risk patients undergoing coronary angiography for non-ST-elevation acute coronary syndrome, according to trial findings presented at the European Society of Cardiology Congress 2023.

In the double-blind NITRATE-CIN trial, investigators randomly assigned 319 patients to once daily potassium nitrate (12 mmol) and 321 patients to placebo (potassium chloride) capsules for 5 days. All patients received standard care for CIN prevention, including pre- and post-procedural hydration and use of low-osmolar contrast media.

Inorganic nitrate treatment significantly reduced the odds of CIN by 79% after adjustment for baseline creatinine and diabetes status, Dan Jones, MD, PhD, of Queen Mary University of London, UK, reported on behalf of his team. The rate of CIN was 9.1% in the treatment group compared with 30.5% in the placebo group.

The investigators defined CIN — also referred to as contrast-associated acute kidney injury — according to KDIGO criteria: a 0.3 mg/dL increase in creatinine within 48 hours or 1.5-fold increase within 1 week.

Procedural myocardial infarction was significantly less frequent in the treatment group (2.7% vs 12.5%) as was the occurrence of MACE within 12 months (9.1% vs 18.1%), Dr Jones reported. The MACE composite endpoint included death, non-fatal myocardial infarction, or unscheduled revascularization.

Mean estimated glomerular filtration rate (eGFR) at 3 months after the procedure was 5.17 mL/min/1.73m² higher in the inorganic nitrate group.

Nitric oxide might be deficient in contrast-associated AKI, according to background information on the study published in the Journal of Cardiovascular Pharmacology and Therapeutics.² Metabolized inorganic nitrate delivers nitric oxide to blood vessels and may exert renoprotective effects by reducing oxidative stress and inflammatory responses, according to preclinical research published in Redox Biology.³ Dietary sources of nitric oxide include beetroot and green leafy vegetables.

Patients at increased risk for CIN included those with an eGFR less than 60 mL/min/1.73m² or with at least 2 of the following risk factors: diabetes, liver failure (cirrhosis), age older than 70 years, exposure to contrast in the last 7 days, heart failure (or left ventricular ejection fraction less than 40%), and concomitant renally active drugs. Among trial patients, 45.9% had diabetes, 56.0% had stage 3 or higher chronic kidney disease, and the mean Mehran score was 10. The mean age of cohort was 71.0 years, 73.3% were men, and 75.2% were White.

“These findings could have important implications for health systems by reducing the burden of CIN and the associated prolonged admissions, dialysis, and significant costs,” according to Dr Jones.

References

1. Inorganic nitrate improves safety of coronary angiography in patients at renal injury risk: NITRATE-CIN trial presented in a Hot Line session today at ESC Congress 2023. News release. European Society of Cardiology; August 28, 2023.
2. Beirne AM, Mitchelmore O, Palma S, et al. NITRATE-CIN Study: Protocol of a randomized (1:1) single-center, UK, double-blind placebo-controlled trial testing the effect of inorganic nitrate on contrast-induced nephropathy in patients undergoing coronary angiography for acute coronary syndromes. J Cardiovasc Pharmacol Ther. 2021;26:303-309.
3. Yang T, Zhang XM, Tarnawski L, et al. Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress. Redox Biol. 2017;13:320-330.