Inorganic nitrate reduces contrast-induced nephropathy in high-risk patients
The terminology used in this article summary reflects that used in the original. You can read a critique of the article by Jemima Scott here.
Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI), refers to a deterioration in renal function after contrast exposure. It is a serious complication of coronary angiography, with an incidence of up to 55% in high-risk people, such as those with older age, heart failure, CKD or diabetes with CKD. CIN is associated with longer hospital stays, increased risk of myocardial infarction (MI) and higher mortality.
The pathophysiology of CIN is uncertain, but early evidence suggests that contrast media generate oxidative stress which decrease levels of protective nitric oxide (NO), and that strategies to replace NO may be beneficial. Inorganic nitrate is reduced in the body to NO, which preclinical studies have shown to have renoprotective effects.
The NITRATE-CIN trial assessed the potential therapeutic benefit of inorganic nitrate in the prevention of CIN in people with acute coronary syndromes referred for invasive coronary angiography and at risk of CIN. Risk of CIN was defined as an eGFR <60 mL/min/1.73 m2 or two of the following: diabetes, liver failure, age >70 years, exposure to contrast in the last 7 days, heart failure (or left ventricular ejection fraction <40%) and concomitant renally active drugs.
The double-blind, placebo-controlled trial was conducted over 3 years at a single centre in London. Participants (n=640) were randomised 1:1 to receive once-daily potassium nitrate (12 mmol) or placebo capsules (potassium chloride) for 5 days.
Mean age was 71.0 years, 73.3% were men, 75.2% were White, 45.9% had diabetes, 56.0% had CKD and mean Mehran score was 10. The first dose was taken prior to coronary angiography.
The overall rate of the primary endpoint of CIN (as defined by the KDIGO criteria for AKI) was 20.0%, the majority of which were stage 1 (91.9%). The proportion of participants experiencing CIN was significantly reduced in the treatment group (9.1%) compared to the placebo group (30.5%; P<0.001). This difference persisted after adjustment for baseline creatinine and diabetes status (OR, 0.21; 95% CI, 0.13–0.34).
Secondary outcomes were also improved with inorganic nitrate. There were lower rates of procedural MI (2.7% vs 12.5%; P=0.003), improved 3-month renal function (between-group change in eGFR, 5.17 [2.94–7.39]) and reduced major adverse cardiac events at 12 months (9.1%vs 18.1%; P=0.001) compared to placebo.
The authors conclude that this simple, low-cost intervention may offer an important therapeutic option for patients undergoing angiography who are at risk of kidney injury following an acute cardiac event.
The full article can be read here.
