Compound in Beetroot Juice Fends Off Contrast-Induced AKI

AMSTERDAM -- An oral nitrate pill reduced contrast-induced acute kidney injury (AKI) when given to heart attack patients before they underwent invasive coronary angiography, the single-center NITRATE-CIN trial showed.

In people with non-ST-elevation acute coronary syndrome (NSTE-ACS), the inorganic nitrate supplement was associated with reduced contrast-induced nephropathy (CIN) at 12 months when compared with placebo (9.1% vs 30.5%, P<0.0001).

Three-month trends in creatinine and eGFR improvements favored the inorganic nitrate group, as did major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, and unplanned revascularizations) and major adverse kidney events (all-cause mortality, renal replacement therapy, and persistent renal dysfunction defined as a >50% increase in baseline serum creatinine) at 1 year.

"These findings could have important implications in reducing the burden of CIN on healthcare systems worldwide," said Dan Jones, MBBS, PhD, of Queen Mary University of London, during the European Society of Cardiology (ESC) Congress.

Deepak Bhatt, MD, MPH, of Mount Sinai Heart in New York City, called the trial's results "very interesting and provocative," citing the reported 60% reduction in kidney events and 50% reduction in cardiac events.

"As these results would affect millions of patients worldwide, it would be wise to replicate the study. If the effect sizes seen here are real, such replication would not require large trials," said Bhatt, who was not involved with NITRATE-CIN.

Jones also suggested that future studies powered to detect differences in MACE are needed to confirm inorganic nitrate's potential benefit -- which could address an unmet need, since contrast-associated AKI is a longstanding problem in coronary angiography or percutaneous coronary intervention.

Researchers have searched for years for a way to prevent such renal injury besides hydration, and one after another of these attempts has failed (e.g., intravenous sodium bicarbonate and oral N-acetylcysteine, the contrast-diverting Avert system).

As such, certain patient groups undergoing invasive coronary angiography -- including those with lower eGFR, diabetes, older age, and heart failure -- are left at elevated risk of developing this complication. In turn, AKI is associated with longer hospital stays, increased risk for renal replacement therapy, recurrent revascularization procedures, and higher mortality.

It is thought that dietary inorganic nitrate may be helpful as it replaces the lost nitric oxide that is thought to contribute to AKI.

During a press conference, Jones described the nitrate intervention in NITRATE-CIN as a capsule taken orally with the nitrate content comparable to two shots of beetroot juice. These potassium nitrate capsules brought nitrate and nitrite levels several-fold higher within hours, and their subsequent withdrawal led to a return to baseline levels at 3 months, he reported.

Notably, there was an interaction in the subgroup of people with prior organic nitrate use, who did not appear to have a CIN reduction from the nitrate provided in the trial, Jones said.

NITRATE-CIN was conducted at St. Bartholomew's Hospital in London and randomized 640 NSTE-ACS patients undergoing invasive coronary angiography who met varying criteria for greater risk of CIN, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria based on serum creatinine increases.

Patients who were hemodynamically or clinically unstable, or already had kidney dysfunction reach the point of eGFR <20/min or need for renal replacement therapy, were excluded.

Eligible participants were randomized to potassium nitrate or potassium chloride placebo for 5 days.

Mean age was 71 years, and just over a quarter were women. Over half had chronic kidney disease at baseline, and 45% had diabetes.

Contrast use averaged around 175 mL per person between the two groups, and average Mehran score was 10 (indicating high end of medium risk of AKI).

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