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Inorganic Nitrates to Protect Against Contrast-Induced Nephropathy
Quick Takes
- NITRATE-CIN is a double-blind, placebo-controlled study assessing the effect of inorganic nitrate (oral potassium nitrate therapy—KNO3 for 5 days) on risk of contrast-induced nephropathy (CIN) among patients with ACS undergoing coronary angiography.
- Inclusion criteria included patients at risk of CIN defined as an eGFR <60 mL/min or two of the following: diabetes, liver failure (cirrhosis), age >70 years, exposure to contrast in last 7 days, heart failure (or LVEF <40%), and concomitant renally active drugs (diuretics, angiotensin receptor blockers). CIN was defined as ≥0.3 mg/dL or ≥26.5 μmol/L increase in creatinine within 48 hours or ≥1.5 times within 1 week, as defined by KDIGO criteria for acute kidney injury.
- KNO3 therapy was associated with a significant reduction in CIN (9.1% vs. 30.5%) and improved kidney outcomes at 3 months. There was also a reduction in MACE rates at 12 months (9.1% vs. 18.1%); however, the trial was not powered for this composite outcome.
Study Questions:
What is the efficacy of inorganic nitrate in the prevention of contrast-induced nephropathy (CIN) in high-risk patients presenting with acute coronary syndromes (ACS)?
Methods:
NITRATE-CIN is a double-blind, randomized, single-center, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (Kidney Disease Improving Global Outcomes [KDIGO] criteria). Secondary outcomes included kidney function (estimated glomerular filtration rate [eGFR]) at 3 months, rates of procedural myocardial infarction (MI), and major adverse cardiovascular events (MACE) at 12 months.
Results:
Over 3 years, 640 patients were randomized with a median follow-up of 1.0 year; 319 received inorganic nitrate and 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) versus placebo (30.5%, p < 0.001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio, 0.21; 95% confidence interval [CI], 0.13–0.34). Secondary outcomes were improved with inorganic nitrate, with 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; 95% CI, 2.94–7.39), and reduced 1-year MACE (9.1% vs. 18.1%, p = 0.001) vs. placebo.
Conclusions:
In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5-day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.
Perspective:
NITRATE-CIN is a double-blind, placebo-controlled study assessing the effect of inorganic nitrate (oral potassium nitrate therapy—KNO3 for 5 days) on risk of CIN among patients with ACS undergoing coronary angiography. Inclusion criteria included patients at risk of CIN defined as an eGFR <60 mL/min or two of the following: diabetes, liver failure (cirrhosis), age >70 years, exposure to contrast in last 7 days, heart failure (or left ventricular ejection fraction [LVEF} <40%), and concomitant renally active drugs (diuretics, angiotensin receptor blockers). CIN was defined as ≥0.3 mg/dL or ≥26.5 μmol/L increase in creatinine within 48 hours or ≥1.5 times within 1 week, as defined by KDIGO criteria for acute kidney injury.
KNO3 therapy was associated a with significant reduction in CIN (9.1% vs. 30.5%) and improved kidney outcomes at 3 months. There was also a reduction in MACE rates at 12 months (9.1% vs. 18.1%); however, the trial was not powered for this composite outcome. The findings are compelling and supported by prior studies showing reno-protective effects of inorganic nitrates. In addition to improved clinical outcomes, other advantages include tolerability and low cost of the therapy.
Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging, Prevention
Keywords: Acute Coronary Syndrome, Coronary Angiography, Nitrates
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