Renal Protective Effects and the Prevention of Contrast-Induced Nephropathy by Atrial Natriuretic Peptide - Renal Protective Effects and the Prevention of Contrast-Induced Nephropathy by Atrial Natriuretic Peptide

Mar 16, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Date Published:
01/01/2009
Date Updated:
03/16/2009
Original Posted Date:
03/16/2009
References

Description:

The goal of the trial was to evaluate infusion of atrial natriuretic peptide (ANP) and Ringer’s solution compared with Ringer’s solution alone in patients with renal insufficiency undergoing coronary angiography or percutaneous coronary intervention (PCI).

Hypothesis:

ANP and Ringer’s solution would be more effective in preventing contrast-induced nephropathy (CIN).

Study Design

  • Randomized
  • Parallel

Patients Screened: 272
Patients Enrolled: 254
Mean Follow Up: 1-month
Mean Patient Age: 74 years
Female: 29%
Mean Ejection Fraction: 52%

Patient Populations:

  • Patients undergoing coronary angiography or PCI between the ages of 20 and 85 years
  • Serum creatinine ≥1.3 mg/dl and <6 mg/dl

Exclusions:

  • Pregnancy
  • Lactation
  • Acute renal failure
  • End-stage renal failure on dialysis
  • Acute myocardial infarction
  • Multiple myeloma
  • Pulmonary edema
  • Cardiogenic shock
  • Systolic blood pressure <110 mm Hg
  • Dehydration
  • Allergy to contrast dye or ANP
  • Exposure to contrast dye within the last 7 days
  • Exposure to intravenous ANP with the last month
  • Parenteral use of diuretics
  • Current administration of dopamine, N-acetylcysteine, metformin, sodium bicarbonate, fenoldapam, mannitol, or nonsteroidal anti-inflammatory agents

Primary Endpoints:

  • CIN (25% increase or 0.5 mg/dl increase in creatinine) within 48 hours

Secondary Endpoints:

  • 25% increase in creatinine within 48 hours
  • 0.5 mg/dl increase in creatinine within 48 hours
  • Changes in serum creatinine, glomerular filtration rate, serum cystatin C concentration, β2-microglobulin, and N-acetyl-β-D-glucosaminidase
  • CIN at 1 month

Drug/Procedures Used:

Patients with serum creatinine ≥1.3 mg/dl who were undergoing coronary angiography or PCI were randomized to ANP (0.042 µg/kg/min) and Ringer’s solution (1.3 ml/kg/h) (n = 126) versus Ringer’s solution alone (n = 128). Study medications were administered 4-6 hours before and 48 hours after catheterization.

Concomitant Medications:

At baseline, there was no difference in the medications between the groups. Angiotensin-converting enzyme inhibitors were used in 16%, angiotensin-receptor blockers in 49%, calcium channel blockers in 62%, diuretics in 50%, and statins in 63%.

Principal Findings:

Overall, 261 patients were randomized. There was no difference in the baseline characteristics between the groups. The mean age was 74 years, 29% were women, 41% were diabetics, 45% had history of myocardial infarction, the mean left ventricular ejection fraction was 52%, and the mean volume of contrast media delivered was 139 ml.

The primary outcome, incidence of CIN at 48 hours (using percent or absolute change in creatinine) was 3.2% for the ANP and Ringer’s group versus 11.7% for the Ringer’s group alone (p = 0.015). For the components of this outcome, increase in serum creatinine ≥0.5 mg/dl (2.4% vs. 8.6%, p = 0.042) and increase in serum creatinine >25% from baseline (3.2% vs. 10.9%, p = 0.023), respectively for ANP versus control. Cystatin C was reduced from baseline to 48 hours (-0.03 vs. 0.03 mg/L, p = 0.042), up to 1 week (-0.01 vs. 0.09 mg/L, p = 0.0001), and up to 1 month (-0.02 vs. 0.04 mg/L, p = 0.015), respectively for ANP versus control.

By univariate analysis, use of ANP reduced the incidence of CIN, while use of more than 155 ml of contrast dye increased the incidence of CIN. ANP infusion decreased systolic blood pressure at 24 hours (-9.3 vs. -3.2 mm Hg, p < 0.001) and increased 2-day urine volume (4067 vs. 3686 ml, p = 0.042), respectively for ANP versus control.

Interpretation:

Infusion of ANP and Ringer’s solution for 4-6 hours before and 48 hours after catheterization was associated with a reduction in the incidence of CIN compared with Ringer’s solution alone. Cystatin C, a more sensitive measure of renal dysfunction, was also reduced at 48 hours, 1 week, and 1 month with ANP. While this trial was positive, other studies have demonstrated neutral results with ANP. Some of this difference may have been due to the shorter infusion duration in one study and excessive dosing in another study.

The incidence of CIN in the control arm (approximately 12%) despite more than 4 liters of fluid for a 70 kg patient is testament to the high prevalence of this condition and need for research.

N-acetylcysteine was initially greeted with enthusiasm, although the benefit of this agent is less clear than initially thought. Therefore, future studies are needed to more precisely determine the efficacy and safety of ANP. The blood pressure lowering effects of ANP will also need to be carefully monitored.

References:

Morikawa S, Sone T, Tsuboi H, et al. Renal protective effects and the prevention of contrast-induced nephropathy by atrial natriuretic peptide. J Am Coll Cardiol 2009;53:1040-6.

Clinical Topics: Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Angiotensin Receptor Antagonists, Myocardial Infarction, Diuretics, Coronary Disease, Blood Pressure, Creatinine, Calcium Channel Blockers, Percutaneous Coronary Intervention, Contrast Media, Prevalence, Renal Insufficiency, Kidney Diseases, Coronary Angiography, Catheterization, Stroke Volume, Isotonic Solutions, Atrial Natriuretic Factor, Cystatin C, Diabetes Mellitus


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