Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury

Cardiorenal Med. 2020;10(2):85-96. doi: 10.1159/000503718. Epub 2020 Jan 20.

Abstract

Background/aims: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients.

Methods: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model.

Results: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI.

Conclusion: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

Keywords: Acute kidney injury; Cardio renal; Myocardial infarction; Nitric oxide; Oxidative stress.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cardio-Renal Syndrome / complications
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / complications*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Natriuretic Peptide, Brain / metabolism
  • Nitric Oxide / metabolism*
  • Oxidative Stress / physiology
  • Percutaneous Coronary Intervention / adverse effects*
  • Percutaneous Coronary Intervention / methods
  • Predictive Value of Tests
  • ST Elevation Myocardial Infarction / physiopathology
  • ST Elevation Myocardial Infarction / surgery
  • Shock, Cardiogenic / complications
  • Shock, Cardiogenic / metabolism
  • Troponin / metabolism

Substances

  • Biomarkers
  • Troponin
  • Natriuretic Peptide, Brain
  • Nitric Oxide