Inhaled nitric oxide prevents NSAID-induced renal impairment in pseudo-normovolaemic piglets.

Stephane Junot,Eric Troncy,Jeanne-Marie Bonnet-Garin,Jean-Yves Ayoub,Stephanie Keroak,Christian Paquet,Jerome R E Del Castillo,Aftab Ahmad

doi:10.1371/journal.pone.0179475

Abstract

ObjectiveInhaled nitric oxide (iNO) is commonly used as a treatment of pulmonary hypertension. Its action is purported to be specific to the lung, but extrapulmonary effects have been reported. The objective of this study was to evaluate if iNO could compensate the renal impairment induced by ketoprofen, a conventional non-steroidal anti-inflammatory drug (NSAID), during general anaesthesia.MethodsUnder pseudo-normovolaemic condition, thirty piglets were randomly assigned into 5 equal groups and equipped for renal and systemic parameters measurements. A first experiment was carried out to validate methods and reproduce the renal effects of iNO (40 ppm) in comparison with a placebo (100% oxygen). In a second experiment, iNO was inhaled for 120 minutes right after NSAID treatment (ketoprofen 2 mg×kg-1 IV, and 40 ppm iNO; group KiNO) and its effects were compared to ketoprofen alone (2 mg×kg-1 IV; group K) and placebo (saline; group C).ResultsIn this model, iNO increased significantly renal blood flow measured by ultrasonic (RBFUL: +53.2±17.2%; p = 0.008) and by PAH clearance (RBFPAH:+78.6±37.6%; p = 0.004) methods, glomerular filtration rate (GFR: +72.6±32.5%; p = 0.006) and urinary output (UO: +47.4±24.2%; p = 0.01). In the second experiment, no significant temporal variation was noted for renal parameters in groups KiNO and C, whereas a significant and constant decrease was observed in the group K for RBFUL (max -19.0±7.1%), GFR (max -26.6±10.4%) and UO (max -30.3±10.5%).Clinical significanceOur experiments show that iNO, released from its transport forms after its inhalation, can improve renal safety of NSAIDs. This result is promising regarding the use of NSAIDs in critical conditions, but needs to receive clinical confirmation.

Highlights

Acute kidney injury (AKI) is defined as a rapid deterioration in renal function, it is a common complication in the perioperative settings and is associated with an increased morbidity and mortality [1]
INO increased significantly renal blood flow measured by ultrasonic (RBFUL: +53.2±17.2%; p = 0.008) and by para-amino hippuric acid (PAH) clearance (RBFPAH:+78.6±37.6%; p = 0.004) methods, glomerular filtration rate (GFR: +72.6±32.5%; p = 0.006) and urinary output (UO: +47.4 ±24.2%; p = 0.01)
No significant temporal variation was noted for renal parameters in groups KiNO and C, whereas a significant and constant decrease was observed in the group K for RBFUL, GFR and UO

Summary

Introduction

Acute kidney injury (AKI) is defined as a rapid deterioration in renal function, it is a common complication in the perioperative settings and is associated with an increased morbidity and mortality [1]. It has been reported in 7 to 18% of hospitalized patients [2] and approximately one out of three AKI in hospitalised patients are acquired in the perioperative setting [3]. The blockage of prostanoid synthesis by NSAIDs, through the inhibition of the cyclooxygenase (COX) enzymes activity, explains their clinical efficacy and their renal side effects [7,8]. Preferential or selective inhibition of inducible COX-2 isoform has led to improved gastro-intestinal safety but is not denuded of renal side effects [11,12]

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Conclusion