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. 2018 Nov 15;198(10):1279-1287.
doi: 10.1164/rccm.201710-2150OC.

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery

Chong Lei  1 , Lorenzo Berra  2 , Emanuele Rezoagli  2   3 , Binglan Yu  2 , Hailong Dong  1 , Shiqiang Yu  4 , Lihong Hou  1 , Min Chen  1 , Wensheng Chen  4 , Hongbing Wang  4 , Qijun Zheng  4 , Jie Shen  1 , Zhenxiao Jin  4 , Tao Chen  4 , Rong Zhao  4 , Emily Christie  5 , Venkata S Sabbisetti  5 , Francesco Nordio  6 , Joseph V Bonventre  5 , Lize Xiong  1 , Warren M Zapol  2
Affiliations

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery

Chong Lei et al. Am J Respir Crit Care Med. .

Abstract

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery.

Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass.

Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively.

Measurements and main results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041).

Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

Keywords: acute kidney injury; chronic renal insufficiency; hemolysis; nitric oxide; rheumatic heart disease.

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Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials flow diagram: enrollment, allocation, and analysis. CPB = cardiopulmonary bypass; HES = hydroxyethyl starch; ITT = intention-to-treat.
Figure 2.
Figure 2.
Analysis of plasma hemolysis biomarkers. (A) Analysis of plasma Hb before and up to 48 hours after surgery. (B) Analysis of urine Hb before and up to 48 hours after surgery. (C) Analysis of plasma nitric oxide (NO) consumption before and up to 48 hours after surgery. Data are expressed as means with 95% confidence intervals. *P < 0.05 versus control group. CPB = cardiopulmonary bypass.
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