Perioperative Use of NAC to Prevent AKI in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery

Perioperative Use of N-acetylcysteine to Prevent Acute Kidney Injury in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery

Acute kidney injury (AKI) or renal impairment is an established complication of cardiac surgery occurring with an incidence up to 30%, To date, no agent has conferred renal protection. Considerable interest has developed in the potential for Nacetylcysteine (NAC) to exert a renoprotective effect in patients undergoing cardiac surgery. Due to the beneficial effect of NAC on contrast nephropathy and its reported anti-inflammatory effects.

Study Overview

• Status: Recruiting
• Conditions: Kidney Injury, Acute
• Intervention / Treatment: Other: Control Group

Detailed Description

Acute kidney injury (AKI), is a well-known complication of cardiac surgery, with an incidence of up to 30% depending on the definition. AKI caused by cardiac surgery is the second most common cause of AKI in the intensive care unit and is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB).

The pathogenesis of AKI after CPB is multifactorial, and is mostly due to hypo perfusion, reperfusion injury, activation of the systemic inflammatory response, and/or low cardiac output. Reperfusion will result in the formation of reactive oxygen species, resulting in injury to tissues.

The activation of the systemic inflammatory response is mostly due to the exposure of blood to the extracorporeal CPB circuit, resulting in the activation of the immune system, which is also mediated by the generation of reactive oxygen species. This results in increased recruitment of neutrophils, macrophages, and lymphocytes into the renal parenchyma, leading to AKI.

N-acetylcysteine (NAC) is well known for its antioxidant and free-radical scavenging properties, as well as its vasodilator properties. Its antioxidant properties enable it to prevent ischemic cell death, and as a free-radical scavenger, NAC mitigates the effect of increased reactive oxygen species caused by reperfusion. Hence, theoretically, NAC is able to counteract several mechanisms of kidney injury during cardiac surgery, namely, the systemic inflammatory response, free-radical injury, and ischemia.

In this study, we aimed to investigate if the perioperative use of acetylcysteine will prevent kidney injury after cardiac surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed A. Alhadidy, MD; Phone Number: M. 00201005092648; Email: Mohamed_alaaeldin@med.asu.edu.eg
• Study Contact Backup: Name: Adel M. Alansary, MD; Phone Number: 00201223954877; Email: adelalansary@med.asu.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • Recruiting
    • Cardiothoracic Academy, Ain Shams University Hospitals
    • Contact: University President; Phone Number: +2026847819; Email: gd.research@asu.edu.eg
    • Principal Investigator: Adel Alansary
    • Sub-Investigator: Ahmed Eldemerdash
    • Sub-Investigator: Mohamed Alhadidy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Scheduled for open heart Surgery with cardiopulmonary bypass (CPB) pump.
• Pre-existing moderate renal insufficiency serum creatinine more than 1.5 mg/dL

Exclusion Criteria:

• Patients on hemodialysis preoperatively
• History of renal transplantation
• IV contrast within 4 days prior to surgery
• Urgent/emergent surgery
• Preoperative hemodynamic instability (intra-aortic balloon pump support or vasoactive medications)
• Planned off-pump surgery;
• Planned deep-hypothermic-circulatory-arrest
• known or suspected allergy to NAC
• Patient Refusal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetylcysteine group; (23 Patients) Patients will recieve N-acetylcysteine 600 mg intravenous(IV) every 12 hours 24 hours before surgery and will be continued for 48 hours after surgery	Other: Control Group; Patients will not receive N-Acetylcystiene and will receive standard care according to our institutional protocol
No Intervention: Standard group; Patients will not receive N-Acetylcysteine and will receive standard care according to our institutional protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Creatinine rise	Creatinine increase >25% or ≥ 0.5 mg/dl above baseline	7days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RRT	Need for Renal Replacement Therapy	7 days
Length of ICU stay	Length of stay in the ICU in days	3 days
Length of hospital stay	Length of stay in hospital in days	7 to 10 Days
Mortality	Mortality rate	30 days
Adverse effects	Occurrence of NAC adverse effects as (bronchospasm, urticaria, facial edema, nausea/vomiting).	2 days

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Mohamed A. Alhadidy, Ain Shams University

Publications and helpful links

General Publications

• Lee SH, Kim SJ, Kim HJ, Son JS, Lee R, Yoon TG. Acute Kidney Injury Following Cardiopulmonary Bypass in Children - Risk Factors and Outcomes. Circ J. 2017 Sep 25;81(10):1522-1527. doi: 10.1253/circj.CJ-17-0075. Epub 2017 May 17.
• Schopka S, Diez C, Camboni D, Floerchinger B, Schmid C, Hilker M. Impact of cardiopulmonary bypass on acute kidney injury following coronary artery bypass grafting: a matched pair analysis. J Cardiothorac Surg. 2014 Jan 18;9:20. doi: 10.1186/1749-8090-9-20.
• Dexter F. Duration of cardiopulmonary bypass and outcome. J Cardiothorac Vasc Anesth. 2012 Apr;26(2):e19; author reply e19-20. doi: 10.1053/j.jvca.2011.12.012. Epub 2012 Jan 29. No abstract available.
• Nadim MK, Forni LG, Bihorac A, Hobson C, Koyner JL, Shaw A, Arnaoutakis GJ, Ding X, Engelman DT, Gasparovic H, Gasparovic V, Herzog CA, Kashani K, Katz N, Liu KD, Mehta RL, Ostermann M, Pannu N, Pickkers P, Price S, Ricci Z, Rich JB, Sajja LR, Weaver FA, Zarbock A, Ronco C, Kellum JA. Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group. J Am Heart Assoc. 2018 Jun 1;7(11):e008834. doi: 10.1161/JAHA.118.008834. No abstract available.
• Ates B, Abraham L, Ercal N. Antioxidant and free radical scavenging properties of N-acetylcysteine amide (NACA) and comparison with N-acetylcysteine (NAC). Free Radic Res. 2008 Apr;42(4):372-7. doi: 10.1080/10715760801998638.
• Nigwekar SU, Kandula P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac Surg. 2009 Jan;87(1):139-47. doi: 10.1016/j.athoracsur.2008.09.026.
• Savluk OF, Guzelmeric F, Yavuz Y, Cevirme D, Gurcu E, Ogus H, Orki T, Kocak T. N-acetylcysteine versus Dopamine to Prevent Acute Kidney Injury after Cardiac Surgery in Patients with Preexisting Moderate Renal Insufficiency. Braz J Cardiovasc Surg. 2017 Jan-Feb;32(1):8-14. doi: 10.21470/1678-9741-2016-0028.
• Kotlyar E, Keogh AM, Thavapalachandran S, Allada CS, Sharp J, Dias L, Muller D. Prehydration alone is sufficient to prevent contrast-induced nephropathy after day-only angiography procedures--a randomised controlled trial. Heart Lung Circ. 2005 Dec;14(4):245-51. doi: 10.1016/j.hlc.2005.06.007. Epub 2005 Oct 3.
• Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol. 2002 Feb 1;89(3):356-8. doi: 10.1016/s0002-9149(01)02243-3. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Anticipated): November 26, 2022
• Study Completion (Anticipated): December 26, 2022

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Acute kidney injury; Cardiac surgery; N-acetylcysteine
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: FMASU R 122/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No