Evaluating the Effect of Acetazolamide on the Prevention of Post-operative Acute Kidney Injury after Coronary Artery Bypass Grafting Surgery: A Randomized, Open-labeled Clinical Trial

Document Type : Research article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Clinical Research and Development Center at Shahid Modarress Hospital, Department of Cardiac Surgery, Shahid Beheshti of Medical Sciences, Tehran, Iran.

3 Department of Cardiovascular Surgery, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Nephrology and Kidney Transplantation, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid beheshti University of Medical Sciences, Tehran, Iran

6 Chronic Respiratory Diseases Research center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

10.22037/ijpr.2021.115334.15323

Abstract

Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG) surgery and can be linked to the increased morbidity and mortality. Therefore, in the present study, the effect of preoperative administration of acetazolamide was evaluated to investigate whether it could prevent occurrence of post-operative AKI after CABG surgery. In this randomized controlled clinical trial, 130 patients who were candidates to undergo elective CABG surgery from January 21, 2020 to February 8, 2021 were randomly allocated to intervention group (receiving 500 mg of acetazolamide orally 2 h preoperatively) and control group. The patients were evaluated for AKI based on the kidney disease- improving global outcomes (KDIGO) criteria based on their serum creatinine (SCr) level and urine output until 7 days postoperatively. There was no significant difference in baseline demographics between the two groups. The total incidence of AKI was measured as 43%. Analysis of post-operative AKI incidence showed no statistically significant difference between the two groups (P = 0.860). Mean post-operative SCr level on day 1 was significantly higher in the acetazolamide group (P = 0.036). A significant difference was found in length of hospitalization stay between the groups, which was higher in the control group (P = 0.006). Our results did not demonstrate a significant protective effect of acetazolamide on incidence of post-operative AKI in the patients undergone elective on-pump CABG surgery.

Graphical Abstract

Evaluating the Effect of Acetazolamide on the Prevention of Post-operative Acute Kidney Injury after Coronary Artery Bypass Grafting Surgery: A Randomized, Open-labeled Clinical Trial

Keywords


(1) Melly L, Torregrossa G, Lee T, Jansens JL and
Puskas JD. Fifty years of coronary artery bypass
grafting. J. Thorac. Dis. (2018) 10: 1960-7.
(2) Montrief T, Koyfman A and Long B. Coronary
artery bypass graft surgery complications: A
review for emergency clinicians. Am. J. Emerg.
Med. (2018) 36: 2289-97.
(3) Wu B, Chen J and Yang Y. Biomarkers of Acute
Kidney Injury after Cardiac Surgery: A Narrative
Review. Biomed Res. Int. (2019) 2019: 7298635.
(4) Barzi F, Miri R, Sadeghi R, Sistanizad M, Sadeghi
M, Mahjoob MP and Chehrazi MJ. A randomized
double blind placebo controlled trial examining
the effects of pentoxifylline on contrast induced
nephropathy reduction after percutaneous coronary
intervention in high risk candidates. Iran. J. Pharm.
Res. (2019) 18: 1040-6.
(5) Yuan SM. Acute kidney injury after cardiac
surgery: Risk factors and novel biomarkers. Braz.
J. Cardiovasc. Surg. (2019) 34: 352-60.
(6) Ho KM and Power BM. Benefits and risks of
furosemide in acute kidney injury. Anaesthesia.
(2010) 65: 283-93.
(7) Nouri-Majalan N, Ardakani EF, Forouzannia K
and Moshtaghian H . Effects of allopurinol and
vitamin E on renal function in patients with cardiac
coronary artery bypass grafts. Vasc. Health Risk
Manag . (2009) 5: 489-94.
(8) Garg AX, Chan MT, Cuerden MS, Devereaux
P, Abbasi SH, Hildebrand A, Lamontagne F,
Lamy A, Noiseux N and Parikh C. Effect of
methylprednisolone on acute kidney injury
in patients undergoing cardiac surgery with a
cardiopulmonary bypass pump: a randomized
controlled trial. Can. Med. Assoc. J. (2019) 191:
247-56.
(9) Park J, Lee JH, Kim KA, Lee SH, Lee YT, Kim
WS and Min J. Effects of preoperative statin on
acute kidney injury after off‐pump coronary artery
bypass grafting. Circ. J. (2019) 8: 10-3.
(10) Savluk OF, Guzelmeric F, Yavuz Y, Cevirme
D, Gurcu E, Ogus H, Orki T and 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) 32: 8-14.
(11) Bove T, Zangrillo A, Guarracino F, Alvaro G, Persi
B, Maglioni E, Galdieri N, Comis M, Caramelli
F and Pasero DC. Effect of fenoldopam on use
of renal replacement therapy among patients
with acute kidney injury after cardiac surgery: a
randomized clinical trial. JAMA (2014) 312: 2244-
53.
(12) Haase M, Haase-Fielitz A, Plass M, Kuppe
H, Hetzer R, Hannon C, Murray PT, Bailey
MJ, Bellomo R, and Bagshaw S. Prophylactic
perioperative sodium bicarbonate to prevent acute
kidney injury following open heart surgery: a
multicenter double-blinded randomized controlled
trial. PLoS Med (2013) 10: 14-26.
(13) Lomivorotov V, Kornilov I, Boboshko V, Shmyrev
V, Bondarenko I, Soynov I, Voytov A, Polyanskih
S, Strunin O, Bogachev-Prokophiev A, Landoni
G, Nigro Neto C, Oliveira Nicolau G, Saurith
Izquierdo L, Nogueira Nascimento V, Wen Z,
Renjie H, Haibo Z, Bazylev V, Evdokimov M,
Sulejmanov S, Chernogrivov A and Ponomarev
D. Effect of Intraoperative Dexamethasone on
Major Complications and Mortality Among Infants
Undergoing Cardiac Surgery: The DECISION
Randomized Clinical Trial. JAMA (2020) 323:
2485-92.
(14) Santana-Santos E, Marcusso MEF, Rodrigues AO,
de Queiroz FG, de Oliveira LB, Rodrigues ARB
and Palomo J. Strategies for prevention of acute
kidney injury in cardiac surgery: an integrative
review. Rev Bras Ter Intensiva (2014) 26: 183-92.
(15) Habibzadeh P, Mofatteh M, Ghavami S and
Roozbeh J. The potential effectiveness of
acetazolamide in the prevention of acute kidney
injury in COVID-19: A hypothesis. Eur. J.
Pharmacol. (2020) 888: 173487.
(16) Assadi F. Acetazolamide for prevention of contrastinduced nephropathy: a new use for an old drug.
Pediatr. Cardiol. (2006) 27: 238-42.
(17) Shamash J, Earl H and Souhami R. Acetazolamide
for alkalinisation of urine in patients receiving
high-dose methotrexate. Cancer Chemother.
Pharmacol. (1991) 28: 150-1.
(18) An Y, Zhang JZ, Han J, Yang Hp, Tie L, Yang
XY, Xiaokaiti Y, Pan Y and Li XJ. Hypoxiainducible factor-1α dependent pathways mediate
the renoprotective role of acetazolamide against 
79
Effect of Acetazolamide on Post-CABG Acute Kidney Injury
renal ischemia-reperfusion injury. Cell. Physiol.
Biochem. (2013) 32: 1151-66.
(19) Khwaja A. KDIGO clinical practice guidelines for
acute kidney injury. Nephron. Clinical Practice.
(2012) 120: 179-84.
(20) Olsson D, Sartipy U, Braunschweig F and
Holzmann MJ. Acute kidney injury following
coronary artery bypass surgery and long-term risk
of heart failure. Circ. Heart Fail (2013) 6: 83-90.
(21) Warren J, Mehran R, Baber U, Xu K, Giacoppo
D, Gersh BJ, Guagliumi G, Witzenbichler B,
Ohman EM and Pocock SJ. Incidence and impact
of acute kidney injury in patients with acute
coronary syndromes treated with coronary artery
bypass grafting: Insights from the harmonizing
outcomes with revascularization and stents in acute
myocardial infarction (HORIZONS-AMI) and
acute catheterization and urgent intervention triage
strategy (ACUITY) trials. Am. Heart J. (2016) 171:
40-7.
(22) Rosner MH and Okusa MD. Acute kidney injury
associated with cardiac surgery. Clin. J. Am. Soc.
Nephrol. (2006) 1: 19-32.
(23) Yang Y, Wu YX and Hu YZ. Rosuvastatin treatment
for preventing contrast-induced acute kidney injury
after cardiac catheterization: a meta-analysis of
randomized controlled trials. Medicine (2015) 94:
1226.
(24) Osman NM, Copley MP and Litterst CL.
Amelioration of cisplatin-induced nephrotoxicity
by the diuretic acetazolamide in F344 rats. Cancer
Treat. Rep. (1984) 68: 999-1004.
(25) Taki K, Oogushi K, Hirahara K, Gai X, Nagashima
F and Tozuka K. Preferential acetazolamideinduced vasodilation based on vessel size and
organ: confirmation of peripheral vasodilation with
use of colored microspheres. Angiology (2001) 52:
483-8.
(26) Kassamali R and Sica DA. Acetazolamide: a
forgotten diuretic agent. Cardiol. Rev. (2011) 19:
276-8.
(27) Horita Y, Yakabe K, Tadokoro M, Suyama N,
Hayashida K, Kawano Y, Miyazaki M, Kohno S and
Taura K. Renal circulatory effects of acetazolamide
in patients with essential hypertension. Am. J.
Hypertens. (2006) 19: 282-5.
(28) Rossert J, Rondeau E, Jondeau G, Ronco P,
Mougenot B, Kanfer A and Sraer J. TammHorsfall protein accumulation in glomeruli during
acetazolamide-induced acute renal failure. Am. J.
Nephrol. (1989) 9: 56-7.
(29) López-Menchero R, Albero M, Barrachina M
and Alvarez L. Anuric acute renal failure due to
acetazolamide. J. Investig. Med. High Impact Case
Rep. (2006) 26: 755-6.
(30) Glushien AS and Fisher E. Renal lesions
of sulfonamide type after treatment with
acetazolamide (Diamox). JAMA (1956) 160: 204-
6.
(31) Yates-Bell J. Renal colic and anuria from
acetazolamide. J. Investig. Med. High Impact Case
Rep (1958) 2: 1-5.
(32) Olivero JJ, Olivero JJ, Nguyen PT and Kagan A.
Acute kidney injury after cardiovascular surgery:
an overview. Methodist Debakey Cardiovasc. J.
(2012) 8: 31-6.
(33) Bellomo R, Auriemma S, Fabbri A, D’Onofrio
A, Katz N, McCullough P, Ricci Z, Shaw A and
Ronco C. The pathophysiology of cardiac surgeryassociated acute kidney injury (CSA-AKI). Int. J.
Artif. Organs (2008) 31: 166-78.
(34) Pavlakou P, Liakopoulos V, Eleftheriadis T, Mitsis
M and Dounousi E. Oxidative Stress and Acute
Kidney Injury in Critical Illness: Pathophysiologic
Mechanisms—Biomarkers—Interventions, and
Future Perspectives. Oxidative Med. Cell. Longev.
(2017) 2017: 6193694.
(35) Nensén O, Hansell P and Palm F. Role of carbonic
anhydrase in acute recovery following renal
ischemia reperfusion injury. PLoS One (2019) 14:
220185.
(36) Skøtt P, Hommel E, Bruun N, Arnold-Larsen S and
Parving HJS. The acute effect of acetazolamide
on glomerular filtration rate and proximal tubular
reabsorption of sodium and water in normal man.
Scand. J.Clin .Lab. Invest. (1989) 49: 583-7.
(37) Halliwell B and Gutteridge JM. Role of free
radicals and catalytic metal ions in human disease:
an overview. Meth. Enzymol. (1990) 186: 1-85.
(38) Sharbaf FG, Farhangi H and Assadi F. Prevention
of chemotherapy-induced nephrotoxicity in
children with cancer. Int. J. Prev. Med. (2017) 8:
76.
(39) Mittal M, Siddiqui MR, Tran K, Reddy SP and
Malik AB. Reactive oxygen species in inflammation
and tissue injury. Antioxid. Redox Signal. (2014)
20: 1126-67.
(40) Schmickl CN, Owens RL, Orr JE, Edwards BA
and Malhotra A. Side effects of acetazolamide: a
systematic review and meta-analysis assessing
overall risk and dose dependence. BMJ Open
Respir Res. (2020) 7: 557.