Effect of pentoxifylline on preventing acute kidney injury after cardiac surgery by measuring urinary neutrophil gelatinase - associated lipocalin.
BACKGROUND
Based on Acute Kidney Injury Network (AKIN) criteria, we considered acute kidney injury (AKI) as an absolute increase in the serum creatinine (sCr) level of more than or equal to 0.3 mg/dl or 50%. The introduction of Urinary neutrophil gelatinase-associated lipocalin (UNGAL) has conferred earlier diagnosis of AKI. Pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor, can suppress the production of some factors of inflammatory response and presumably prevent AKI. We examined the PTX on the development of AKI in cardiac surgery patients by measuring the levels of UNGAL.


METHODS
We performed a double blind randomized clinical trial, enrolling 28 consecutive patients undergoing elective coronary artery bypass graft (CABG) surgery. Patients were divided into two groups, one to receive PTX 5 mg/kg intravenous bolus injection, followed by 1.5 mg/kg/h continuous intravenous infusion until 3 hours after cessation of CPB and the other group received placebo. UNGAL was measured before, 3 and 24 hours after surgery. In addition serum creatinine was measured before and 24, 48, 72 and 96 hours after surgery and C-reactive protein (CRP) only 24 hours postoperatively.


RESULTS
Both groups did not differ in demographic and baseline characteristics. 12 patients developed AKI 48 hours after surgery; 5 of them were in the intervention group and 7 in the control group (p= 0.445). There was an increase of UNGAL in both groups postoperatively, although not significant. Mean sCr was significantly increased in the control group at 24 and 48 hours after surgery (24-h mean: 0.79 ± 0.18 mg/dl vs. 1.03 ± 0.43 mg/dl, P value = 0.02; 48-h mean: 1.17 ± 0.24 mg/dl vs. 0.98 ± 0.20 mg/dl, P value = 0.03, respectively). PTX had a positive effect in preventing AKI reflecting in changes in sCr, and the increase of UNGAL was consistent with the emergence of AKI (Pearson's correlation = 0.30).


CONCLUSIONS
Our study demonstrates a weak correlation between UNGAL and sCr after cardiac surgery. The rise of UNGAL in these patients may be reduced by administration of PTX although we did not show significance. PTX could reduce the occurrence of AKI as determined by attenuation of sCr rise without causing hemodynamic instability or increased bleeding. Overall, we suggest future studies with larger sample sizes to elucidate this effect and determine the different aspects of administrating PTX.


BACKGROUND
ISRCTN: IRCT138807302622N1.
Department of Anesthesiology and Critical Care, Tehran Heart Center, Tehran University of Medical Sciences, Iran. kbarkhordari@sina.tums.ac.ir
Khosro
K
Barkhordari
Abbasali
A
Karimi
Akbar
A
Shafiee
Hasan
H
Soltaninia
Mohammad Reza
MR
Khatami
Kiomars
K
Abbasi
Fardin
F
Yousefshahi
Babak
B
Haghighat
Virginia
V
Brown
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003327:Coronary Disease / Q000601:surgery / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage*; D011183:Postoperative Complications; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012189:Retrospective Studies; D016896:Treatment Outcome
D000209:Acute-Phase Proteins; D015415:Biomarkers; D016166:Free Radical Scavengers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D010431:Pentoxifylline
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