Preliminary clinical study of the alpha-tocopherol to reduce colistin nephrotoxicity among hospitalized patients
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Abstract
Background: Colistin is an antibiotic used to treat multidrug-resistant gram-negative bacterial infections. Colistin causes serious nephrotoxicity by incidence from 50-70%. The main mechanism of colistin-associated nephrotoxicity is tubular injury via oxidative inflammatory pathway. Alpha-tocopherol exhibits strong antioxidant effects, low toxicity, rare side effects, and low cost. This study aimed to investigate the protective effects of alpha-tocopherol on colistin-induced nephrotoxicity.
Methods: This study constituted an open-label, randomized controlled trial of hospitalized patients receiving colistin in Bhumibol Adulyadej Hospital from July 2019 to February 2020. All patients received the standard dose of colistin, and were randomized in 2 groups, the alpha-tocopherol group, receiving once daily oral alpha-tocopherol 350 mg, and the control group, receiving standard care. The primary outcome was the incidence of acute kidney injury within 14 days. We assessed using blood tests for serum creatinine days 0, 2, 5, 7, 9, 11, 13 and serum neutrophil gelatinase-associated lipocalin (NGAL) day 7.
Results: The present randomized controlled study was conducted among 23 patients. Of these, 11 patients were in the alpha-tocopherol group, and 12 patients received standard care. The baseline characteristics, clinical features, and concomitant treatments of patients in both groups were comparable, except the baseline serum creatinine level in the alpha-tocopherol group was higher than that in the control group. The incidence of acute kidney injury was 45.4% (5/11) and 75.0% (9/12) in the alpha-tocopherol and control group, respectively (p-value=0.214). Mean serum NGAL levels on the 7th day were 225 ng/mL and 361 ng/mL in the alpha-tocopherol and control group, respectively (p-value = 0.465).
Conclusion: The result of our study could not demonstrate any difference regarding incidence of colistin nephrotoxicity between both groups. The reason might be the low power of the study due to insufficient sample recruitment. A larger study is needed to confirm the potential protective effect of alpha-tocopherol to prevent colistin-induced acute kidney injury (Registered at Thai Clinical Trial Registry under registration no.20190730001).
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References
Miano TA, Lautenbach E, Wilson FP, Guo W, Borovskiy Y, Hennessy S. Attributable risk and time course of colistin-associated acute kidney injury. Clin J Am Soc Nephrol. 2018; 13(4):542–50.
McKenna M. Antibiotic resistance: The last resort. Nat News. 2013; 499(7459):394.
Dalfino L, Puntillo F, Ondok MJM, Mosca A, Monno R, Coppolecchia S, et al. Colistin-associated acute kidney injury in severely Ill Patients: A step toward a better renal care? A prospective cohort study. Clin Infect Dis. 2015; 61(12):1771–7.
Sirijatuphat R, Limmahakhun S, Sirivatanauksorn V, Nation RL, Li J, Thamlikitkul V. Preliminary clinical study of the effect of ascorbic acid on colistin-as sociated nephrotoxicity. Antimicrob Agents Chemother. 2015; 59(6):3224–32.
Ordooei Javan A, Shokouhi S, Sahraei Z. A review on colistin nephrotoxicity. Eur J Clin Pharmacol. 2015; 71(7):801–10.
Ozkan G, Ulusoy S, Orem A, Alkanat M, Mungan S, Yulug E, et al. How does colistin-induced nephropathy develop and can it be treated? Antimicrob Agents Chemother. 2013; 57(8):3463–9.
Ceylan B, Ozansoy M, Kılıç Ü, Yozgat Y, Ercan Ç, Yıldız P, et al. N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS, and MMP3 protein expressions. Ren Fail. 2018; 40(1):423–34.
Shields RK, Anand R, Clarke LG, Paronish JA, Weirich M, Perone H, et al. Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria. Burdmann EA, editor. PLOS ONE. 2017; 12(3):e0173286.
ณิชาภา ไทบ้านก้วย, อนันต์ เชื้อสุวรรณ. Incidence and Risk factor of acute kidney injury in patient receiving colistin in Bhumibol Adulyadej Hospital, 2557 (Unpublished)).
Liu P, Feng Y, Wang Y, Zhou Y, Zhao L. Protective effect of vitamin E against acute kidney injury. Liu F, Lee D-H, Lagoa R, Kumar S, editors. Biomed Mater Eng. 2015; 26(s1):S2133–44.
Kadkhodaee M, Khastar H, Faghihi M, Ghaznavi R, Zahmatkesh M. Effects of co-supplementation of vitamins E and C on gentamicin-induced nephrotoxicity in rat: Vitamins E and C prevent gentamicin-induced nephrotoxicity. Exp Physiol. 2005; 90(4):571–6.
Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad M. Short-term high-dose vitamin E to prevent contrast medium–induced acute kidney injury in patients with chronic kidney disease undergoing elective coronary angiography: A randomized placebo-controlled trial. J Am Heart Assoc 2016;5:e002919.
Cho MH, Kim SN, Park HW, Chung S, Kim KS. Could Vitamin E prevent contrast-induced acute kidney injury? A systematic review and meta-analysis. J Korean Med Sci. 2017;32(9):1468.
Arimura Y, Yano T, Hirano M, Sakamoto Y, Egashira N, Oishi R. Mitochondrial superoxide production contributes to vancomycin-induced renal tubular cell apoptosis. Free Radic Biol Med. 2012; 52(9):1865–73.
Nowak G, Bakajsova D, Hayes C, Hauer-Jensen M, Compadre CM.-tocotrienol protects against mitochondrial dysfunction and renal cell death. J Pharmacol Exp Ther. 2012; 340(2):330–8.
Ajith TA, Abhishek G, Roshny D, Sudheesh NP. Co-supplementation of single and multi doses of vitamins C and E ameliorates cisplatin-induced acute renal failure in mice. Exp Toxicol Pathol. 2009; 61(6):565–71.
Koga H, Hagiwara S, Mei H, Hiraoka N, Kusaka J, Goto K, et al. The Vitamin E derivative, eseros-GS, attenuates renal ischemia-reperfusion injury in rats. J Surg Res. 2012; 176(1):220–5.
Kongkham S, Sriwong S, Adis Tasanarong. Protective effect of alpha tocopherol on contrast-induced nephropathy in rats. Nefrol 2013. 33(1):116–23.
Siddiqui S, Ahsan H, Khan MR, Siddiqui WA. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF- expression. Toxicol Appl Pharmacol. 2013; 273(2):314–24.
Bahadoran H, Naghii M, Mofid M, Asadi M, Ahmadi K, Sarveazad A. Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat. Endocr Regul. 2016; 50(4):194–206.
Ghlissi Z, Hakim A, Mnif H, Kallel R, Zeghal K, Boudawara T, et al. Effect of vitamin E on reversibility of renal function following discontinuation of colistin in rats: Histological and biochemical investigations. Saudi J Kidney Dis Transplant. 2018; 29(1):10.
Bader Z, Waheed A, Bakhtiar S, Khan IM. Alpha-to copherol ameliorates nephrotoxicity associated with the use of colistin in rabbits. Pak J Pharm Sci. 2018;6.
Tasanarong A, Piyayotai D, Thitiarchakul S. Protection of Radiocontrast Induced Nephropathy by Vitamin E (Alpha Tocopherol): A Randomized Controlled Pilot Study. 2009;92(10):10.
Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of - and -tocopherol to prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures. Nephrol Dial Transplant. 2013; 28(2):337–44.