Iranian Journal of Medical Sciences

Document Type : Original Article(s)

Authors

1 Department of Critical Care Medicine, Emam Hossein Medical and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Prevention of Cardiovascular Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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

Abstract

Background: Multiple trauma can cause an increase in creatine phosphokinase (CPK) and subsequently rhabdomyolysis and acute kidney injury (AKI). This study was designed to evaluate the effect of vitamin D3 on the serum CPK level and the incidence of rhabdomyolysis-induced AKI in patients with multiple trauma.
Methods: Patients with serum CPK levels <1000 IU/L were followed as the control 1 group. Subjects with serum CPK levels ≥1000 IU/L were randomly allocated to the control 2 or intervention group at Imam Hossein Medical Center, Tehran, Iran in 2020. Patients in the intervention group received a single dose of vitamin D3 (300,000 units) on the recruitment day. The serum level of CPK was recorded every 3 days for 14 days. Parametric and non-parametric tests were used to compare the CPK values between groups.
Results: Forty-six patients, consisting of 16, 15, and 15 in control 1, control 2, and intervention arms of the study were recruited, respectively. Unlike control groups, the significant steadily decreasing trend was seen only in the intervention group (P<0.001). This significant decrease in the intervention arm was observed on days 5 to 7 (P=0.001) and on days 8 to 10 (P<0.001) compared to the baseline.
Patients in the intervention group had a lower number of AKI or need for dialysis (P=0.869 and P=0.670 for AKI and dialysis, respectively) than control group 2, although the differences were not significant. 
Conclusion: The current study revealed that vitamin D3, could prevent the increasing trend of CPK during the first days and accelerate the normalization of CPK in patients with elevated CPK due to multiple trauma.
Trial registration number: IRCT20120703010178N23.

Keywords

  1. Kroupa J. Definition of “polytrauma” and “polytraumatism”. Acta Chir Orthop Traumatol Cech. 1990;57:347-60. PubMed PMID: 2239047.
  2. Mondello S, Cantrell A, Italiano D, Fodale V, Mondello P, Ang D. Complications of trauma patients admitted to the ICU in level I academic trauma centers in the United States. Biomed Res Int. 2014;2014:473419. doi: 10.1155/2014/473419. PubMed PMID: 24995300; PubMed Central PMCID: PMCPMC4065752.
  3. Săndesc D. Oxidative stress in the critically ill polytrauma patient. The Journal of Critical Care Medicine. 2015;1:81-2. doi: 10.1515/jccm-2015-0013.
  4. Rogobete AF, Sandesc D, Papurica M, Stoicescu ER, Popovici SE, Bratu LM, et al. The influence of metabolic imbalances and oxidative stress on the outcome of critically ill polytrauma patients: a review. Burns Trauma. 2017;5:8. doi: 10.1186/s41038-017-0073-0. PubMed PMID: 28286784; PubMed Central PMCID: PMCPMC5341432.
  5. Motoyama T, Okamoto K, Kukita I, Hamaguchi M, Kinoshita Y, Ogawa H. Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome. Crit Care Med. 2003;31:1048-52. doi: 10.1097/01.CCM.0000055371.27268.36. PubMed PMID: 12682471.
  6. Grivei A, Giuliani KTK, Wang X, Ungerer J, Francis L, Hepburn K, et al. Oxidative stress and inflammasome activation in human rhabdomyolysis-induced acute kidney injury. Free Radic Biol Med. 2020;160:690-5. doi: 10.1016/j.freeradbiomed.2020.09.011. PubMed PMID: 32942024.
  7. Paterna S, Di Gaudio F, La Rocca V, Balistreri F, Greco M, Torres D, et al. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure. Adv Ther. 2015;32:971-82. doi: 10.1007/s12325-015-0254-9. PubMed PMID: 26521190; PubMed Central PMCID: PMCPMC4635178.
  8. Lima RS, da Silva Junior GB, Liborio AB, Daher Ede F. Acute kidney injury due to rhabdomyolysis. Saudi J Kidney Dis Transpl. 2008;19:721-9. PubMed PMID: 18711286.
  9. Dennis JM, Witting PK. Protective Role for Antioxidants in Acute Kidney Disease. Nutrients. 2017;9. doi: 10.3390/nu9070718. PubMed PMID: 28686196; PubMed Central PMCID: PMCPMC5537833.
  10. Lucas GNC, Leitao ACC, Alencar RL, Xavier RMF, Daher EF, Silva Junior GBD. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs. J Bras Nefrol. 2019;41:124-30. doi: 10.1590/2175-8239-JBN-2018-0107. PubMed PMID: 30281062; PubMed Central PMCID: PMCPMC6534025.
  11. Sistanizad M, Kouchek M, Miri M, Salarian S, Shojaei S, Vasegh FM, et al. High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients-A randomized, double-blind clinical trial. European Journal of Integrative Medicine. 2021;42:101271. doi: 10.1016/j.eujim.2020.101271.
  12. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014;7:69-87. doi: 10.2147/JIR.S63898. PubMed PMID: 24971027; PubMed Central PMCID: PMCPMC4070857.
  13. Kim DH, Meza CA, Clarke H, Kim JS, Hickner RC. Vitamin D and Endothelial Function. Nutrients. 2020;12. doi: 10.3390/nu12020575. PubMed PMID: 32098418; PubMed Central PMCID: PMCPMC7071424.
  14. Liu W, Zhang L, Xu HJ, Li Y, Hu CM, Yang JY, et al. The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis. Int J Mol Sci. 2018;19. doi: 10.3390/ijms19092736. PubMed PMID: 30216977; PubMed Central PMCID: PMCPMC6164284.
  15. Gembillo G, Siligato R, Amatruda M, Conti G, Santoro D. Vitamin D and Glomerulonephritis. Medicina (Kaunas). 2021;57. doi: 10.3390/medicina57020186. PubMed PMID: 33671780; PubMed Central PMCID: PMCPMC7926883.
  16. Koroshi A, Idrizi A. Renoprotective effects of Vitamin D and renin-angiotensin system. Hippokratia. 2011;15:308-11. PubMed PMID: 24391410; PubMed Central PMCID: PMCPMC3876844.
  17. Kim CS, Kim SW. Vitamin D and chronic kidney disease. Korean J Intern Med. 2014;29:416-27. doi: 10.3904/kjim.2014.29.4.416. PubMed PMID: 25045287; PubMed Central PMCID: PMCPMC4101586.
  18. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31. doi: 10.1186/cc5713. PubMed PMID: 17331245; PubMed Central PMCID: PMCPMC2206446.
  19. Nugent C, Roche K, Wilson S, Fitzgibbon M, Griffin D, Nichaidhin N, et al. The effect of intramuscular vitamin D (cholecalciferol) on serum 25OH vitamin D levels in older female acute hospital admissions. Ir J Med Sci. 2010;179:57-61. doi: 10.1007/s11845-009-0410-9. PubMed PMID: 19714394.
  20. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-29. PubMed PMID: 3928249.
  21. Assanangkornchai N, Akaraborworn O, Kongkamol C, Kaewsaengrueang K. Characteristics of Creatine Kinase Elevation in Trauma Patients and Predictors of Acute Kidney Injury. J Acute Med. 2017;7:54-60. doi: 10.6705/j.jacme.2017.0702.002. PubMed PMID: 32995172; PubMed Central PMCID: PMCPMC7517910.
  22. Glueck CJ, Conrad B. Severe vitamin d deficiency, myopathy, and rhabdomyolysis. N Am J Med Sci. 2013;5:494-5. doi: 10.4103/1947-2714.117325. PubMed PMID: 24083227; PubMed Central PMCID: PMCPMC3784929.
  23. Rasheed K, Sethi P, Bixby E. Severe vitamin d deficiency induced myopathy associated with rhabydomyolysis. N Am J Med Sci. 2013;5:334-6. doi: 10.4103/1947-2714.112491. PubMed PMID: 23814767; PubMed Central PMCID: PMCPMC3690793.
  24. Gunton JE, Girgis CM. Vitamin D and muscle. Bone Rep. 2018;8:163-7. doi: 10.1016/j.bonr.2018.04.004. PubMed PMID: 29963601; PubMed Central PMCID: PMCPMC6021354.
  25. Montenegro KR, Cruzat V, Carlessi R, Newsholme P. Mechanisms of vitamin D action in skeletal muscle. Nutr Res Rev. 2019;32:192-204. doi: 10.1017/S0954422419000064. PubMed PMID: 31203824.
  26. Graidis S, Papavramidis TS, Papaioannou M. Vitamin D and Acute Kidney Injury: A Two-Way Causality Relation and a Predictive, Prognostic, and Therapeutic Role of Vitamin D. Front Nutr. 2020;7:630951. doi: 10.3389/fnut.2020.630951. PubMed PMID: 33748167; PubMed Central PMCID: PMCPMC7969500.
  27. Jiang S, Huang L, Zhang W, Zhang H. Vitamin D/VDR in Acute Kidney Injury: A Potential Therapeutic Target. Curr Med Chem. 2021;28:3865-76. doi: 10.2174/0929867327666201118155625. PubMed PMID: 33213307.
  28. Panizo N, Rubio-Navarro A, Amaro-Villalobos JM, Egido J, Moreno JA. Molecular Mechanisms and Novel Therapeutic Approaches to Rhabdomyolysis-Induced Acute Kidney Injury. Kidney Blood Press Res. 2015;40:520-32. doi: 10.1159/000368528. PubMed PMID: 26512883.
  29. Reis NG, Francescato HDC, de Almeida LF, Silva C, Costa RS, Coimbra TM. Protective effect of calcitriol on rhabdomyolysis-induced acute kidney injury in rats. Sci Rep. 2019;9:7090. doi: 10.1038/s41598-019-43564-1. PubMed PMID: 31068635; PubMed Central PMCID: PMCPMC6506495.