Introduction
Acute kidney injury (AKI) refers to a sudden loss of kidney function with the increase of serum creatinine level (a marker of kidney function) and reduction of urinary output or oliguria (a marker of urine production) and lasts 7 days [1]. The risk factors of AKI include age, history of kidney disease, left ventricular ejection fraction <35%, cardiac index <1.7 L/min/m2, hypertension, peripheral vascular disease, diabetes mellitus, emergency surgery, and type of surgery [12, 13]. Since orthopedic surgeries have increased in recent years and due to the effect of these surgeries on the occurrence of AKI, we aim to determine the frequency and risk factors of AKI in patients undergoing major orthopedic surgery.
Methods
In this analytical cross-sectional study, 180 patients undergoing major orthopedic surgery in Rasht, Iran participated. The sample size was determined based on the study of Hennrikus et al. [16] considering the frequency of AKI in orthopedic surgeries. Patients were examined in terms of the frequency of AKI (sudden renal failure with at least one of the following characteristics: an increase of at least 0.3 mg/dL in serum creatinine level, 50% increase in serum creatinine level compared to the baseline level within 8-24 hours, urinary output <0.5 cc/kg/h for more than 6 hours) after surgery and related risk factors were investigated. Major orthopedic surgery refers to a surgery that takes more than one hour or the patient loses about 500 cc of blood. Patients who had a history of chronic kidney disease, abnormal creatinine level before surgery (>1.5), dialysis, or incomplete medical records were excluded from the study. For sampling, gradual sampling method was used.
Results
Of 180 patients, 131 (72.8%) were male. Twenty patients (11.11%) had AKI after major orthopedic surgery, of whom 14 (70%) were male. Table 1 shows the results of comparing demographic/clinical factors in two groups of with and without AKI after major orthopedic surgery.


The use of non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) had no significant relationship with the occurrence of AKI (P>0.05). Regarding the underlying diseases, the results showed the significant relationship of the history of heart disease, diabetes, and kidney disease with AKI. However, no significant relationship between high blood pressure and AKI was reported (P=0.195). According to the results of linear regression analysis, the creatinine level before surgery had a significant relationship with the creatinine level after surgery, such that with the increase of one unit in preoperative creatinine level, the postoperative creatinine level increased by 0.3 (B=0.29, P=0.024). 
Discussion 
The AKI is associated with a decrease in glomerular filtration rate and can lead to chronic kidney disease or end-stage renal disease. Its prevalence is increasing rapidly and it has a long-term impact on health. The treatment costs of this injury are very high which imposes a heavy burden on the healthcare system [17]. According to the results of this study, the incidence of AKI after major orthopedic surgeries in Rasht city was 11.11%. In a study conducted by Jin Lee et al. in 2021, on the risk factors of AKI after hip and knee joint replacement surgeries, 3.7% of 351 patients had AKI [14]. In other studies [18, 19], the prevalence of AKI after orthopedic surgery was in the ranges of 0.55-1.8%. The reported incidence of AKI in these studies was lower than in our study. The higher rate of AKI in our study is probably because we used the AKI network (AKIN) criteria to diagnose AKI, which has a higher sensitivity than other systems; this criteria was used before the appearance of clinical symptoms of AKI. Farrow et al. [23] in 2022 investigated the prevalence of AKI in patients who underwent lower limb arthroplasty. They reported that three factors of diabetes, chronic kidney disease and male gender had a significant relationship with AKI. In our study, AKI incidence had also a significant relationship with diabetes. The incidence AKI after major orthopedic surgeries was higher in our study compared to that in previous studies. In this study, preoperative creatinine level, old age, diabetes, and kidney disease had a significant relationship with the incidence of AKI after surgery. Tt is possible to prevent the occurrence of postoperative AKI by paying attention to these risk factors and more careful monitoring of patients at risk before, during and after major orthopedic surgery.

Ethical Considerations
Compliance with ethical guidelines
The study was approved by the Ethical Committee of Guilan University of Medical Sciences (IR.GUMS.REC.1401.130) and complied with the rules delineated in the Helsinki Declaration

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions
Conceptualization and design of the study: Ali Ashraf, Pegah Aghajanzadeh and Niloofar Hamedi; Acquisition, analysis and interpretation of data and statistical analysis: Ali Ashraf; Drafting of the manuscript: Ali Ashraf, Niloofar Hamedi, Pegah Aghajanzadeh and Maliheh Akbarpour; Critical revision of the manuscript for important intellectual content: Ali Ashraf and Maliheh Akbarpour.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors would like to thank the patients for taking part in this study.


References

1. Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nature Reviews. Disease Primers. 2021; 7(1):52. [DOI:10.1038/s41572-021-00284-z] [PMID]
2. Barasch J, Zager R, Bonventre JV. Acute kidney injury: A problem of definition. Lancet. 2017; 389(10071):779-81. [DOI:10.1016/S0140-6736(17)30543-3] [PMID]
3. Silver SA, Long J, Zheng Y, Chertow GM. Cost of acute kidney injury in hospitalized patients. Journal of Hospital Medicine. 2017; 12(2):70-6. [DOI:10.12788/jhm.2683] [PMID]
4. Riffaut N, Moranne O, Hertig A, Hannedouche T, Couchoud C. Outcomes of acute kidney injury depend on initial clinical features: A national French cohort study. Nephrology, Dialysis, Transplantation. 2018; 33(12):2218-27. [DOI:10.1093/ndt/gfy137] [PMID]
5. Sehgal V, Bajwa SJ, Sehgal R, Eagan J, Reddy P, Lesko SM. Predictors of acute kidney injury in geriatric patients undergoing total knee replacement surgery. International Journal of Endocrinology and Metabolism. 2014; 12(3):e16713. [DOI:10.5812/ijem.16713] [PMID]
6. Thakar CV. Perioperative acute kidney injury. Advances in chronic kidney disease. 2013; 20(1):67-75. [DOI:10.1053/j.ackd.2012.10.003] [PMID]
7. Dubrovskaya Y, Tejada R, Bosco J 3rd, Stachel A, Chen D, Feng M, et al. Single high dose gentamicin for perioperative prophylaxis in orthopedic surgery: Evaluation of nephrotoxicity. SAGE Open Medicine. 2015; 3:2050312115612803. [DOI:10.1177/2050312115612803] [PMID] [PMCID]
8. Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: The PrevAKI randomized controlled trial. Intensive Care Medicine. 2017; 43(11):1551-61. [DOI:10.1007/s00134-017-4735-y] [PMID] [PMCID]
9. Göcze I, Jauch D, Götz M, Kennedy P, Jung B, Zeman F, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: The prospective randomized bigpak study. Annals of Surgery. 2018; 267(6):1013-20. [DOI:10.1097/SLA.0000000000002485] [PMID]
10. Selby NM, Casula A, Lamming L, Stoves J, Samarasinghe Y, Lewington AJ, et al. An organizational-level program of intervention for aki: A pragmatic stepped wedge cluster randomized trial. Journal of the American Society of Nephrology. 2019; 30(3):505-15. [DOI:10.1681/ASN.2018090886] [PMID] [PMCID]
11. Kashani K, Rosner MH, Haase M, Lewington AJP, O'Donoghue DJ, Wilson FP, et al. Quality improvement goals for acute kidney injury. Clinical Journal of the American Society of Nephrology. 2019; 14(6):941-53. [DOI:10.2215/CJN.01250119] [PMID] [PMCID]
12. Kateros K, Doulgerakis C, Galanakos SP, Sakellariou VI, Papadakis SA, Macheras GA. Analysis of kidney dysfunction in orthopaedic patients. BMC Nephrology. 2012; 13:101.[DOI:10.1186/1471-2369-13-101] [PMID] [PMCID]
13. Jafari SM, Huang R, Joshi A, Parvizi J, Hozack WJ. Renal impairment following total joint arthroplasty: Who is at risk? The Journal of Arthroplasty. 2010; 25(6 Suppl):49-53. [DOI:10.1016/j.arth.2010.04.008] [PMID]
14. Lee YJ, Park BS, Park S, Park JH, Kim IH, Ko J, et al. Analysis of the risk factors of acute kidney injury after total hip or knee replacement surgery. Yeungnam University Journal of Medicine. 2021; 38(2):136-41. [DOI:10.12701/yujm.2020.00542] [PMID] [PMCID]
15. Monfared A, Khosravi M, Orang poor R, Moosavian Roshan zamir S, Aghajani Nargesi D. Reasons of chronic renal failure in hemodialysis patients in guilan province. Journal of Guilan University of Medical Science. 2003; 12(46):76-83. [Link]
16. Hennrikus MT, Hennrikus WP, Lehman E, Hennrikus EF. Obesity, angiotensin-blocking drugs, and acute kidney injury in orthopedic surgery. Orthopedics. 2021; 44(2):e253-8. [DOI:10.3928/01477447-20201216-08] [PMID]
17. Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, et al. Global epidemiology and outcomes of acute kidney injury. Nature Reviews Nephrology. 2018; 14(10):607-25. [DOI:10.1038/s41581-018-0052-0] [PMID]
18. Bell S, Davey P, Nathwani D, Marwick C, Vadiveloo T, Sneddon J, et al. Risk of AKI with gentamicin as surgical prophylaxis. Journal of the American Society of Nephrology. 2014; 25(11):2625-32. [DOI:10.1681/ASN.2014010035] [PMID] [PMCID]
19. Warth LC, Noiseux NO, Hogue MH, Klaassen AL, Liu SS, Callaghan JJ. Risk of acute kidney injury after primary and revision total hip arthroplasty and total knee arthroplasty using a multimodal approach to perioperative pain control including ketorolac and celecoxib. The Journal of Arthroplasty. 2016; 31(1):253-5. [DOI:10.1016/j.arth.2015.08.012] [PMID]
20. Raimann JG, Riella MC, Levin NW. International society of nephrology's 0by25 initiative (zero preventable deaths from acute kidney injury by 2025): Focus on diagnosis of acute kidney injury in low-income countries. Clinical Kidney Journal. 2018; 11(1):12-9. [DOI:10.1093/ckj/sfw134] [PMID] [PMCID]
21. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice. 2012; 120(4):c179-84. [DOI:10.1159/000339789] [PMID]
22. Hancı V, Özbilgin Ş, Başçı O, Ömür D, Boztaş N. Acute kidney injury after major orthopedic surgery: A retrospective study of frequency and related risk factors. Acta Orthopaedica et Traumatologica Turcica. 2022; 56(4):289-95. [DOI:10.5152/j.aott.2022.22048] [PMID] [PMCID]
23. Farrow L, Smillie S, Duncumb J, Chan B, Cranfield K, Ashcroft G, et al. Acute kidney injury in patients undergoing elective primary lower limb arthroplasty. European Journal of Orthopaedic Surgery & Traumatology. 2022; 32(4):661-5. [DOI:10.1007/s00590-021-03024-x] [PMID] [PMCID]
24. Kheirkhah J, Ahmadnia Z, Salari A, Dadkhah H, Modallalkar SS, Hasandokht T. Acute kidney injury after cardiac surgery in the north of Iran. Journal of Nephropathology. 2022; 11(1):e5. [DOI:10.34172/jnp.2022.05]
25. Amini S, Najafi MN, Karrari SP, Mashhadi ME, Mirzaei S, Tashnizi MA, et al. Risk factors and outcome of acute kidney injury after isolated cabg surgery: A prospective cohort study. Brazilian Journal of Cardiovascular Surgery. 2019; 34(1):70-5. [DOI:10.21470/1678-9741-2017-0209] [PMID] [PMCID]