Emergency. 2018; 6 (1): e30 OR I G I N A L RE S E A RC H Epidemiology and Outcome of Patients with Acute Kidney Injury in Emergency Department; a Cross-Sectional Study Saeed Safari1, Behrouz Hashemi1, Mohammad Mehdi Forouzanfar1, Mehrnoush Shahhoseini1, Meysam Heidari1∗ 1. Emergency Department, Shohadaye Tajrish Hospital, Shahid Beheshti University Of Medical Sciences, Tehran, Iran. Received: April 2018; Accepted: May 2018; Published online: 5 May 2018 Abstract: Introduction: Elimination of preventable deaths due to acute kidney injury (AKI) in low-income countries by 2025 is an important healthcare goal at the international level. The present study was designed with the aim of evaluating the prevalence and outcome of AKI in patients presenting to emergency department. Methods: The present cross-sectional, retrospective study was performed on patients that presented to the emergency depart- ments of 3 major teaching hospitals, Tehran, Iran, between 2005 and 2015 and were diagnosed with AKI. Patient selection was done using consecutive sampling and required data for this study was extracted by referring to the medical profiles of the patients and filling out a checklist designed for the study. Results: 770 AKI patients with the mean age of 62.72 ± 19.79 (1 – 99) years were evaluation (59.1% male). 690 (89.61%) cases of AKI causes were pre-renal or renal. Among the pre-renal causes, 74 (73.3%) cases were due to different types of shock (p < 0.001). The most common etiologic causes of AKI in pre-renal group were hypotension (57.3%) and renal vascular in- sufficiency (31.6%). In addition, regarding the renal types, rhabdomyolysis (35.0%), medication (17.5%) and chemotherapy (15.3%) and in post-renal types, kidney stone (34.5%) were the most common etiologic causes. 327 (42.5%) patients needed dialysis and 169 (21.9%) patients died. Sex (p = 0.001), age over 60 years (p = 0.001), blood urea nitrogen level (p < 0.001), hyperkalemia (p < 0.001), metabolic acidosis (p < 0.001), cause of failure (p = 0.001), and type of failure (p = 0.009) were independent risk factors of mortality. Conclusion: The total preva- lence of AKI in emergency department was 315 for each 1000000 population and preventable mortality rate due to AKI was estimated to be 28.2 cases in each 1000000 population. The most important preventable AKI causes in the pre-renal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. Keywords: Acute kidney injury; outcome assessment (health care); prevalence; epidemiology; renal insufficiency © Copyright (2018) Shahid Beheshti University of Medical Sciences Cite this article as: Safari S, Hashemi B, Forouzanfar M, Shahhoseini M, Heidari M. Epidemiology and Outcome of Patients with Acute Kidney Injury in Emergency Department; a Cross-Sectional Study. Emergency. 2018; 6(1): e30. 1. Introduction A cute kidney injury (AKI), which was called acute renal failure in the past, is defined as sudden failure and in- efficiency of the kidney (1). This disease is one of the most important causes of mortality in hospitalized patients and with aging of the population and based on new defini- tions, the number of those affected with it has increased (2- 5). Annual prevalence of patients with AKI in need of one of the replacement methods has been reported to be about 200 ∗Corresponding Author: Meysam Heidari; Emergency Department, Shoha- daye Tajrish Hospital,Shahrdari Avenue, Tajrish Square, Tehran, Iran. Tel: +989121778121 Email: dr.meysamheydari@yahoo.com to 300 cases in 1 million population (6, 7). The causes of AKI are different based on various geographical regions and there is a significant difference in its prevalence between develop- ing and developed countries (8). Most affected population is 60 – 79 year old men and common comorbidities in this group of patients include surgery, diabetes, pneumonia, car- diac failure, stroke, and history of chronic kidney disease (9). Currently, the universal policy and the International Society of Nephrology (ISN) policy are concentrated on elimination of preventable deaths due to AKI in low-income countries by 2025 (10). For effective planning regarding reduction of preventable mortalities resulting from AKI there is a need for sufficient data regarding the epidemiologic pattern of this disease in each country. Various reports have been published in this This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com S. Safari et al. 2 regard until now but most studies have been restricted to cases after surgery or in the intensive care unit (ICU) and have somehow covered the AKI cases initiated in the hospital (11, 12). Therefore, the present study was done with the aim of evaluating the prevalence and outcome of AKI in patients presenting to emergency department as a sample of community acquired cases. 2. Methods 2.1. Study design and setting The present cross-sectional retrospective study was per- formed on patients that presented to the emergency depart- ments of teaching hospitals of Shahid Beheshti University of Medical Sciences (Imam Hossein, Loghmane Hakim and Shohadaye Tajrish), Tehran, Iran, between 2005 and 2015 and were diagnosed with AKI. These 3 hospitals are major hos- pitals and referral centers and bear the treatment burden of about one third of the patients in Tehran and its suburbs with a population of about 14 million people. Protocol of the study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences and the researchers adhered to confidentiality of patients’ data and the recommendations in the declaration of Helsinki throughout the study. 2.2. Participants All the patients who were hospitalized in the emergency de- partments of the mentioned hospitals during the studied years were evaluated via consecutive sampling. Patients who had kidney transplants or were under treatment with one of the renal replacement therapy (RRT) methods including blood or peritoneal dialysis were excluded from the study. In addition, patients with a missing data regarding the con- firmed diagnosis or the etiologic causes of AKI were also ex- cluded from the study. No age or sex limitations were consid- ered for the present study. 2.3. Data gathering Data required for the present study was gathered by refer- ring to the medical profiles of the patients and by filling out a checklist designed for the study. For this purpose, by re- ferring to the medical document registry center of the men- tioned hospitals, the list of patients who had been hospi- talized via the emergency department with diagnosis of AKI alone or along with other diagnoses were extracted. Then, using the identification number of each patient, their clini- cal profile was extracted from the archive and a trained se- nior emergency medicine resident studied the profile and ex- tracted the data by consulting an emergency medicine spe- cialist. The checklist used in the present study included demo- Table 1: Baseline characteristics of the studied patients Variable Frequency (%) Sex Male 455 (59.1) Female 315 (40.9) Age (year) 1 – 19.9 17 (2.2) 20 – 39.9 100 (13.0) 40 – 59.9 176 (22.9) ≤ 60 47 (61.9) Underlying illness Hypertension 352 (45.7) Diabetes 126 (16.4) Cardiovascular disease 51 (6.6) Malignancy 44 (5.7) Other 197 (25.6) Cause of failure Pre-renal 386 (40.1) Renal 304 (39.5) Post-renal 87 (11.3) Type of failure Acute 640 (83.1) Acute on top of chronic 130 (16.9) graphic data (age, sex), underlying illnesses, laboratory find- ings (urea, creatinine, blood urea nitrogen, potassium, blood gas analyses, urinalysis), ultrasonography findings, causes of failure (pre-renal, renal, post renal), type of failure (acute, acute on chronic), etiologic cause of the failure, and the fi- nal outcome of the patients (mortality, need for dialysis). Di- agnosis of AKI and its cause was made by a nephrologist in charge of the patient at the time of hospitalization and by considering the existing standard definitions. Etiologic causes that led to AKI via deficiencies in blood flow to the kid- ney (shock, vascular deficiencies, dehydration and . . . ) were classified in the pre-renal group, causes that acted via in- jury to the renal tissue (radio-contrast agents, medications, rhabdomyolysis and . . . ) were in the renal group and finally, causes that resulted in AKI via creating an obstacle to evacu- ation of urine (stone, tumor,. . . ) were placed in the post-renal group. 2.4. Statistical Analysis Samples were gathered via census sampling. All analyses were done using SPSS 21.0 statistical software. To describe data, frequency and percentage or mean ± standard devia- tion were used. For comparisons, chi square, or Fisher’s exact statistical tests as well as student t-test were used. For mul- tivariate analysis, logistic regression analysis was applied. In all comparisons, p less than 0.05 was considered as level of significance. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2018; 6 (1): e30 Figure 1: Frequency of acute kidney injury etiology based on pre-renal, renal, and post-renal causes. BPH: benign prostatic hyperplasia. 3. Results 3.1. Baseline characteristics 770 AKI patients with the mean age of 62.72 ± 19.79 (1 – 99) years were studied (59.1% male). Table 1 depicts the base- line characteristics of the studied patients. 477 (61.9%) pa- tients were in the age group of ≥60 years and hypertension was their most common underlying disease (45.7%). Consid- ering the presentation of about 2,444,000 individuals to the This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com S. Safari et al. 4 emergency departments of the studied hospitals during the mentioned period, prevalence of AKI was estimated as 315 in 1000000 population. 3.2. Laboratory data Mean blood urea nitrogen and creatinine of the patients were 81.57 ± 57.75 (20 – 590) mg/dl and 3.50 ± 2.20 (1.5 – 20.1) mg/dl, respectively. Hyperkalemia was reported in 106 (13.8%) and metabolic acidosis in 233 (30.3%) patients. The results of urinalysis was available for 520 patients, which in- dicated 14 (1.8%) cases of > 50 red blood cells, 40 (5.2%) blood positive cases, 29 (3.8%) cases of high white blood cells, 59 (7.7%) protein positive cases, 27 (3.5%) cast positive cases, 40 (5.2%) ketone positive cases, and 23 (3.0%) bacteria positive cases. 3.3. Ultrasonography findings Kidney ultrasonography findings were available for 664 of the studied patients. Regarding the size of the kidney, 472 (70.9%) cases were normal, 110 (16.5%) were atrophic, and 84 (12.6%) cases of hydronephrosis were reported. Other ul- trasonography findings consisted of 60 (9.0%) cases of simple cysts, 41 (6.2%) cases of stone, and 28 (4.2%) calcification. 3.4. Etiologic causes 690 (89.61%) cases of AKI were pre-renal or renal (table 1). Figure 1 shows the frequency of etiologic causes of AKI based on types of pre-renal, renal, and post-renal. Among the pre- renal causes, 74 (73.3%) cases were due to different types of shock (p < 0.001). the most common etiologic causes of AKI in pre-renal group were hypotension (57.3%) and fail- ure of renal vessels (31.6%). In addition, regarding the re- nal types, rhabdomyolysis (35.0%), medication (17.5%) and chemotherapy (15.3%) and in post-renal types, kidney stone (34.5%) were the most common etiologic causes. 3.5. Patient outcome In the end, 327 (42.5%) patients needed dialysis 167 (51.2%) of which underwent dialysis once, 79 (24.2%) twice, 44 (13.5%) 3 times, and 36 (11.1%) underwent dialysis 4 times or more. 169 (21.9%) patients died, in 69 (8.9%) cases the cause of death was diagnosed due to AKI. In other words, by prevent- ing AKI, 8.9% of mortalities were preventable. 3.6. Factors related to mortality Table 2 has evaluated the correlation of various factors with mortality. The rate of mortality in patients significantly corre- lated with sex (p = 0.001), age over 60 years (p = 0.027), hyper- kalemia (p < 0.001), metabolic acidosis (p < 0.001), the cause of failure (p < 0.001), need for dialysis (p = 0.031), and type of failure (p = 0.014). Dead patients had significantly higher serum creatinine levels (4.14 ± 2.60 vs. 3.32 ± 2.03 mg/dl; p<0.001) and blood urea nitrogen (99.56 ± 74.30 vs. 76.51 ±51.11 mg/dl; p<0.001). The results of multivariate analysis was indicative of the sig- nificant and independent correlation of sex (p = 0.001), age over 60 years (p = 0.001), blood urea nitrogen level (p < 0.001), hyperkalemia (p < 0.001), metabolic acidosis (p < 0.001), cause of failure (p = 0.001), and finally, type of failure (p = 0.009) with mortality. 4. Discussion Based on the findings of the present study, the total preva- lence of AKI in patients presenting to the emergency depart- ments of the evaluated hospitals was 315 for each 1000000 population and preventable mortality rate due to AKI was es- timated to be 28.2 cases in each 1000000 population. The most important preventable AKI cases in the pre-renal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. Hoste et al. in a study in 2006 emphasized that even lit- tle changes in renal functionality of the hospitalized patients can have adverse effects on their final outcome (13). The re- sults of studies show that patients with AKI who need dialysis are in higher risk for chronic kidney failure and permanent need for dialysis (14, 15). The prevalence of AKI is widely different among various stud- ies and from 1811 to 3000 individuals in 1 million has been reported among hospitalized patients (2, 16). Of course, this rate has been reported much higher in critically ill patients. The results of the study by Hoste et al. are indicative of 67.2% prevalence of AKI in critically ill patients hospitalized in ICU (17). Additionally, Ralib et al. in addition to confirming the findings of the mentioned study showed that 60% of AKI cases in critically ill patients happen in the initial 48 hours of their hospitalization in ICU (18). The results of a study in Iran was indicative of the exceptionally high prevalence of 49.1% of AKI and 2.7% mortality due to it following open heart surgery (19). The reason for the low prevalence found in this study might be the research environment. Because emergency depart- ment patients can be considered as a sample of community acquired AKI cases and not imposed by hospitalization and etc. Therefore, considering this point, the low prevalence ob- tained can be explained. Based on the results of the present study, more than 80% of AKI cases had happened in individ- uals over 50 years of age, which is in line with the findings of previous studies in this regard (2, 3). In the present study, hypertension and diabetes were the most common comor- bidities of AKI (62.1%). In addition, pre-renal types with 40.1% prevalence were the This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 5 Emergency. 2018; 6 (1): e30 Table 2: Correlation of different factors with mortality Variable Dead Alive P value Sex Male 119 (26.2) 336 (73.8) <0.001 Female 50 (15.8) 265 (84.2) Age < 60 52 (17.7) 241 (82.3) 0.027 ≤ 60 117 (24.5) 360 (75.5) Ultrasonographic size of kidney Normal 98 (20.8) 374 (79.2) Atrophic 23 (20.9) 87 (79.1) 0.051 hypertrophic 8 (9.5) 76 (90.5) Hyperkalemia Yes 43 (40.6) 63 (59.4) < 0.001 No 126 (19.0) 538 (81.0) Metabolic acidosis Yes 82 (35.2) 151 (64.8) < 0.001 No 87 (16.2) 450 (83.8) Cause of failure Pre-renal 99 (26.1) 280 (73.9) Renal 68 (22.4) 236 (77.6) < 0.001 Post-renal 2 (2.3) 85 (97.7) Type of failure Acute 151 (23.6) 489 (76.4) 0.014 Acute on top of chronic 18 (13.8) 112 (86.2) Need for dialysis Yes 84 (25.7) 243 (74.3) 0.031 No 85 (19.2) 387 (80.8) Number of dialysis sessions < 3 times 62 (25.2) 184 (74.8) 0.852 ≥ 3 times 21 (26.2) 59 (73.8) most frequent and the most common cause of them was re- ported as various types of shock. Chertow et al. epidemiolog- ically evaluated patients with AKI and introduced decreased blood flow to the kidney, major surgeries, and injection of radio-contrast as important factors related to different types of pre-renal failures (20). Although many studies have been done on the epidemiology of AKI in different places all over the world, due to the dif- ferences present in the definitions of AKI as well as different environments we have seen dissimilar reports regarding the prevalence and outcome of these patients. Additionally, the etiologic causes of AKI vary in different countries. For these reasons, it seems that different countries should do their own studies on the burden of this disease in their country to be able to act towards preventing the disease by identifying the causes. Based on the results of this study and as might have been predicted before, the pre-renal and renal causes were at the top of the causes of failure. Modification of lifestyle and reducing the burden of non-communicable chronic diseases such as hypertension, diabetes, dyslipidemia and . . . can re- sult in reduction in the prevalence of a major part of pre-renal cases by decreasing the prevalence of vascular diseases. In addition, with aging of the population and increase in preva- lence of diseases such as sepsis in these ages, more attention should be paid regarding dehydration and prevention of sep- tic shock occurrence in these patients. More care should be taken regarding the use of nephrotoxic agents such as radio- contrasts as well as traumatic rhabdomyolysis, which is very important due to Iran being affected with many natural dis- asters and traffic accidents (21-25). It seems that by performing a multi-center study around Iran and identifying preventable causes of AKI and increas- ing public awareness in this regard, we can take a big step towards improving public health and decreasing the burden of AKI. 5. Limitation Missing data in some profiles and not being able to contact patients for follow-up of treatment process as well as limited sample size are among the limitations of this study. Defini- tion of AKI and its causes were recorded based on the opin- ion of the nephrologist in charge of the patient and therefore, this can impair the results to some extent. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com S. Safari et al. 6 6. Conclusion Based on the findings of the present study, the total preva- lence of AKI in patients presenting to the emergency depart- ments of the evaluated hospitals was 315 for each 1000000 population and preventable mortality rate due to AKI was es- timated to be 28.2 cases in each 1000000 population. In ad- dition, the most important preventable AKI cases in the pre- renal group included shock, sepsis, and dehydration; in the renal group they included rhabdomyolysis and intoxication; and stones in the post-renal group. 7. Appendix 7.1. Acknowledgements The present article is derived from Dr. Meysam Heydar- iâĂŹs thesis for receiving his specialist degree in emergency medicine, performed under supervision of Dr. Saeed Safari. 7.2. Author contribution All the authors met the 4 criteria recommended by the inter- national committee of medical journal editors for gaining au- thorship. 7.3. Funding/Support None. 7.4. Conflict of interest None. References 1. Webb S, Dobb G. ARF, ATN or AKI? It’s now acute kidney injury. Anaesthesia and intensive care. 2007;35(6):843-4. 2. Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. Journal of the American Society of Nephrology. 2007;18(4):1292-8. 3. Ali T, Roderick P. Epidemiology of Acute Kidney Injury. In: JÃűrres A, Ronco C, Kellum JA, editors. Management of Acute Kidney Problems. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. p. 63-73. 4. Bagshaw SM, George C, Bellomo R. Changes in the in- cidence and outcome for early acute kidney injury in a cohort of Australian intensive care units. Critical Care. 2007;11(3):R68. 5. Lameire N, Van Biesen W, Vanholder R. The changing epi- demiology of acute renal failure. Nature Clinical Practice Nephrology. 2006;2:364. 6. Metcalfe W, on behalf of the Scottish Renal R, Simp- son M, on behalf of the Scottish Renal R, Khan IH, on behalf of the Scottish Renal R, et al. Acute renal fail- ure requiring renal replacement therapy: incidence and outcome. QJM: An International Journal of Medicine. 2002;95(9):579-83. 7. Hoste EA, Schurgers M. Epidemiology of acute kidney in- jury: how big is the problem? Critical care medicine. 2008;36(4):S146-S51. 8. Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqah- tani F, Koulouridis I, et al. World incidence of AKI: a meta-analysis. Clinical Journal of the American Society of Nephrology. 2013;8(9):1482-93. 9. Xu X, Nie S, Liu Z, Chen C, Xu G, Zha Y, et al. Epidemi- ology and clinical correlates of AKI in Chinese hospital- ized adults. Clinical Journal of the American Society of Nephrology. 2015:CJN. 02140215. 10. 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. 2017:sfw134-sfw. 11. Batoul K, Anoshirvan K, Marjan M, Seyed Moham- madreza H, Mehdi Kazempoor D. Acute kidney injury risk factors for icu patients following cardiac surgery: The application of joint modeling. Trauma Monthly. 2016;21(4). 12. Batoul K, Anoshirvan K, Marjan M, Mehdi Kazempoor D, Seyed Mohammadreza H. Acute kidney injury in ICU patients following non-cardiac surgery at Masih Daneshvari Hospital: Joint modeling application. Tanaf- fos. 2015;14(1):49-54. 13. Hoste EA, Kellum JA. Acute kidney injury: epidemiology and diagnostic criteria. Current opinion in critical care. 2006;12(6):531-7. 14. Wald R, Quinn RR, Luo J, et al. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA. 2009;302(11):1179-85. 15. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. The Lancet. 2012;380(9843):756-66. 16. Hoste EAJ, Schurgers M. Epidemiology of acute kidney injury: How big is the problem? Critical Care Medicine. 2008;36(4):S146-S51. 17. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. In- tensive care medicine. 2015;41(8):1411-23. 18. Ralib AM, Nor MBM. Acute kidney injury in a Malaysian intensive care unit: Assessment of incidence, risk factors, and outcome. Journal of critical care. 2015;30(3):636-42. 19. MirMohammad-Sadeghi M, Fotouhi E, Beigi-Habibabadi H, Mortazavi M, Hosseini S-M, Nematbakhsh M. The Prevalence of Acute Kidney Injury in Patients Undergo- ing Coronary Artery Bypass Graft Surgery. Journal of Isfa- han Medical School. 2013;31(251). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 7 Emergency. 2018; 6 (1): e30 20. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. Journal of the American Society of Nephrology. 2005;16(11):3365-70. 21. Iraj N, Saeed S, Mostafa H, Houshang S, Ali S, Farin RF, et al. Prophylactic fluid therapy in crushed victims of Bam earthquake. The American journal of emergency medicine. 2011;29(7):738-42. 22. Safari S, Najafi I, Hosseini M. Outcomes of fasciotomy in patients with crush-induced acute kidney injury af- ter Bam earthquake. Iranian journal of kidney diseases. 2011;5(1):25. 23. Hosseini M, Safari S, Sharifi A, Amini M, Farokhi FR, Sanadgol H, et al. Wide spectrum of traumatic rhab- domyolysis in earthquake victims. Acta Medica Iranica. 2009;47(6):459-64. 24. Hashemi B, Safari S, Hosseini M, Yousefifard M, Erfani E, Baratloo A, et al. A systematic review of Iranian ex- periences in seismo-nephrology. Archives of trauma re- search. 2016;5(2):e28796. 25. Safari S, Yousefifard M, Hashemi B, Baratloo A, Forouzan- far MM, Rahmati F, et al. The Role of Scoring Systems and Urine Dipstick in Prediction of Rhabdomyolysis-induced Acute Kidney Injury A Systematic Review. 2016;10(3):101. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Introduction Methods Results Discussion Limitation Conclusion Appendix References