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Acute kidney injury after hip fracture surgery among aging population: Evaluation of incidence and covariates
European Geriatric Medicine 3 (2012) 345–348
Available online at
www.sciencedirect.com
Research paper
Acute kidney injury after hip fracture surgery among aging population: Evaluation of incidence and covariates Z. Eren a,*, C¸. Uluc¸ay b, E. C¸ig˘dem Kaspar c, F. Altıntas¸ b, G. Kantarcı a a
Department of Nephrology, Yeditepe University Hospital, Istanbul, Turkey Department of Orthopedics and Traumatology, Yeditepe University Hospital, Istanbul, Turkey c Department of Biostatistics, Yeditepe University Medical School, Istanbul, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 10 May 2012 Accepted 12 July 2012 Available online 14 August 2012
Purpose: Acute kidney injury (AKI) is a serious complication after hip fracture surgery in aging population. This study was conducted to determine the incidence of acute kidney injury and the associated risk factors. Methods: In a retrospective cohort of 214 patients hospitalized for hip fracture having undergone surgery, we examined the incidence of acute kidney injury defined according to the RIFLE (risk, injury, failure, loss, end stage kidney disease) Criteria and factors contributing to AKI. Results: Among the included 214 patients, AKI occurred in 36 cases (16.8%), at the most two days after admission, and all patients recovered to their baseline serum creatinine levels within 8 days. The number of patients undergoing renal replacement therapy (RRT) was three (1.40%), with no need of replacement therapy on hospital discharge. The baseline estimated glomerular filtration rate (eGFR), serum potassium levels at admission, and female sex were determined to be independent predictors of AKI development (OR = 0.959, 95% CI, 0.93–0.98; OR = 2.76, 95% CI, 1.24–6.14; and OR = 0.377, 95% CI, 0.34– 5.14, respectively). Conclusion: AKI was a frequent event after surgery for hip fracture and, although transient, was associated with longer hospitalization. Baseline renal function was an independent predictor. AKI in hip fracture patients should be managed collaboratively by orthopedists and nephrologists to increase our knowledge and improve clinical approach. ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Acute kidney injury Hip fracture Surgery Elderly patients
1. Introduction Hip fracture is a serious healthcare problem expected to increase with aging population and associated with significant morbidity and mortality [1,2]. Development of acute kidney injury (AKI) during the perioperative period is associated with prolonged hospital stay and poor outcomes [3–5]. Most studies have evaluated the development of AKI in setting of hip fractures and have used several definitions when describing changes to kidney functions. Until recently, the inherent problem was the lack of consensus on a definition of acute renal dysfunction (ARD). However, multiple definitions of AKI have made it difficult to make comparisons across studies and populations. The Acute Dialysis Quality Initiative (ADQI) working group, which consists of experts in the fields of nephrology and critical care medicine, recently established a consensus definition for AKI, * Corresponding author. Devlet Yolu Ankara Cad.N: 102-104, Kozyatag˘ı, 34752 Istanbul, Turkey. Tel.: +216 5784095 96; fax: +216 578 4959. E-mail address: [email protected] (Z. Eren).
called the RIFLE Criteria: Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage kidney. The RIFLE classification defines three categories of AKI based on severity (risk, injury, and failure) and two categories based on clinical outcome (loss and end-stage kidney disease). The RIFLE classifications were further refined by the Acute Kidney Initiative Network (AKIN) group [6]. Determining the incidence and outcomes associated with hip fracture surgery is critical to understanding the overall burden of the disease as well as its natural history, morbidity, and mortality. Incidence estimates for AKI associated with hip fracture have ranged between 16–24.44% [5,8]. This wide range may be attributable to the use of different definitions of AKI, differences in the observation periods, and/or heterogeneity of the selected populations. In addition, development of AKI in hip fracture patients has been increasingly recognized as an independent risk factor for morbidity and mortality [9,10]. We conducted this present study to determine the incidence and clinical predictors of AKI in Yeditepe University Hospital, Orthopaedics and Traumatology Clinic, Istanbul, Turkey.
1878-7649/$ – see front matter ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2012.07.456
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Z. Eren et al. / European Geriatric Medicine 3 (2012) 345–348
Table 1 Baseline characteristics of the patients with hip fracture. No AKI n = 178 (83.18%)
AKI n = 36 (16.82%)
P value
Demographic characteristics Age – yrs (mean SD) Female – sex n (%) BMI
77.12 10.36 130 (89%) 26.02 4.93
80.75 9.16 16 (11%) 25.69 3.82
0.052 0.001 0.707
Day of admission after the incident
0.42 0.79
1.06 1.17
0.003
Length of hospital stay (day)
4.31 1.22
7.44 2.67
0.000
Comorbidities n (%) Diabetes mellitus Hypertension Chronic kidney disease Previous CVA Documented coronary artery disease Previous MI Previous coronary revascularization Co-morbidities > 2
39 (78%) 129 (81.6%) 42 (61.8%) 12 (80%) 39 (78%) 13 (81.2%) 12 (85.7%) 27 (62.9%)
11 (22%) 29 (18.4%) 26 (38.2%) 3 (20%) 11 (22%) 3 (18.8%) 2 (14.3%) 16 (37.2%)
0.265 0.315 0.000 0.734 0.265 0.831 0.793 0.001
Selected medications ACEi ARB NSAID
47 (87.0%) 42 (84.0%) 69 (84.1%)
7 (13.0%) 8 (16.0%) 13 (15.9%)
0.381 0.859 0.765
Variables
CVA: cerebrovascular accident, MI: myocardial infarction, CKD: chronic kidney disease; ACEi: angiotensin converting enzyme inhibitor, ARB: angiotensin receptor blocker; NSAID: non-steroidal anti-inflammatory drugs. P < 0.05: statistically significant.
2. Patients and methods A retrospective cohort study was conducted with patients with hip fractures. The study was approved by the Clinical Research Review Board of Yeditepe University Medical School. Informed consent was waived due to the retrospective nature of the study. 2.1. Patient population All patients older than 65 years admitted with hip fractures to the Orthopaedics and Traumatology Clinic over a 3-year period (2008–2011) were included. We identified 220 consecutive patients with these diagnoses. Patients with previously diagnosed end-stage renal disease on renal replacement therapy (n = 6) were excluded. As a result, 214 patients were evaluated. 2.2. Clinical and laboratory data collection Data were obtained from the Hospital Information System (HIS) and verified with the written records of each patient. HIS is a computerised system used for daily patient documentation. Standard demographic, clinical, and physiological data were retrieved. The demographic information included age, sex, body mass index (BMI), and the length of hospital stay. The clinical data included the primary diagnosis, co-morbidities (diabetes mellitus [DM)], hypertension [HT], chronic kidney disease [CKD], history of cerebrovascular accidents [CVA], myocardial infarction [MI] or coronary revascularisation, and documented coronary artery disease), and medications (Table 1). Serum creatinine (SCr) and blood urea nitrogen (BUN) values at admission and discharge were recorded, as were their peak values. We also recorded serum sodium, potassium, haemoglobin, and white blood cell values at admission and discharge. Hemodynamic parameters (systolic and diastolic blood pressure and heart rate [HR]) were recorded (Table 2). 2.3. Identification of acute kidney injury AKI was classified according to serum creatinine levels, as proposed by the RIFLE classification (Table 3). AKI was classified into three categories based on severity (risk, injury, and failure). The
outcome RIFLE categories loss and end-stage kidney disease were not evaluated in this study. AKI-R was considered if there was an increase in SCr to more than 1.5 times baseline value or a urinary output lower than 0.5 mL/kg per hour for 6 h. AKI-I was considered if there was an increase in SCr to more than twice the baseline value or a urinary output lower than 0.5 mL/kg per hour for 12 h. AKI-F was considered if there was an increase in SCr to more than three times the baseline value or a urinary output lower than 0.3 mL/kg per hour for 24 h. Patients were assigned to RIFLE categories according to SCr only. The serum creatinine levels used in AKI classification were the peak values measured during the hospital stay. Baseline SCr was defined as the creatinine measurement at admission. For some patients, SCr at discharge was lower than SCr at admission, so this value was considered to be the basal level. Chronic kidney disease was diagnosed in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/ min/1.73 m2 for greater than 3 months, based on the guidelines of the National Kidney Foundation [17]. Baseline GFR was estimated using the four-component (age, race, sex, and serum creatinine levels) Table 2 Baseline laboratory and hemodynamic characteristics of the patients. Variables BUN (mg/dl) Creatinine (mg/dl) eGFR (ml/min/1.73m2) Sodium (mg/dl)
No AKI n = 178 (83.19%) 20.09 7.05
AKI n = 36 (16.82%)
P value
30.94 16.19
0.000
0.86 0.32
1.53 1.17
0.000
77.52 23.48
48.47 21.13
0.000
139.18 2.68
138.33 3.00
0.092
Potassium (mg/dl)
4.12 0.55
4.63 0.49
0.000
Hemoglobin (gr/dl)
11.85 1.74
11.67 1.25
0.557
White blood cells
12.25 2.75
13.48 3.62
0.022
125.42 14.45 71.83 11.28
0.932 0.779
77.58 9.31
0.067
Systemic pressure (mmHg) Systolic 125.67 16.89 Diastolic 74.25 51.39 Heart rate (bpm)
81.75 12.91
BUN: blood urea nitrogen; eGFR: estimated glomerulary filtration rate. P < 0.05: statistically significant.
Z. Eren et al. / European Geriatric Medicine 3 (2012) 345–348
347
Table 3 Classification of acute kidney injury according to RIFLE Criteria. Category
Serum creatine criteria
Urine output criteria
Risk
Increase in serum creatinine 1.5 from baseline or decrease in GFR 5%
Less than 0.5 ml/kg per hours for more than 6 hours
Injury
Increase in serum creatinine 2.0 from baseline or decrease in GFR 50%
Less than 0.5 ml/kg per hours for more than 12 hours
Failure
Increase in serum creatinine 3.0 from baseline or decrease in GFR 75%
Less than 0.3 ml/kg per hours for 24 hours or anuria for 12 hours
Loss
Complete loss of renal functions for > 4 weeks
ESKD
Need for RRT for > 3 months
modification of the diet in the renal disease equation: estimated GFR = 186 (serum creatinine level in mg/dl) 1.154 (age in years) 0.203. The product of this formula is multiplied by a correction factor of 0.742 for women and 1.21 for African Americans [6–8]. We assessed the incidence and the risk factors of AKI after hip fracture surgery. In-hospital mortality was considered to be an outcome. 2.4. Statistical analyses Continuous variables are presented as mean SD, and discrete variables are presented as frequencies and percentages. Two independent sample t tests were applied to evaluate the differences in means between two groups. A Chi-square test was used to compare the frequencies of the groups. Multiple logistic regression analysis was used to evaluate the independent correlates of AKI. Parameters with a P value < 0.05 in a univariate analysis were included in the model. The model fit was evaluated by the Hosmer-Lemoshow goodness-of-fit test. Two-tailed P values < 0.05 were considered statistically significant. Statistical analyses were performed using SPSS version 19.0 (SPSS Inc., Chicago, IL, USA). 3. Results 3.1. Baseline characteristics The demographic, clinical and laboratory characteristics of the patients with and without AKI are presented in Tables 1 and 2. The BUN, potassium levels and white blood cell counts were significantly higher in patients who later developed AKI and eGFR was significantly lower than those who did not. Patients with AKI were more elderly, had a higher incidence of chronic kidney disease, more than two co-morbidities and seemed to have applied to the hospital later when compared with no AKI patients. The length of hospital stay was significantly longer in patients with AKI than no AKI patients (P < 0.00). 3.2. Incidence of acute kidney injury AKI developed in 36 patients (16.8%). The mean time from admission to the development of AKI was 1.20 0.66 (min 0, max two days). All patients with AKI recovered to baseline SCr levels within mean 4.84 1.34 days (min three, max eight days). According to RIFLE classification 28 patient (13.1%) developed risk for renal dysfunction, one patient (0.5%) injury to the kidney and six patients (2.8%) failure of kidney function. The number of patients undergoing renal replacement therapy (RRT) was three (1.4%), without any need of replacement therapy on hospital discharge. 3.3. Predictors of acute kidney injury Logistic regression analyses were used to identify predictors of AKI in hip fracture patients that underwent surgery. In univariate
analysis female gender (OR = 0.295, 95%CI, 0.141–0.617), a history of chronic kidney disease (OR = 8.419, 95% CI, 3.756–18.873), more than two co-morbidities (OR = 1.909, 95% CI, 1.328–2.745), higher potassium levels at admission (OR = 5.814, 95% CI, 2.712–12.466) and lower eGFR levels (OR = 0.944, 95% CI, 0.924–0.963) were significantly associated with AKI whereas after multivariable adjustment, only female gender, serum potassium levels at admission and lower eGFR levels (OR = 0.377, 95% CI, 0.156– 0.909; OR = 2.765, 95% CI, 1.245–6.142 and OR = 0.97, 95% CI, 0.93– 1.007 respectively) turned out to be the independent predictors of AKI. 3.4. Association between acute kidney injury and outcomes A total of three (1.40%) inhospital deaths occurred in early postoperative period and the small number of patients did not allow assessing statistically association with AKI. 4. Discussion This study indicated the incidence of acute kidney injury among patients with hip fractures having undergone surgery was 16.8%. The incidence of AKI ranged from 16% to 24.44% in two recent studies [5,9], and our result is consistent with those studies. The wide ranges of reported incidence may be attributable to differences in the selected populations with respect to ethnicity or geography. Moreover, postoperative AKI is associated with prolonged hospital stay as demonstrated in our study [5]. Many studies have evaluated the association of various predictors with the occurrence of AKI in noncardiac and cardiac surgery patients [11–13]. In addition to describing the incidence of AKI in our study, we evaluated many patient characteristics to determine the independent risk factors for AKI in patients with hip fracture. Age, diabetes, hypertension, emergency surgery, congestive heart disease, and chronic kidney disease have emerged as independent predictors of AKI in different studies conducted among various surgical patients [14–16]. Although age; being female; and having a history of chronic kidney disease, more than two co-morbidities, high serum potassium levels, and lower eGFR levels were significantly associated with AKI in our study, only being female, having high serum potassium levels, and having lower eGFR levels turned out to be the independent predictors of AKI. The most important risk factor for developing AKI is the presence of comorbidities. In particular, the presence of chronic kidney disease dramatically increases the risk of developing renal injury after an acute insult [17–19]. Our relatively small data set is consistent with these previous studies in demonstrating the importance of chronic kidney disease as a predictor of AKI in patients with hip fracture who undergo surgery. Unfortunately, postoperative AKI is often multifactorial. Some risk factors are associated with the preoperative clinical status [10] while others are related to the surgical procedure and its complications. Moreover, the experience of the anesthesiological team, as well as the types of medications and procedures used at an
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institution during the perioperative period, plays a significant role [9,20,21]. Several studies have shown that AKI development is associated with an increased mortality in this patient population [22,23]. In this study, we were unable to determine any association with AKI for a small number of in-hospital deaths. Our study had several limitations. The first limitation is that it was a retrospective and a single-centre study with limited sample size. Therefore, the findings may lead to misinterpretations. It would be informative to assess similar data among several institutions encompassing a large population. A second limitation is the lack of review of the contribution of nephrotoxic drugs to the development of AKI. Pharmacological treatment was modified according to clinical status and considering renal functions of patients, but details were unknown. A third limitation is that this was purely an observational study, and the mechanisms of AKI and the most appropriate treatment options for these high-risk groups were not assessed. Additional prospective studies are warranted to establish underlying mechanisms of renal injury and to analyse whether changes in preventative action and treatment approaches would affect outcomes. In conclusion, we found that an AKI is an important and frequent event after hip fracture surgery in elderly. The baseline estimated glomerular filtration rate was found to be the most important independent predictor of AKI development in this population. Although the predominant mechanism of AKI and its negative effect on the outcome in hip fracture patients are not completely understood, the syndrome is clearly multifactorial. In addition, the presence of a pre-existing CKD may have an impact on incidence of AKI. In the future, this serious problem after hip surgery should be managed collaboratively to increase our knowledge and improve clinical approaches. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Panula J, Pihlajamaki H, Mattila VM, Jaatinen P, Vahlberg T, Aarnio P, et al. Mortality and cause of death in hip fracture patients aged 65 or older – a population-based study. BMC Musculoskelet Disord 2011;12:105 [doi:10.1186/1471-2474-12-105]. [2] Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 2009;20:1633–50.
[3] Gong Y, Zhang F, Ding F, Gu Y. Elderly patients with acute kidney injury (AKI): clinical features and risk factors for mortality. Arch Gerontol Geriatr 2012;54: e47–51. [4] Jafari SM, Huang R, Joshi A, Parvizi J, Hozack WJ. Renal impairment following total joint arthroplasty: who is at risk? J Arthroplasty 2010;25:49–53. [5] Bennet SJ, Berry OM, Goddard J, Keating JF. Acute renal dysfunction following hip fracture. Injury 2010;41:335–8. [6] Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204–12. [7] 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. [8] Levey AS, Stevens LA. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 2010;55:622–7. [9] Azevedo VL, Silveira MA, Santos JN, Braz JR, Braz LG, Mo´dolo NS. Postoperative renal function evaluation, through RIFLE criteria, of elderly patients who underwent femur fracture surgery under spinal anesthesia. Ren Fail 2008;30:485–90. [10] Aveline C, Leroux A, Vautier P, Cognet F, Le Hetet H, Bonnet F. Risk factors for renal dysfunction after total hip arthroplasty. Ann Fr Anesth Reanim 2009;28: 728–34. [11] Singh Mangat K, Mehra A, Yunas I, Nightingale P, Porter K. Is estimated perioperative glomerular filtration rate associated with post-operative mortality in fractured neck of femur patients? Injury 2008;39:1141–6. [12] Kheterpal S, Tremper KK, Englesbe MJ, O’Reilly M, Shanks AM, Fetterman DM, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology 2008;107:892–902. [13] Noyez L. Influence of the definition of acute renal failure post-cardiac surgery on incidence, patient identification, and identification of risk factors. Eur J Cardiothorac Surg 2011;39:e8–12. [14] Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Crit Care 2009;13:R79. [15] Noor S, Usmani A. Postoperative renal failure. Clin Geriatr Med 2009;24:721–9. [16] Drawz PE, Miller RT, Sehgal AR. Predicting hospital-acquired acute kidney injury – a case-controlled study. Ren Fail 2008;30:848–55. ˜ o F, Ortun ˜ o J. The elderly patient with acute renal failure. J Am [17] Pascual J, Lian Soc Nephrol 1995;6:144–53. [18] Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis 2002;39:930–6. [19] Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B, POSH Investigators. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH). Eur Heart J 2006;27:1216–22. [20] White SM, Rashid N, Chakladar A. An analysis of renal dysfunction in 1511 patients with fractured neck of femur: the implications for peri-operative analgesia. Anaesthesia 2009;64:1061–5. [21] Ricci Z, Luciano R, Favia I, Garisto C, Muraca M, Morelli S, et al. High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery. Crit Care 2011;15:R160. [22] S¸ener M, Onar V, Kazımog˘lu C, Yag˘cı S. Mortality and morbidity in elderly patients who underwent partial prosthesis replacement for proximal femoral fracture. Joint Dis Surg 2009;20:11–7. [23] Wiles MD, Moran CG, Sahota O, Moppett IK. Nottingham Hip Fracture Score as a predictor of one year mortality in patients undergoing surgical repair of fractured neck of femur. Br J Anaesth 2011;106:501–4.
Available online at
www.sciencedirect.com
Research paper
Acute kidney injury after hip fracture surgery among aging population: Evaluation of incidence and covariates Z. Eren a,*, C¸. Uluc¸ay b, E. C¸ig˘dem Kaspar c, F. Altıntas¸ b, G. Kantarcı a a
Department of Nephrology, Yeditepe University Hospital, Istanbul, Turkey Department of Orthopedics and Traumatology, Yeditepe University Hospital, Istanbul, Turkey c Department of Biostatistics, Yeditepe University Medical School, Istanbul, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 10 May 2012 Accepted 12 July 2012 Available online 14 August 2012
Purpose: Acute kidney injury (AKI) is a serious complication after hip fracture surgery in aging population. This study was conducted to determine the incidence of acute kidney injury and the associated risk factors. Methods: In a retrospective cohort of 214 patients hospitalized for hip fracture having undergone surgery, we examined the incidence of acute kidney injury defined according to the RIFLE (risk, injury, failure, loss, end stage kidney disease) Criteria and factors contributing to AKI. Results: Among the included 214 patients, AKI occurred in 36 cases (16.8%), at the most two days after admission, and all patients recovered to their baseline serum creatinine levels within 8 days. The number of patients undergoing renal replacement therapy (RRT) was three (1.40%), with no need of replacement therapy on hospital discharge. The baseline estimated glomerular filtration rate (eGFR), serum potassium levels at admission, and female sex were determined to be independent predictors of AKI development (OR = 0.959, 95% CI, 0.93–0.98; OR = 2.76, 95% CI, 1.24–6.14; and OR = 0.377, 95% CI, 0.34– 5.14, respectively). Conclusion: AKI was a frequent event after surgery for hip fracture and, although transient, was associated with longer hospitalization. Baseline renal function was an independent predictor. AKI in hip fracture patients should be managed collaboratively by orthopedists and nephrologists to increase our knowledge and improve clinical approach. ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Acute kidney injury Hip fracture Surgery Elderly patients
1. Introduction Hip fracture is a serious healthcare problem expected to increase with aging population and associated with significant morbidity and mortality [1,2]. Development of acute kidney injury (AKI) during the perioperative period is associated with prolonged hospital stay and poor outcomes [3–5]. Most studies have evaluated the development of AKI in setting of hip fractures and have used several definitions when describing changes to kidney functions. Until recently, the inherent problem was the lack of consensus on a definition of acute renal dysfunction (ARD). However, multiple definitions of AKI have made it difficult to make comparisons across studies and populations. The Acute Dialysis Quality Initiative (ADQI) working group, which consists of experts in the fields of nephrology and critical care medicine, recently established a consensus definition for AKI, * Corresponding author. Devlet Yolu Ankara Cad.N: 102-104, Kozyatag˘ı, 34752 Istanbul, Turkey. Tel.: +216 5784095 96; fax: +216 578 4959. E-mail address: [email protected] (Z. Eren).
called the RIFLE Criteria: Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage kidney. The RIFLE classification defines three categories of AKI based on severity (risk, injury, and failure) and two categories based on clinical outcome (loss and end-stage kidney disease). The RIFLE classifications were further refined by the Acute Kidney Initiative Network (AKIN) group [6]. Determining the incidence and outcomes associated with hip fracture surgery is critical to understanding the overall burden of the disease as well as its natural history, morbidity, and mortality. Incidence estimates for AKI associated with hip fracture have ranged between 16–24.44% [5,8]. This wide range may be attributable to the use of different definitions of AKI, differences in the observation periods, and/or heterogeneity of the selected populations. In addition, development of AKI in hip fracture patients has been increasingly recognized as an independent risk factor for morbidity and mortality [9,10]. We conducted this present study to determine the incidence and clinical predictors of AKI in Yeditepe University Hospital, Orthopaedics and Traumatology Clinic, Istanbul, Turkey.
1878-7649/$ – see front matter ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2012.07.456
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Z. Eren et al. / European Geriatric Medicine 3 (2012) 345–348
Table 1 Baseline characteristics of the patients with hip fracture. No AKI n = 178 (83.18%)
AKI n = 36 (16.82%)
P value
Demographic characteristics Age – yrs (mean SD) Female – sex n (%) BMI
77.12 10.36 130 (89%) 26.02 4.93
80.75 9.16 16 (11%) 25.69 3.82
0.052 0.001 0.707
Day of admission after the incident
0.42 0.79
1.06 1.17
0.003
Length of hospital stay (day)
4.31 1.22
7.44 2.67
0.000
Comorbidities n (%) Diabetes mellitus Hypertension Chronic kidney disease Previous CVA Documented coronary artery disease Previous MI Previous coronary revascularization Co-morbidities > 2
39 (78%) 129 (81.6%) 42 (61.8%) 12 (80%) 39 (78%) 13 (81.2%) 12 (85.7%) 27 (62.9%)
11 (22%) 29 (18.4%) 26 (38.2%) 3 (20%) 11 (22%) 3 (18.8%) 2 (14.3%) 16 (37.2%)
0.265 0.315 0.000 0.734 0.265 0.831 0.793 0.001
Selected medications ACEi ARB NSAID
47 (87.0%) 42 (84.0%) 69 (84.1%)
7 (13.0%) 8 (16.0%) 13 (15.9%)
0.381 0.859 0.765
Variables
CVA: cerebrovascular accident, MI: myocardial infarction, CKD: chronic kidney disease; ACEi: angiotensin converting enzyme inhibitor, ARB: angiotensin receptor blocker; NSAID: non-steroidal anti-inflammatory drugs. P < 0.05: statistically significant.
2. Patients and methods A retrospective cohort study was conducted with patients with hip fractures. The study was approved by the Clinical Research Review Board of Yeditepe University Medical School. Informed consent was waived due to the retrospective nature of the study. 2.1. Patient population All patients older than 65 years admitted with hip fractures to the Orthopaedics and Traumatology Clinic over a 3-year period (2008–2011) were included. We identified 220 consecutive patients with these diagnoses. Patients with previously diagnosed end-stage renal disease on renal replacement therapy (n = 6) were excluded. As a result, 214 patients were evaluated. 2.2. Clinical and laboratory data collection Data were obtained from the Hospital Information System (HIS) and verified with the written records of each patient. HIS is a computerised system used for daily patient documentation. Standard demographic, clinical, and physiological data were retrieved. The demographic information included age, sex, body mass index (BMI), and the length of hospital stay. The clinical data included the primary diagnosis, co-morbidities (diabetes mellitus [DM)], hypertension [HT], chronic kidney disease [CKD], history of cerebrovascular accidents [CVA], myocardial infarction [MI] or coronary revascularisation, and documented coronary artery disease), and medications (Table 1). Serum creatinine (SCr) and blood urea nitrogen (BUN) values at admission and discharge were recorded, as were their peak values. We also recorded serum sodium, potassium, haemoglobin, and white blood cell values at admission and discharge. Hemodynamic parameters (systolic and diastolic blood pressure and heart rate [HR]) were recorded (Table 2). 2.3. Identification of acute kidney injury AKI was classified according to serum creatinine levels, as proposed by the RIFLE classification (Table 3). AKI was classified into three categories based on severity (risk, injury, and failure). The
outcome RIFLE categories loss and end-stage kidney disease were not evaluated in this study. AKI-R was considered if there was an increase in SCr to more than 1.5 times baseline value or a urinary output lower than 0.5 mL/kg per hour for 6 h. AKI-I was considered if there was an increase in SCr to more than twice the baseline value or a urinary output lower than 0.5 mL/kg per hour for 12 h. AKI-F was considered if there was an increase in SCr to more than three times the baseline value or a urinary output lower than 0.3 mL/kg per hour for 24 h. Patients were assigned to RIFLE categories according to SCr only. The serum creatinine levels used in AKI classification were the peak values measured during the hospital stay. Baseline SCr was defined as the creatinine measurement at admission. For some patients, SCr at discharge was lower than SCr at admission, so this value was considered to be the basal level. Chronic kidney disease was diagnosed in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/ min/1.73 m2 for greater than 3 months, based on the guidelines of the National Kidney Foundation [17]. Baseline GFR was estimated using the four-component (age, race, sex, and serum creatinine levels) Table 2 Baseline laboratory and hemodynamic characteristics of the patients. Variables BUN (mg/dl) Creatinine (mg/dl) eGFR (ml/min/1.73m2) Sodium (mg/dl)
No AKI n = 178 (83.19%) 20.09 7.05
AKI n = 36 (16.82%)
P value
30.94 16.19
0.000
0.86 0.32
1.53 1.17
0.000
77.52 23.48
48.47 21.13
0.000
139.18 2.68
138.33 3.00
0.092
Potassium (mg/dl)
4.12 0.55
4.63 0.49
0.000
Hemoglobin (gr/dl)
11.85 1.74
11.67 1.25
0.557
White blood cells
12.25 2.75
13.48 3.62
0.022
125.42 14.45 71.83 11.28
0.932 0.779
77.58 9.31
0.067
Systemic pressure (mmHg) Systolic 125.67 16.89 Diastolic 74.25 51.39 Heart rate (bpm)
81.75 12.91
BUN: blood urea nitrogen; eGFR: estimated glomerulary filtration rate. P < 0.05: statistically significant.
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Table 3 Classification of acute kidney injury according to RIFLE Criteria. Category
Serum creatine criteria
Urine output criteria
Risk
Increase in serum creatinine 1.5 from baseline or decrease in GFR 5%
Less than 0.5 ml/kg per hours for more than 6 hours
Injury
Increase in serum creatinine 2.0 from baseline or decrease in GFR 50%
Less than 0.5 ml/kg per hours for more than 12 hours
Failure
Increase in serum creatinine 3.0 from baseline or decrease in GFR 75%
Less than 0.3 ml/kg per hours for 24 hours or anuria for 12 hours
Loss
Complete loss of renal functions for > 4 weeks
ESKD
Need for RRT for > 3 months
modification of the diet in the renal disease equation: estimated GFR = 186 (serum creatinine level in mg/dl) 1.154 (age in years) 0.203. The product of this formula is multiplied by a correction factor of 0.742 for women and 1.21 for African Americans [6–8]. We assessed the incidence and the risk factors of AKI after hip fracture surgery. In-hospital mortality was considered to be an outcome. 2.4. Statistical analyses Continuous variables are presented as mean SD, and discrete variables are presented as frequencies and percentages. Two independent sample t tests were applied to evaluate the differences in means between two groups. A Chi-square test was used to compare the frequencies of the groups. Multiple logistic regression analysis was used to evaluate the independent correlates of AKI. Parameters with a P value < 0.05 in a univariate analysis were included in the model. The model fit was evaluated by the Hosmer-Lemoshow goodness-of-fit test. Two-tailed P values < 0.05 were considered statistically significant. Statistical analyses were performed using SPSS version 19.0 (SPSS Inc., Chicago, IL, USA). 3. Results 3.1. Baseline characteristics The demographic, clinical and laboratory characteristics of the patients with and without AKI are presented in Tables 1 and 2. The BUN, potassium levels and white blood cell counts were significantly higher in patients who later developed AKI and eGFR was significantly lower than those who did not. Patients with AKI were more elderly, had a higher incidence of chronic kidney disease, more than two co-morbidities and seemed to have applied to the hospital later when compared with no AKI patients. The length of hospital stay was significantly longer in patients with AKI than no AKI patients (P < 0.00). 3.2. Incidence of acute kidney injury AKI developed in 36 patients (16.8%). The mean time from admission to the development of AKI was 1.20 0.66 (min 0, max two days). All patients with AKI recovered to baseline SCr levels within mean 4.84 1.34 days (min three, max eight days). According to RIFLE classification 28 patient (13.1%) developed risk for renal dysfunction, one patient (0.5%) injury to the kidney and six patients (2.8%) failure of kidney function. The number of patients undergoing renal replacement therapy (RRT) was three (1.4%), without any need of replacement therapy on hospital discharge. 3.3. Predictors of acute kidney injury Logistic regression analyses were used to identify predictors of AKI in hip fracture patients that underwent surgery. In univariate
analysis female gender (OR = 0.295, 95%CI, 0.141–0.617), a history of chronic kidney disease (OR = 8.419, 95% CI, 3.756–18.873), more than two co-morbidities (OR = 1.909, 95% CI, 1.328–2.745), higher potassium levels at admission (OR = 5.814, 95% CI, 2.712–12.466) and lower eGFR levels (OR = 0.944, 95% CI, 0.924–0.963) were significantly associated with AKI whereas after multivariable adjustment, only female gender, serum potassium levels at admission and lower eGFR levels (OR = 0.377, 95% CI, 0.156– 0.909; OR = 2.765, 95% CI, 1.245–6.142 and OR = 0.97, 95% CI, 0.93– 1.007 respectively) turned out to be the independent predictors of AKI. 3.4. Association between acute kidney injury and outcomes A total of three (1.40%) inhospital deaths occurred in early postoperative period and the small number of patients did not allow assessing statistically association with AKI. 4. Discussion This study indicated the incidence of acute kidney injury among patients with hip fractures having undergone surgery was 16.8%. The incidence of AKI ranged from 16% to 24.44% in two recent studies [5,9], and our result is consistent with those studies. The wide ranges of reported incidence may be attributable to differences in the selected populations with respect to ethnicity or geography. Moreover, postoperative AKI is associated with prolonged hospital stay as demonstrated in our study [5]. Many studies have evaluated the association of various predictors with the occurrence of AKI in noncardiac and cardiac surgery patients [11–13]. In addition to describing the incidence of AKI in our study, we evaluated many patient characteristics to determine the independent risk factors for AKI in patients with hip fracture. Age, diabetes, hypertension, emergency surgery, congestive heart disease, and chronic kidney disease have emerged as independent predictors of AKI in different studies conducted among various surgical patients [14–16]. Although age; being female; and having a history of chronic kidney disease, more than two co-morbidities, high serum potassium levels, and lower eGFR levels were significantly associated with AKI in our study, only being female, having high serum potassium levels, and having lower eGFR levels turned out to be the independent predictors of AKI. The most important risk factor for developing AKI is the presence of comorbidities. In particular, the presence of chronic kidney disease dramatically increases the risk of developing renal injury after an acute insult [17–19]. Our relatively small data set is consistent with these previous studies in demonstrating the importance of chronic kidney disease as a predictor of AKI in patients with hip fracture who undergo surgery. Unfortunately, postoperative AKI is often multifactorial. Some risk factors are associated with the preoperative clinical status [10] while others are related to the surgical procedure and its complications. Moreover, the experience of the anesthesiological team, as well as the types of medications and procedures used at an
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institution during the perioperative period, plays a significant role [9,20,21]. Several studies have shown that AKI development is associated with an increased mortality in this patient population [22,23]. In this study, we were unable to determine any association with AKI for a small number of in-hospital deaths. Our study had several limitations. The first limitation is that it was a retrospective and a single-centre study with limited sample size. Therefore, the findings may lead to misinterpretations. It would be informative to assess similar data among several institutions encompassing a large population. A second limitation is the lack of review of the contribution of nephrotoxic drugs to the development of AKI. Pharmacological treatment was modified according to clinical status and considering renal functions of patients, but details were unknown. A third limitation is that this was purely an observational study, and the mechanisms of AKI and the most appropriate treatment options for these high-risk groups were not assessed. Additional prospective studies are warranted to establish underlying mechanisms of renal injury and to analyse whether changes in preventative action and treatment approaches would affect outcomes. In conclusion, we found that an AKI is an important and frequent event after hip fracture surgery in elderly. The baseline estimated glomerular filtration rate was found to be the most important independent predictor of AKI development in this population. Although the predominant mechanism of AKI and its negative effect on the outcome in hip fracture patients are not completely understood, the syndrome is clearly multifactorial. In addition, the presence of a pre-existing CKD may have an impact on incidence of AKI. In the future, this serious problem after hip surgery should be managed collaboratively to increase our knowledge and improve clinical approaches. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Panula J, Pihlajamaki H, Mattila VM, Jaatinen P, Vahlberg T, Aarnio P, et al. Mortality and cause of death in hip fracture patients aged 65 or older – a population-based study. BMC Musculoskelet Disord 2011;12:105 [doi:10.1186/1471-2474-12-105]. [2] Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 2009;20:1633–50.
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