|Year : 2014 | Volume
| Issue : 7 | Page : 321-327
Chronic kidney disease predicts long-term mortality after major lower extremity amputation
Roland Assi1, Yorg Al Azzi2, Clinton D Protack1, Willis T Williams1, Michael R Hall1, Daniel J Wong3, Daniel Y Lu3, Penny Vasilas4, Alan Dardik1
1 Department of Surgery, Department of Veterans Affairs Connecticut Healthcare System, West Haven; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
2 Department of Medicine, Mount Sinai Hospital, Icahn School of Medicine, New York, USA
3 Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
4 Department of Surgery, Department of Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
|Date of Web Publication||18-Jul-2014|
VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, Connecticut - 06516
Source of Support: This work was supported by the resources and the use
of facilities at the VA Connecticut Healthcare System, West Haven, CT; the
contents do not represent the views of the Department of Veterans Affairs
or the United States Government,, Conflict of Interest: None
Background: Despite low peri-operative mortality after major lower extremity amputation, long-term mortality remains substantial. Metabolic syndrome is increasing in incidence and prevalence at an alarming rate in the USA. Aim: This study was to determine whether metabolic syndrome predicts outcome after major lower extremity amputation. Patients and Methods: A retrospective review of charts between July 2005 and June 2010. Results: Fifty-four patients underwent a total of 60 major lower extremity amputations. Sixty percent underwent below-knee amputation and 40% underwent above-knee amputation. The 30-day mortality was 7% with no difference in level (below-knee amputation, 8%; above-knee amputation, 4%; P = 0.53). The mean follow-up time was 39.7 months. The 5-year survival was 54% in the whole group, and was independent of level of amputation (P = 0.24) or urgency of the procedure (P = 0.51). Survival was significantly decreased by the presence of underlying chronic kidney disease (P = 0.04) but not by other comorbidities (history of myocardial infarction, P = 0.79; metabolic syndrome, P = 0.64; diabetes mellitus, P = 0.56). Conclusion: Metabolic syndrome is not associated with increased risk of adverse outcomes after lower extremity amputation. However, patients with chronic kidney disease constitute a sub-group of patients at higher risk of postoperative long-term mortality and may be a group to target for intervention.
Keywords: Chronic kidney disease, Lower extremity amputation, Metabolic syndrome, Mortality, Peripheral artery disease
|How to cite this article:|
Assi R, Al Azzi Y, Protack CD, Williams WT, Hall MR, Wong DJ, Lu DY, Vasilas P, Dardik A. Chronic kidney disease predicts long-term mortality after major lower extremity amputation. North Am J Med Sci 2014;6:321-7
|How to cite this URL:|
Assi R, Al Azzi Y, Protack CD, Williams WT, Hall MR, Wong DJ, Lu DY, Vasilas P, Dardik A. Chronic kidney disease predicts long-term mortality after major lower extremity amputation. North Am J Med Sci [serial online] 2014 [cited 2020 Sep 20];6:321-7. Available from: http://www.najms.org/text.asp?2014/6/7/321/136910
| Introduction|| |
Lower extremity amputation remains a definitive therapy for the management of ischemic disease that fails revascularization. Despite recent advances in revascularization techniques and broadening of indications, each year 55,000 to 65,000 major lower extremity amputations are performed in the USA, , making lower extremity amputation one of the most common vascular surgery procedures.
Major lower extremity amputation, either below- or above-knee amputation, is associated with significant morbidity and mortality. Multiple predictors of poor outcome after major lower extremity amputation have been reported. Patients with advanced age or coronary artery disease have poor outcomes.  In the Framingham Heart Study, the prevalence of metabolic syndrome doubled during a 10-year period and was associated with a three-fold increased risk in death.  Patients with metabolic syndrome undergoing peripheral vascular interventions have been shown to have unfavorable perioperative outcomes. , Patients who undergo above-knee amputation (AKA) have worse functional and survival outcomes compared to patients who undergo below-knee amputation (BKA). ,
The aim of our study is to identify whether comorbid diseases such as metabolic syndrome are associated with either peri-operative or long-term adverse events in patients undergoing major lower extremity amputation for ischemic disease. We have previously shown that veterans with vascular disease have more comorbid disease than non-veterans with similar diagnoses, and that these veterans form a high-risk population. , We hypothesized that these high-risk patients would have extensive comorbid diseases such as metabolic syndrome, and that peri-operative and long-term survival would be related to the presence of these risk factors. Therefore, we examined the peri-operative and long-term outcomes of veterans undergoing major lower extremity amputation.
| Patients and Methods|| |
The electronic records of all patients who underwent a major lower extremity amputation for ischemic disease at our institution between July 2005 and June 2010 were reviewed. Major lower extremity amputation was defined as amputation below the hip and above the ankle and further categorized as AKA or BKA. Amputations limited to or below the ankle or amputations for traumatic injuries were excluded.
Pre-operative, intra-operative, and post-operative data were collected. Criteria for diagnosis of metabolic syndrome were met when three or more of the following criteria were met: fasting blood glucose >110 mg/dL or previously diagnosed diabetes mellitus, BMI >30 kg/m 2 , SBP/DBP >140/90 mmHg or treatment of previously diagnosed hypertension, HDL <40 mg/dL in males or <50 mg/dL in females or specific treatment for this lipid abnormality, and fasting triglycerides >150 mg/dL or specific treatment for this lipid abnormality.  Chronic kidney disease (CKD) was defined as stage 3 or worse, corresponding to an estimated glomerular filtration rate of less than 60 mL/min/1.73 m 2 using the Modification of Diet in Renal Disease (MDRD) study equation and includes patients with End-Stage Renal Disease (ESRD) on dialysis.
Patients were followed until September 2013. Early postoperative outcomes include morbidity and mortality within 30 days of surgery or the duration of the post-operative hospitalization if the patient remained in the hospital longer than 30 days. These outcomes included 30-day mortality, revision for wound failure, conversion from BKA to AKA, myocardial infarction and stroke. Late postoperative outcomes were recorded through the end of the study period and consisted of death, development of congestive heart failure, fatal, and non-fatal myocardial infarction, stroke, and progression to ESRD.
JMP ® 9.0.0 software (SAS Institute, Cary, NC) was used for data analysis. Variables were represented as mean ± standard deviation. Categorical variables were compared with Chi-square analysis and continuous variables were compared with the t-test. Kaplan-Meier analysis was used for survival analysis, with comparison of groups using the log rank test. Demographic variables that predicted mortality were examined using the Cox proportional hazards model. All tests were double tailed with a type I error risk (alpha) equal to 5%.
| Results|| |
Fifty-four patients underwent a total of 60 major lower extremity amputations. All patients were male; the mean age was 65.9 years. Sixty percent (n = 36) underwent BKA and 40% (n = 24) underwent AKA. Seventy-eight percent of patients were Caucasian, 22% were African American. Eighteen percent had a prior contralateral amputation and 65% had a previous vascular intervention (endovascular, open or both). All the above-mentioned characteristics were not statistically different when compared between the BKA and AKA groups [Table 1].
The prevalence of comorbid conditions was extremely high in this population and is shown in [Table 1]. The most prevalent conditions were arterial hypertension (90%), diabetes mellitus (78%), metabolic syndrome (68%), history of myocardial infarction (MI, 63%), dyslipidemia (62%), chronic kidney disease (CKD, 40%), and congestive heart failure (CHF, 30%). Thirty-eight percent were dependent in their performance of activities of daily life prior to surgery. However, the prevalence of comorbidities was not statistically different between the AKA and BKA groups except that the BKA group had more patients with CKD who were dialysis-dependent than the AKA group (25% vs 4%, P = 0.03) [Table 1].
Operative characteristics are shown in [Table 2]. Forty-six percent of the amputations were performed in an urgent or semi-urgent setting for treatment of life-threatening limb disease. Forty percent were staged interventions requiring one or more additional procedure before the creation of the final amputation stump. Eighty-five percent underwent general anesthesia and 12% underwent spinal anesthesia. Amputations were equally distributed between both lower extremities; one patient required bilateral amputation during the same hospitalization as a result of worsening ischemia from multiple organ system failure following endovascular repair of aortic aneurysm. Operative characteristics were not statistically different when compared between the AKA and BKA groups. However, there was a trend toward a higher rate of staged procedures in the BKA group (50% vs 35%, P = 0.05) [Table 2].
Operative outcomes are shown in [Table 3]. Peri-operative mortality was 7% (BKA 8%, AKA 4%, P = 0.53). The rate of revision for wound failure was 10% (BKA 8%, AKA 12%, P = 0.60) and conversion from BKA to AKA occurred in one patient (2.7%). Three patients (5%) developed a non-fatal post-operative stroke. One of these patients (1.7%) had an additional non-fatal post-operative MI after BKA. All operative outcomes were not statistically different between the BKA and AKA groups [Table 3].
Long-term outcomes are shown in [Table 3]. The mean follow-up time was 39.7 ± 29.8 months. Through the course of the study, 50% of the patients died (BKA 56%, AKA 42%, P = 0.26). Thirty-eight percent of all patients developed a new MI, stroke, CHF or ESRD, the rates of which were comparable between AKA and BKA groups [Table 3]. Kaplan-Meier analysis showed the 1-year survival to be 73%, 3-year survival to be 61% and 5-year survival to be 54% in the whole cohort [Figure 1]. Survival was independent of level of amputation (P = 0.24) or urgency of the procedure (P = 0.51). Survival was significantly decreased by the presence of underlying chronic kidney disease (P = 0.04) but not by other comorbidities (history of MI, P = 0.79; metabolic syndrome, P = 0.64; diabetes mellitus, P = 0.56) [Figure 1]. The only variable that was a statistically significant predictor of mortality was CKD (risk ratio 2.27; 95% confidence interval 1.02-5.06; P = 0.0425; [Table 4]).
| Discussion|| |
We report a perioperative mortality of 7% after lower extremity amputation, with comparable results between the AKA and BKA groups. In this high-risk group of patients with extensive comorbid disease, 5-year survival was 54%. The presence of metabolic syndrome, history of myocardial infarction, level of amputation, or urgency of the procedure did not affect late survival. However, the presence of CKD prior to the amputation was associated with worse late survival [Table 4].
Multiple studies have evaluated specific comorbid diseases associated with reduced survival after major lower extremity amputation. Frequently, more than one comorbid condition have been identified, including congestive heart failure ,, , renal disease ,,, , cerebrovascular disease  , chronic obstructive pulmonary disease  , preoperative pneumonia,  diabetes mellitus  , age >75  , and admission through the emergency department.  In addition, AKA was previously found to be associated with worse survival compared to BKA. 
Metabolic syndrome has a high prevalence in our patient population (68%) similar to the one reported in patients with peripheral artery disease.  It is a pro-inflammatory and pro-thrombotic state accompanied by an increased risk for cardiovascular disease and type 2 diabetes mellitus.  At the endothelial level, it is associated with altered intima-media thickness and impaired myocardial perfusion which are independent predictors of adverse cardiovascular outcomes.  Two of the components of the metabolic syndrome, elevated fasting plasma glucose and microalbuminuria, are predictors of peripheral vascular disease.  In patients undergoing hemodialysis access placement, metabolic syndrome is associated with worse survival and secondary patency.  However, we did not find an association between metabolic syndrome and long-term mortality after major lower extremity amputation [Table 4]. The lack of association of metabolic syndrome with outcome after amputation may be related to several factors. First, patients with metabolic syndrome may be treated for their condition, including multiple medications that address the glucose as well as the lipid abnormalities. Second, metabolic syndrome may not be a statistically significant factor compared to others, such as CKD or cardiac disease that have significant effects on perioperative mortality. Third, our sample size may be insufficient to detect such an effect.
Several studies reported an association between renal disease and survival after amputation. Aulivola et al. reported significantly decreased survival among patients with diabetes mellitus, serum creatinine >2 mg/dL or ESRD. Interestingly, patients with elevated creatinine without ESRD had decreased survival similarly to those with ESRD.  Mayfield et al. reported on a large series from a veteran population and found that patients with renal disease have worse survival during the first year after amputation. Other predictors of worse mortality were proximal level of amputation, cerebrovascular disease and congestive heart failure.  Feinglass et al. reported on survival from the NSQIP database. Multiple preoperative comorbidities were associated with worse perioperative and late survival including BUN > 40 mg/dL and ESRD.  Dossa et al. reported a hospital mortality of 24%, a 1-year survival of 38% and a 2-year survival of 20% among patients with ESRD, advocating for aggressive foot care and patient education to prevent amputation.  How CKD contributes to worse survival is unclear. One study reported an association between preoperative CKD and postoperative malnutrition in patients undergoing open vascular surgery.  It might be of value to examine the nutritional status of this subgroup of patients and determine whether malnutrition is a common underlying factor.
Major lower extremity amputation is associated with significant mortality. Our peri-operative mortality of 7% is consistent with previously reported data ranging from 4 to 17%. ,,,, Peri-operative mortality was similar between the AKA and BKA groups, in contrast to previous reports of higher peri-operative mortality after AKA. , Post-operative surgical complications are not uncommon after major lower extremity amputation. We report a rate of wound revision and conversion that is lower than the rates reported in larger series where wound revision ranged between 13.2% and 15.4% and conversion ranged between 9% and 20%. ,, Also, we did not find a higher rate of local wound complications in the BKA group compared to the AKA group, which is different from previous reports. , The lower rate of local wound complications could be explained by the relatively high rate of staged procedures in our series (40%), since 46% of the procedures were performed in the setting of limb-threatening wet gangrene; two-stage amputation has fewer wound complications than one-stage amputation performed for wet gangrene. 
Our analysis is limited by the relatively small size of the population and retrospective nature of the study. It includes only veterans and lacks female patients who may have health characteristics different from the general population. , Due to the population size, we could not determine whether the observed decreased survival in patients with CKD is related to the subgroup of patients with ESRD. In addition, it is not known how the medical management of comorbid conditions evolved during the study period. Further studies are required to determine if better control of specific comorbid disease improves outcomes after lower extremity amputation.
In conclusion, major lower extremity amputation for ischemic disease is characterized by substantial perioperative mortality and morbidity. Metabolic syndrome is not associated with increased risk of adverse outcomes after lower extremity amputation. However, patients with chronic kidney disease constitute a sub-group of patients at higher risk of postoperative long-term mortality and may be a group to target for intervention to improve outcomes.
| References|| |
|1.||De Frang RD, Taylor LM Jr, Porter JM. Basic data related to amputations. Ann Vasc Surg 1991;5:202-7. |
|2.||Nowygrod R, Egorova N, Greco G, Anderson P, Gelijns A, Moskowitz A, et al. Trends, complications, and mortality in peripheral vascular surgery. J Vasc Surg 2006;43:205-16. |
|3.||Taylor SM, Kalbaugh CA, Blackhurst DW, Hamontree SE, Cull DL, Messich HS, et al. Preoperative clinical factors predict postoperative functional outcomes after major lower limb amputation: An analysis of 553 consecutive patients. J Vasc Surg 2005;42:227-35. |
|4.||Franco OH, Massaro JM, Civil J, Cobain MR, O'Malley B, D'Agostino RB Sr. Trajectories of entering the metabolic syndrome: The framingham heart study. Circulation 2009;120:1943-50. |
|5.||Protack CD, Bakken AM, Xu J, Saad WA, Lumsden AB, Davies MG. Metabolic syndrome: A predictor of adverse outcomes after carotid revascularization. J Vasc Surg 2009;49:1172-80. |
|6.||Davies MG, Saad WE, Bismuth J, Naoum JJ, Peden EK, Lumsden AB. Impact of metabolic syndrome on the outcomes of percutaneous renal angioplasty and stenting. J Vasc Surg 2010;51:926-32. |
|7.||Francis W, Renton CJ. Mobility after major limb amputation for arterial occlusive disease. Prosthet Orthot Int 1987;11:85-9. |
|8.||Sandnes DK, Sobel M, Flum DR. Survival after lower-extremity amputation. J Am Coll Surg 2004;199:394-402. |
|9.||Weiss JS, Dumas P, Cha C, Gusberg RJ, Dardik A. Safety of carotid endarterectomy in a high-risk population: Lessons from the va and connecticut. J Am Coll Surg 2006;203:277-82. |
|10.||Fitzgerald TN, Popp C, Federman DG, Dardik A. Success of carotid endarterectomy in veterans: High medical risk does not equate with high surgical risk. J Am Coll Surg 2008;207:219-26. |
|11.||Protack CD, Jain A, Vasilas P, Dardik A. The influence of metabolic syndrome on hemodialysis access patency. J Vasc Surg 2012;56:1656-62. |
|12.||Mayfield JA, Reiber GE, Maynard C, Czerniecki JM, Caps MT, Sangeorzan BJ. Survival following lower-limb amputation in a veteran population. J Rehabil Res Dev 2001;38:341-5. |
|13.||Feinglass J, Pearce WH, Martin GJ, Gibbs J, Cowper D, Sorensen M, et al. Postoperative and late survival outcomes after major amputation: Findings from the department of veterans affairs national surgical quality improvement program. Surgery 2001;130:21-9. |
|14.||Lavery LA, van Houtum WH, Armstrong DG, Harkless LB, Ashry HR, Walker SC. Mortality following lower extremity amputation in minorities with diabetes mellitus. Diabetes Res Clin Pract 1997;37:41-7. |
|15.||Dossa CD, Shepard AD, Amos AM, Kupin WL, Reddy DJ, Elliott JP, et al. Results of lower extremity amputations in patients with end-stage renal disease. J Vasc Surg 1994;20:14-9. |
|16.||Aulivola B, Hile CN, Hamdan AD, Sheahan MG, Veraldi JR, Skillman JJ, et al. Major lower extremity amputation: Outcome of a modern series. Arch Surg 2004;139:395-9. |
|17.||Gorter PM, Olijhoek JK, van der Graaf Y, Algra A, Rabelink TJ, Visseren FL; SMART Study Group. Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 2004;173:363-9. |
|18.||Vykoukal D, Davies MG. Vascular biology of metabolic syndrome. J Vasc Surg 2011;54:819-31. |
|19.||Di Pino A, Alagona C, Piro S, Calanna S, Spadaro L, Palermo F, et al. Separate impact of metabolic syndrome and altered glucose tolerance on early markers of vascular injuries. Atherosclerosis 2012;223:458-62. |
|20.||Wang J, Ruotsalainen S, Moilanen L, Lepisto P, Laakso M, Kuusisto J. Metabolic syndrome and incident end-stage peripheral vascular disease: A 14-year follow-up study in elderly finns. Diabetes care 2007;30:3099-104. |
|21.||Westvik TS, Krause LK, Pradhan S, Westvik HH, Maloney SP, Rutland R, et al. Malnutrition after vascular surgery: Are patients with chronic renal failure at increased risk? Am J Surg 2006;192:e22-7. |
|22.||Cruz CP, Eidt JF, Capps C, Kirtley L, Moursi MM. Major lower extremity amputations at a veterans affairs hospital. Am J Surg 2003;186:449-54. |
|23.||Abou-Zamzam AM Jr, Teruya TH, Killeen JD, Ballard JL. Major lower extremity amputation in an academic vascular center. Ann Vasc Surg 2003;17:86-90. |
|24.||Ploeg AJ, Lardenoye JW, Vrancken Peeters MP, Breslau PJ. Contemporary series of morbidity and mortality after lower limb amputation. Eur J Vasc Endovasc Surg 2005;29:633-7. |
|25.||Bunt TJ, Manship LL, Bynoe RP, Haynes JL. Lower extremity amputation for peripheral vascular disease. A low-risk operation. Am Surg 1984;50:581-4. |
|26.||Kazmers A, Perkins AJ, Jacobs LA. Major lower extremity amputation in veterans affairs medical centers. Ann Vasc Surg 2000;14:216-22. |
|27.||Keagy BA, Schwartz JA, Kotb M, Burnham SJ, Johnson G Jr. Lower extremity amputation: The control series. J Vasc Surg 1986;4:321-6. |
|28.||Nehler MR, Coll JR, Hiatt WR, Regensteiner JG, Schnickel GT, Klenke WA, et al. Functional outcome in a contemporary series of major lower extremity amputations. J Vasc Surg 2003;38:7-14. |
|29.||Nehler MR, Hiatt WR, Taylor LM Jr. Is revascularization and limb salvage always the best treatment for critical limb ischemia? J Vasc Surg 2003;37:704-8. |
|30.||Fisher DF Jr, Clagett GP, Fry RE, Humble TH, Fry WJ. One-stage versus two-stage amputation for wet gangrene of the lower extremity: A randomized study. J Vasc Surg 1988;8:428-33. |
[Table 1], [Table 2], [Table 3], [Table 4]
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