Abstract
ABSTRACT. Placement of a thigh graft is an option in hemodialysis patients who have exhausted all upper extremity sites for permanent vascular access. The outcome of thigh grafts has been reported only in retrospective studies. The outcomes of 409 grafts placed at a single institution during a 3.5-yr period were evaluated prospectively, including 63 thigh grafts (15% of the total). Information was recorded on surgical complications, dates of radiologic and surgical interventions, and date of graft failure. The technical failure rate was approximately twice as high for thigh grafts, as compared with upper extremity grafts (12.7 versus 5.8%; P = 0.046). Intervention-free survival was similar for thigh and upper extremity grafts (median, 3.9 versus 3.5 mo; P = 0.55). Thrombosis-free survival was also comparable for thigh and upper extremity grafts (median, 5.7 versus 5.5 mo; P = 0.94). Cumulative survival (time to permanent failure) was similar for thigh and upper extremity grafts (median, 14.8 versus 20.8 mo; P = 0.62). When technical failures were excluded, the median cumulative survival was 27.6 mo for thigh grafts and 22.5 mo for upper extremity grafts (P = 0.72). The frequency of angioplasty (0.28 versus 0.57 per year), thrombectomy (1.58 versus 0.94 per year), surgical revision (0.28 versus 0.18 per year), and total intervention rate (2.15 versus 1.70 per year) was similar between thigh and upper extremity grafts. Access loss as a result of infection tended to be higher for thigh grafts than for upper extremity grafts (11.1 versus 5.2%; P = 0.07). In conclusion, placement of thigh grafts should be considered a viable option among hemodialysis patients who have exhausted all options for a permanent vascular access in both upper extremities. E-mail mdallon@uab.edu
K/DOQI guidelines on vascular access recommend preferential placement of arteriovenous (A-V) fistulas in hemodialysis patients, with A-V grafts reserved for patients whose vascular anatomy precludes fistula placement (1). The rationale for this recommendation is that fistulas require substantially fewer interventions than do grafts to maintain long-term patency for dialysis (2). Notwithstanding these practice guidelines, the majority of hemodialysis patients in the United States continue to dialyze with grafts (3–5⇓⇓). A subset of patients experience multiple vascular access failures to the point that they exhaust options for further permanent vascular access in the upper extremities. In such patients, continued hemodialysis requires either placement of a thigh graft (interposed between the common femoral artery and the common femoral vein) or prolonged use of tunneled dialysis catheters. Given the frequent infectious and thrombotic complications of dialysis catheters (6), a thigh graft would seem to be the better option. However, the long-term outcomes of thigh grafts among hemodialysis patients has been reported only in retrospective series (7–12⇓⇓⇓⇓⇓), only two of which provided a comparison with a concurrent group of upper extremity grafts (8,11⇓).
Since 1996, we have been using an efficient, multidisciplinary approach to hemodialysis access (13). One of the hallmarks of this approach has been centralized scheduling of all vascular access procedures by a dialysis access coordinator, who maintains prospective, computerized records. This computerized database was used to track the outcomes, complications, and interventions for all vascular accesses in our dialysis population. The current study compared the short- and long-term outcomes of thigh grafts with those obtained in upper extremity grafts.
Materials and Methods
Patient Population
The University of Alabama at Birmingham (UAB) provides chronic dialysis to approximately 550 patients incenter hemodialysis patients at six dialysis units in metropolitan Birmingham. The demographics of our dialysis patient population are as follows: 29% of the patients are age 65 or older; 49% of the patients are female; 82% of the patients are black, and 18% are white; and 54% of the patients have diabetes. Despite a concerted effort to increase the proportion of patients who dialyze with fistulas (14), approximately 50% of patients used grafts during the study period. The medical care of these patients is provided by 10 clinical nephrologists, all full-time university faculty in the Division of Nephrology. All patient hospitalizations, surgical procedures, and radiologic procedures are done at UAB Hospital. Vascular access procedures are performed by the transplant surgeons and radiologic diagnostic tests and interventions for vascular access are performed by members of the Department of Radiology. Two full-time dialysis access coordinators schedule all dialysis access procedures with both surgery and radiology and serve as the liaison between the nephrologists, surgeons, radiologists, and dialysis staff, thereby providing consistency of communication (13).
Management of Dialysis Grafts and Their Complications
All A-V grafts were constructed by one of three experienced transplant surgeons during the 3.5-yr study period (January 1, 1999, to June 30, 2002). There was no overlap with a series of grafts previously reported from our institution (15). A concerted effort was made to attempt an A-V fistula, rather than a graft, whenever the surgeon believed that the vessels were suitable for fistula construction (14). A graft was constructed only when the patient had no suitable vessels for a fistula. The clinical assessment of the adequacy of the vessels was determined by the surgeon after reviewing the results of preoperative sonographic vascular mapping (2,14,16⇓⇓). We have previously reported that among patients who received their first vascular access, graft placement was required in only 23%. However, 61% of patients who received a secondary vascular access required A-V graft placement (14). Before placing a thigh graft, the surgeons performed a detailed clinical evaluation of the lower extremity circulation. In some cases, they ordered noninvasive studies or an arteriogram as part of the preoperative evaluation. When there was evidence for clinically significant peripheral vascular disease, the surgeons declined to place a thigh graft. A-V grafts were cannulated initially for dialysis 2 to 3 wk after their placement.
Clotted grafts were referred primarily to interventional radiology for mechanical thrombectomy in conjunction with angioplasty of hemodynamically significant stenotic lesions (17). When the thrombectomy was unsuccessful, a tunneled internal jugular dialysis catheter was placed under ultrasound guidance during the same procedure. Detailed definition of the relevant vascular anatomy permitted the surgeon to plan the optimal access procedure when the thrombectomy was unsuccessful. Surgical thrombectomy was performed in a small number of cases when thrombosis occurred within 1 mo of graft construction.
For decreasing the frequency of graft thrombosis, aggressive clinical surveillance for evidence of graft stenosis was implemented (13). Patients were referred to interventional radiology for a fistulogram when any of the following abnormalities was noted: (1) persistent elevation of dialysis venous pressures (DVP) at a low blood flow during initiation of dialysis, (2) prolonged bleeding from needle puncture sites in the graft, (3) unexplained progressive decrease in Kt/V, or (4) abnormal graft inspection and auscultation (18). We have previously reported that aggressive clinical monitoring of grafts and referral for a fistulogram when any one of these abnormalities was detected decreased the frequency of graft thrombosis by 60% (13).
Angioplasty of the stenotic lesion was attempted when it was thought to be hemodynamically significant (17). When the stenotic lesion was not amenable to angioplasty or failed to improve with angioplasty, the patient was referred for surgical revision (bypass graft). Grafts that clotted twice in 1 mo as a result of recurrent stenosis were also referred for surgical revision. Grafts were considered to have failed permanently when the vascular anatomy precluded surgical revision to restore graft patency. This could be due to a very long stenotic lesion in the graft or draining vein that did not respond to angioplasty, a venous occlusion in the very proximal upper extremity, a central vein lesion that could not be corrected radiographically, extensive graft pseudoaneurysm formation, or serious graft infection. Once a graft failed, the surgeons placed a new vascular access at a different site.
Statistical Analyses
All information regarding placement of new A-V grafts and subsequent graft complications and interventions was maintained prospectively in a computerized file maintained by the dialysis access coordinators (13). Consent to review the clinical database for research purposes was obtained from our Institutional Review Board. Our Institutional Review Board does not require an informed consent for such record review. Intervention-free graft survival was defined as the time interval from graft placement until the first graft intervention (thrombectomy, angioplasty, or surgical revision) or failure. Thrombosis-free graft survival was defined as the time from graft placement to first thrombosis or failure. Cumulative graft survival was defined as the time interval from initial graft placement until it could no longer be used for dialysis, regardless of how many interventions were required to maintain graft patency. Censored end points for analysis included death, transplant, loss to follow-up, and graft survival to the end of the study period (August 31, 2002). Survival distributions were plotted using the Kaplan-Meier method for intervention-free graft survival, thrombosis-free graft survival, and cumulative graft survival (19). Log rank tests were used to evaluate for statistical differences in survival distribution between thigh grafts and upper extremity grafts.
The patients’ medical records were also reviewed for the following demographic and clinical variables: age, gender, race, years on dialysis, number of previous vascular accesses, diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular disease, congestive heart failure, and history of a previous ipsilateral dialysis catheter. Comparison of the survival curves between upper extremity and thigh grafts was repeated after statistical adjustment for these multiple factors.
Graft salvage procedures were classified into one of three categories: thrombectomies, angioplasties, and surgical revisions. The frequency of graft interventions was calculated as the ratio between the number of interventions performed and the duration of follow-up (in graft-years). Because these frequencies were not normally distributed, Mann-Whitney U tests were used to compare intervention rates between thigh and upper extremity grafts (20).
Results
We analyzed the outcomes of all grafts placed in UAB dialysis patients during the 3.5-yr period from January 1, 1999 to June 30, 2002. A total of 409 grafts were placed: 346 in the upper extremities and 63 in the thighs. Thus, thigh grafts accounted for approximately 15% of all grafts placed during the study period. Table 1 summarizes the clinical characteristics of the patients who received grafts. Patients who received a thigh graft had a similar age, race, and gender distribution to those who received upper extremity grafts but were significantly less likely to have diabetes. Not surprising, patients who received a thigh graft had a significantly higher number of previous vascular accesses than those who received an upper extremity graft. Moreover, the mean time on dialysis at the time of access placement was >2 yr longer for thigh grafts than for upper extremity grafts. Approximately one third of patients with an upper extremity graft had had a previous ipsilateral dialysis catheter. The frequency of vascular disease was not significantly different between patients who received thigh grafts and those with upper extremity grafts, although peripheral vascular disease and cerebrovascular disease tended to be less frequent in the former group. Using multiple variable logistic regression, the likelihood of having a thigh graft was independently predicted by only two factors: absence of diabetes (odds ratio, 2.51 [1.36 to 4.66] and years on dialysis (odds ratio, 1.09 [1.02 to 1.15] per year on dialysis).
Table 1. Clinical features of patients with thigh versus upper extremity graftsa
The graft outcome was indeterminate in 17 cases (approximately 4% of the total) as a result of either early death or transfer to a dialysis unit outside of UAB within 1 wk of graft placement. The remaining 392 grafts were evaluated for subsequent outcomes. Twenty-eight graft placements (6.8% of the total) were technical failures (they could not be placed because of inadequate vessels during the surgical exploration or clotted immediately after the surgical anastomosis was completed). The technical failure rate was approximately twice as high for thigh grafts, as compared with upper extremity grafts (12.7 versus 5.8%; P = 0.046). Seven patients with mild peripheral vascular disease had a thigh graft placed after careful clinical assessment by the surgeon. No patient developed ischemic changes in the limb after thigh graft placement.
The intervention-free survival was similar for thigh and upper extremity grafts (Figure 1A). The median survival was 3.9 mo for thigh grafts and 3.5 mo for upper extremity grafts (hazard ratio, 0.91; 95% confidence interval, 0.67 to 1.25). Thrombosis-free survival was also comparable between the two graft locations (Figure 1B). The median survival was 5.7 mo for thigh grafts and 5.5 mo for upper extremity grafts (hazard ratio, 1.01 [0.72 to 1.43]). Finally, the cumulative survival was similar for thigh grafts and upper extremity grafts (Figure 2A). The median cumulative survival was 14.8 mo for thigh grafts and 20.8 mo for upper extremity grafts (hazard ratio, 1.11 [0.74 to 1.69]). When technical graft failures were excluded, the median cumulative survival was 27.6 mo for thigh grafts and 22.5 mo for upper extremity grafts (hazard ratio, 0.91 [0.56 to 1.49]; Figure 2B).
Figure 1. (A) Intervention-free graft survival comparing patients with thigh grafts with those with upper extremity grafts; P = 0.55 for the comparison between the two survival curves. (B) Thrombosis-free graft survival comparing patients with thigh grafts with those with upper extremity grafts; P = 0.94 for the comparison between the two survival curves. Technical failures and grafts that were never useable for dialysis are included in the analysis.
Figure 2. Cumulative graft survival comparing patients with thigh grafts with those with upper extremity grafts, with inclusion of technical failures (A), or after exclusion of technical failures (B); P = 0.62 and 0.72 for the comparison between the two survival curves in the two panels, respectively.
A comparison of the survival curves for thigh and upper extremity grafts was repeated after statistical adjustment for the following factors: age, gender, race, diabetes, peripheral vascular disease, coronary artery disease, cerebrovascular disease, congestive heart failure, years on dialysis, and history of previous ipsilateral dialysis catheter. There was no difference between intervention-free survival, thrombosis-free survival, or cumulative graft survival, whether technical failures were included or excluded (Table 2).
Table 2. Adjusted hazard ratios for outcomes of thigh grafts relative to upper extremity graftsa
Patients who received thigh grafts were much less likely to have diabetes than those who received upper extremity grafts (Table 1). It is possible that the outcomes of thigh grafts are actually worse than that of upper extremity grafts, but the difference is obscured by the lower prevalence of diabetes among patients who received a thigh graft. To evaluate this possibility, we compared the cumulative graft survival between patients with and without diabetes. The median cumulative survival was 22.5 and 19.4 mo, respectively (P = 0.79).
There were a total of 344 graft-years of follow-up in the present study. To maintain graft patency required a mean of 1.77 interventions, including 0.52 angioplasties, 1.04 thrombectomies, and 0.20 surgical revisions per graft-year. The frequency of salvage procedures was not significantly different between thigh and upper extremity grafts, although thigh grafts tended to undergo fewer angioplasties and more thrombectomies (Table 3).
Table 3. Frequency of graft interventionsa
In the course of the study, 171 grafts failed permanently, 146 (85%) as a result of thrombosis and 25 (15%) as a result of infection. Seven thigh grafts and 18 upper extremity grafts failed as a result of infection. Access loss as a result of infection tended to be higher for thigh grafts than for upper extremity grafts (11.1 versus 5.2%; P = 0.07). The infection rate was 0.13 per patient-year for thigh grafts and 0.07 for upper extremity grafts.
Discussion
We observed similar outcomes of thigh and upper extremity grafts in a well-defined hemodialysis population with prospective tracking of outcomes. This was true, whether one compared intervention-free survival (Figure 1A), thrombosis-free survival (Figure 1B), or cumulative graft survival (Figure 2A) between graft sites. Moreover, the graft outcomes did not differ when technical failures were excluded from the analysis (Figure 2B). Because this was not a randomized study, patients who received a thigh graft differed in several ways from those who received an upper arm graft (Table 1). However, even after adjusting for other demographic and clinical factors in the multivariable model, there was no significant difference in outcomes between thigh and upper extremity grafts (Table 2). Finally, with careful preoperative screening, no patient developed limb ischemia after placement of a thigh graft.
The long-term outcome of thigh grafts has been reported previously only in retrospective studies (Table 4). Cumulative graft survival in the present study was similar to that found by Khadra et al. (11) but lower than that in three other series (7,9,12⇓⇓). In a retrospective comparison, Zibari et al. (8) reported a mean patency of 1.5 yr for thigh grafts, as compared with 1.9 yr for upper extremity grafts. Most of the retrospective studies do not state whether technical failures or graft loss to infection were included in calculation of cumulative survival. Exclusion of these events would suggest an overly optimistic graft outcome. Thus, for example, Tashjian et al. (12) observed an 83% thrombosis-free survival at 2 yr (censoring for loss as a result of infection) and a 76% infection-free survival at 2 yr (censoring for loss as a result of thrombosis). Combining the two events would yield an overall cumulative graft survival of 59% at 2 yr.
Table 4. Outcomes of thigh grafts in the literaturea
Diabetes was less common among patients who received thigh grafts than in those with upper extremity grafts. This difference is likely due to the shorter dialysis patient survival in individuals with than without diabetes (21) and the longer duration on dialysis before a patient would be considered for a thigh graft (Table 1). In other words, fewer dialysis patients with diabetes live long enough to exhaust all options for upper extremity vascular access. Nevertheless, the difference in frequency of diabetes was unlikely to be a confounding variable affecting the relative survival of thigh and upper extremity grafts, given the similar cumulative graft survivals that we observed in patients with and without diabetes.
Both thigh and upper extremity grafts required a high frequency of elective angioplasty, thrombectomy, and surgical revision to maintain their long-term patency for dialysis (Table 3). The major cause of graft failure is thrombosis as a result of occlusion of the venous anastomosis, draining vein, or central vein (22). Myointimal hyperplasia is the initial pathophysiologic event leading to graft stenosis. In the absence of prophylactic measures to prevent myointimal hyperplasia, most grafts develop progressive stenosis. When the stenosis is not detected and corrected in a timely manner, grafts typically clot and require thrombectomy to restore their patency. A number of studies have found that an ongoing surveillance program for graft stenosis and timely intervention with angioplasty or surgical revision can substantially reduce (but not eliminate) the frequency of graft thrombosis (13,23–26⇓⇓⇓⇓). In the present study, thigh grafts tended to have less frequent angioplasties and more frequent thrombectomies than did upper extremity grafts (Table 3). These differences suggest that clinical monitoring for graft stenosis may be less sensitive for thigh grafts than for upper extremity grafts, although this specific question has not been addressed in the medical literature.
Because of their proximity to the groin, thigh grafts might be thought to be more prone to infection than upper extremity grafts. In fact, we found a trend (P = 0.07) of higher risk of infection with thigh grafts. The frequency of thigh graft infection that we observed was in the low end of that observed in several previous retrospective studies (Table 4). In a retrospective comparison, Zibari et al. (8) reported an infection in 12.5% of thigh grafts versus 16.7% of upper extremity grafts.
In conclusion, the performance of thigh grafts is comparable to that of upper extremity grafts. Despite a significantly higher technical failure rate, intervention-free survival, thrombosis-free survival, and cumulative survival were similar between thigh and upper extremity grafts. The thigh graft infection rate of 0.13 per patient-year that we observed is far lower than that reported for tunneled dialysis catheters (0.7 to 2.0 per patient-year, or 2.0 to 5.5 per 1000 patient-days) (27–32⇓⇓⇓⇓⇓). The thigh graft thrombosis rate of 1.58 per patient-year compares favorably to that reported for tunneled dialysis catheters (3.0 to 3.2 per patient-year, or 8.1 to 8.8 per 1000 patient-days) (28,33⇓). The cumulative thigh graft survival rate at 1 yr (62%) is substantially higher than the corresponding 9% rate reported for tunneled dialysis catheters (34). Finally, the median dialysis blood flow delivered by grafts is substantially higher than that obtained with catheters, thereby enhancing dialysis adequacy (6). For all of these reasons, placement of thigh grafts should be considered a viable option among hemodialysis patients who have exhausted all options for a permanent vascular access in both upper extremities and is certainly far preferable to the long-term use of a tunneled dialysis catheter. Because our results reflect the outcomes at a single institution, they may not generalize to all dialysis centers.
Acknowledgments
This study was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant 1 K24 DK59818-01 to Dr. Allon. We thank our dialysis access coordinators Donna Carlton and Lisa Bimbo for maintaining the computerized database of access procedures.
- © 2003 American Society of Nephrology