Approximately 8.5 million individuals in the United States are affected by peripheral artery disease (PAD). The annual incidence of PAD is 2.8% and the prevalence rate is 12.3%. In patients with the most severe forms of PAD, amputation of the lower extremities may be required. Patients with PAD and end-stage renal disease (ESRD) receiving dialysis are at high risk of amputation, due, in part, to the high prevalence of traditional risk factors such as diabetes and hypertension and ESRD-related risk factors including chronic inflammation and uremia. Dialysis initiation is also an independent risk factor for amputation.
A recent analysis of data from the general Medicare population found a 45% decrease in rates of lower extremity amputation from 1996 to 2011. Possible explanations for the decrease in rates include better screening for PAD and improved vascular care, particularly for patients with diabetes. There are few data available on whether there had been a similar improvement in rates of lower extremity amputation in patients with ESRD who receive dialysis.
Douglas Franz, MD, MPH, and colleagues utilized the national ESRD registry to examine the rates of lower extremity amputation from 2000 to 2014 for patients with ESRD receiving dialysis. The researchers sought to determine whether the rates were associated with patient characteristics or comorbidities. Regional differences in amputation practices and 1-year mortality rates following lower extremity amputation were also assessed. Results were reported online in JAMA Internal Medicine [doi:10.1001/jamainternmed.2018.2436].
The retrospective study utilized records from the US Renal Data System for all patients initiating hemodialysis or peritoneal dialysis between January 1, 1996, and October 1, 2004 (n=3,700,902). Due to the accrual of prevalent patients with time, the size of each annual cohort increased progressively, as did dialysis vintage. Exclusion criteria were age <18 years or >110 years at incident ESRD, Centers for Medicare & Medicaid Services form 2728 missing or filed >45 days following dialysis initiation, or missing data on race or sex. Patients who recovered kidney function within 365 days of dialysis initiation were also excluded.
The primary outcome of interest was the number of lower extremity amputations per 100 patient-years for each cohort year, identified using International Classification of Diseases, Ninth Edition procedure codes and Current Procedure Terminology, 4th Revision codes. Amputations were classified as major (above- or below-knee) or minor (below-ankle). Only the highest-level amputation per patient per calendar year was included. A secondary outcome was 1-year mortality following lower extremity amputation (applied only to those patients in each annual cohort who underwent amputation in 2000 through 2013).
In each annual cohort, there were fewer women (47.5% in 2000, 46.2% in 2005, 44.9% in 2010, and 44.0% in 2014), more than half of the participants were white (58.1% in 2000, 56.9% in 2005, 56.9% in 2010, and 56.7% in 2014), and a relatively small proportion were employed (13.9% in 2000, 15.1% in 2005, 16.1% in 2010, and 16.5% in 2014). Over time, the proportion of patients with diabetes and hypertension increased, and the proportion of patients with coronary artery disease and recognized PAD decreased.
From 2000 to 2014, the adjusted rate of all lower extremity amputations decreased, from 5.42 per 100 person-years (95% confidence interval [CI] 5.28-5.56) to 2.66 per 100 person-years (95% CI, 2.59-2.72). The relative decrease over that time period was 51.0%. The adjusted rate of above-knee amputations decreased by 65.0% and the adjusted rate of below-knee amputations decreased by 58.5%; the adjusted rate of below-ankle amputations decreased by 25.9% during the period 2000 to 2014.
During the study period, the adjusted rate of any lower extremity revascularization procedure decreased from 1.63 per person-years (95% CI, 1.55-1.71) in 2000 to 1.28 per person-years (95% CI, 1.24-1.33) in 2014, a decrease of 21.5%. The adjusted rates of surgical bypass decreased by 56.4% (95% CI, 52.5%-60.0%); the adjusted rate of endovascular revascularization increased by 37.0% (95% CI, 25.5%-49.7%) during the study period.
The adjusted amputation rate for patients with diabetes decreased from 8.65 per 100 person-years (95% CI, 8.41-8.88) in 2000 to 4.09 per 100 person-years (95% CI, 3.99-4.19) in 2014, a decrease of 52.8%. The adjusted amputation rate for patients without diabetes also decreased during that time period, from 1.43 per 100 person-years (95% CI, 1.31-1.54) to 0.74 per 100 person-years (95% CI, 0.69-0.79). The amputation rate decreased more quickly for patients with diabetes compared with patients without diabetes (P<.001 for interaction). However, the rates of amputation in patients with diabetes remained >5 times as high as those without diabetes during the study period.
Patients without diabetes or hypertension had lower adjusted rates of amputation compared with that of the overall cohort: 1.03 per 100 person-years (95% CI, 0.78-1.27) in 2000 and 0.50 100 person-years (95% CI, 0.37-0.63) in 2014, a decrease of 51.1%.
In age-based analyses, adjusted amputation rates per 100 person-years were similar in 2000 for patients <65 years of age (5.38; 95% CI, 5.18-5.57) compared with patients ≥65 years of age (5.25; 95% CI, 5.06-5.45). Over time, however, the adjusted rates of amputation decreased less rapidly for patients <65 years of age than for patients ≥65 years of age: in 2014, amputation rates were 2.92 (95% CI, 2.84-3.00) per 100 person-years versus 2.25 (95% CI, 2.16-2.35) per 100 person-years, respectively (P=.005 for interaction).
Adjusted rates for men were higher than for women in 2000; the rates for both men and women decreased similarly with time (P=.06 for interaction). Among all hospital referral regions, the rates of lower extremity amputation generally decreased during the study period; however, regional variability in rates of amputation persisted with time, despite adjustment for differences in patient demographics or comorbid conditions.
During the study period, the adjusted 1-year mortality rates following lower extremity amputation in the study population decreased by 17% (95% CI, 14%-20%), from 52.2% (95% CI, 50.9%-53.4%) in 2000 to 43.6% (95% CI, 42.5%-44.8%) in 2013.
Study limitations cited by the authors included the inability to determine laterality of amputation from billing claims, depending on the Medical Evidence Report to determine comorbid conditions, and limiting the analysis to patients with ESRD with Medicare Parts A and B as primary coverage.
In conclusion, the researchers said, “Although rates of lower extremity amputations among US patients with ESRD who receive dialysis decreased by 51% during a recent 15-year period, mortality rates remained high, with nearly half of patients dying within a year after lower extremity amputation. Our results highlight the need for more research on ways to prevent lower extremity amputation in this extremely high-risk population.”
- Patients with end-stage renal disease who receive dialysis are at high risk of lower extremity amputation. Researchers conducted a study to examine rates of lower extremity amputation in this patient population from 2000 through 2014.
- Overall, the rates of lower extremity amputation decreased by 51% during the study period; the decrease was driven mainly by a decrease in major amputations (above- or below-knee).
- The mortality rates at 1-year following lower extremity amputation remained high; nearly half of the patients who underwent the procedure died within a year after amputation.