Chronic Kidney Disease and Outcomes of Lower Extremity Revascularization for Peripheral Artery Disease

Abstract

Background & aims:

Renal disease is a risk factor for peripheral artery disease (PAD), yet its impact on outcomes after lower extremity (LE) revascularization is not well established. We aimed to characterize the association between chronic kidney disease (CKD) and/or end stage renal disease (ESRD) and post-procedural outcomes in PAD patients undergoing LE revascularization in the United States.

Methods:

Adults age ≥18 years undergoing surgical or endovascular LE revascularization for PAD with and without CKD or ESRD were identified from the 2014 Nationwide Readmissions Database. Major adverse cardiovascular events (MACE), defined as a composite of death, myocardial infarction or ischemic stroke, were identified for patients with and without renal disease. All-cause hospital readmissions within 6 months of discharge were determined for all survivors.

Results:

Among 39,441 patients with PAD hospitalized for LE revascularization, 10,530 had renal disease (26.7%), of whom 69% had CKD without ESRD and 31% had ESRD. Patients with renal disease were more likely to have MACE after LE revascularization (5.2% vs. 2.5%; adjusted OR [aOR] 1.74, 95% CI 1.40–2.16), require LE amputation (26.1% vs. 12.2%; aOR 1.33, 95% CI 1.19–1.50), and require hospital readmission within 6 months (61.0% vs. 43.6%; adjusted HR [aHR] 1.38, 95% CI 1.28–1.48) compared to those without renal disease.

Conclusions:

Renal disease is common among patients undergoing LE revascularization for PAD and was independently associated with in-hospital MACE, LE amputation, and hospital readmission within 6 months. Additional efforts to improve outcomes of patients with renal disease and PAD requiring LE revascularization are necessary.

Graphical Abstract

Introduction

Peripheral artery disease (PAD) affects ~8.5 million individuals in the United States age ≥40 years and can present with symptoms of claudication, rest pain, or ischemic tissue loss with ulcerations and gangrene.^1–3 Lower extremity revascularization is frequently performed to improve morbidity and quality of life in patients with symptomatic PAD.^{1, 3, 4} Chronic kidney disease (CKD) is an important risk factor for PAD. Patients with CKD have up to a two-fold increased risk of incident PAD, with the greatest risk at the lowest glomerular filtration rates.^{5, 6} Although CKD is independently associated with adverse clinical outcomes in a number of disease states,⁷ data on the impact of CKD and end stage renal disease (ESRD) on short-term cardiovascular outcomes after endovascular and surgical lower extremity revascularization for PAD are limited. In a recent analysis of patients with critical limb ischemia (CLI), CKD was independently associated with 30-day hospital readmission.⁸ Unfortunately, this study was restricted to PAD patients with CLI, approaches to LE revascularization and post-procedural outcomes were not reported for subgroups of patients with and without renal disease, only 30-day hospital readmissions were evaluated, and patients with renal disease with and without ESRD were grouped together. Other studies evaluating the associations between CKD and outcomes in patients with PAD have been small, and limited to patients undergoing endovascular lower extremity revascularization.^9–11 Therefore, we aimed to characterize the association between CKD with and without ESRD and post-procedural outcomes in all patients undergoing open or endovascular lower extremity revascularization for PAD from a large database of hospital admissions from the United States.

Materials and methods

Data sources

Patients undergoing surgical or endovascular lower extremity revascularization for PAD were identified from the 2014 Nationwide Readmissions Database (NRD). The NRD is a publicly available database from the United States Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project. Each year, the NRD combines data from 22 geographically disperse state inpatient databases to create an estimate of all hospitalizations and discharges from academic and community hospitals. that represent approximately 50% of the total US resident population and all US hospitalizations. The NRD includes in-hospital International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9) diagnosis and procedure codes and scrambled linkage identifiers that can be used to track individual patients across hospitalizations within each state database.

Study population

Adults age ≥18 years who were hospitalized for endovascular or surgical lower extremity revascularization between January 1, 2014 and June 30, 2014 were identified using ICD-9 diagnosis and procedure codes. All patients undergoing revascularization were required to have a diagnosis of PAD or coding for symptoms consistent with PAD, such as claudication, as previously described (Supplemental Table 1).^{8, 12} Critical limb ischemia was defined by ICD-9 diagnosis codes for ulcers or gangrene in combination with a diagnosis of PAD. Among patients with >1 admission for lower extremity revascularization during the calendar year, only the first hospitalization for lower extremity revascularization was included in the analysis. Patients who were discharged in July 2014 or later were excluded from the analysis to ensure complete 6-month follow-up for all individuals.

Demographics and clinical comorbidities were defined by relevant ICD-9 diagnosis codes and AHRQ Elixhauser comorbidities for all patients. Renal disease was defined as the presence of any CKD or ESRD, as previously described.^{13, 14} Chronic kidney disease was defined by ICD-9 diagnosis codes for CKD stages I-V (585.1–585.5 and 585.9). End stage renal disease was defined by ICD-9 diagnosis codes for end stage renal disease (585.6) or based on ICD-9 procedure codes for peritoneal dialysis (54.98) or hemodialysis (39.95), excluding dialysis performed for AKI (ICD-9 diagnosis codes 584.5–584.9). Patients without any ICD-9 codes for CKD or ESRD were assigned to the group without renal disease. The use of ICD-9 diagnosis codes to identify patients with chronic kidney disease has been previously validated.¹⁵

Outcomes after lower extremity revascularization

Major adverse cardiovascular events (MACE) during hospitalization for lower extremity revascularization were determined. MACE was defined as a composite of all-cause death, acute myocardial infarction (ICD-9 diagnosis codes 410.01 to 410.61, 410.81, 410.71, and 410.91), and acute ischemic stroke (ICD-9 diagnosis codes 433.x1, 434.x1, 436, and 437.1) (Supplemental Table 1). Major adverse limb events (MALE) were defined as a composite of critical limb ischemia or major amputation during hospital readmission.¹⁶ Other endpoints included the individual endpoints of the MACE composite, lower extremity amputation, bleeding, and acute kidney injury (Supplemental Table 1). All-cause hospital readmission within 6 months was determined for all patients. If patients had ≥1 readmission after the index lower extremity revascularization procedure, only the first re-hospitalization was included in the analysis. Hospital admissions were classified into clinical categories by primary diagnosis code using the Healthcare Cost and Utilization Project’s Body System Indicator.

Statistical analysis

Patient demographics, comorbidities, and outcomes were analyzed in patients with and without renal disease, defined as CKD or ESRD. Categorical variables were reported as percentages and were compared by χ² tests. Continuous variables were reported as means with the standard error of measurement (SEM) and were compared using linear regression. Multivariable logistic regression models were used to estimate odds ratios associated with renal disease and adjusted for patient demographics and clinical covariates. Models included age, sex, tobacco use, obesity, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, prior PCI or CABG, heart failure, prior stroke, malignancy, anemia, chronic liver disease, chronic pulmonary disease, urgent or emergent hospitalization for lower extremity revascularization and approach to revascularization. Time-to-event Cox proportional hazards analyses were used to examine the association between CKD or ESRD and re-hospitalization at 6 months, while controlling for potential demographic and clinical confounders. In order to confirm the findings of the primary analysis, we performed propensity matching to account for differences in baseline characteristics, clinical presentations, and procedural approaches in cohorts of patients with and without renal disease. Patients were matched on the basis of age, sex, hypertension, hyperlipidemia, diabetes mellitus, tobacco use, obesity, coronary artery disease, prior PCI and CABG, malignancy, anemia, clinical presentation with critical limb ischemia, and surgical versus endovascular revascularization. We also performed key subgroup analyses of patients by revascularization strategy (surgical versus endovascular revascularization) and indication for revascularization (critical limb ischemia versus claudication). To determine national incidence estimates, complex survey analysis methods that incorporate sampling weights, clustering, and strata were used. Statistical analyses were performed using SPSS 25 (IBM SPSS Statistics, Armonk, NY). Statistical tests are two-sided and P-values <0.05 were considered to be statistically significant. The NRD is a de-identified, publicly available dataset, and the study was exempt from institutional board review.

Patient involvement

Patients were not involved in developing the research question, study design, outcome measures, or study conduct. No patients provided input into data analysis or the interpretation of results. There are no plans to disseminate the results to study participants. No patients served as authors or contributors to this work.

Results

Baseline characteristics

A total of 39,441 patients were hospitalized for endovascular or surgical revascularization for lower extremity PAD during the study period. Of these, 10,530 had renal disease (26.7%), of whom 7,281 had CKD without ESRD (69%) and 3,250 had ESRD (31%). Patients with renal disease were older (71 vs. 68 years, p<0.001), and were more likely to have cardiovascular risk factors, coronary artery disease, and heart failure when compared to patients without renal disease (Table 1). Non-cardiovascular medical comorbidities, including anemia, chronic pulmonary disease, and liver disease, were also more common in PAD patients with versus without renal disease. Among patients with renal disease, those with ESRD were younger, more likely to have cardiovascular comorbidities, heart failure, chronic pulmonary disease, and anemia in comparison to patients with CKD without ESRD (Table 1).

Table 1.

Baseline characteristics of index hospitalization

	All patients undergoing LE revasculariz ation (n=39441)	No CKD (n=28911)	Any CKD/ESRD (n=10530)	p-value	CKD (n=7281)	ESRD (n=3250)	p-value
Age, years (SEM)	69 (0.151)	68 (0.168)	71 (0.215)	<0.001	73 (0.232)	66 (0.336)	<0.001
Female sex	15366 (39.0%)	11369 (39.3%)	3997 (38.0%)	0.13	2763 (37.9%)	1234 (38.0%)	0.29
Obesity	3990 (10.1%)	2512 (8.7%)	1478 (14.0%)	<0.001	1056 (14.5%)	422 (13.0%)	0.22
Tobacco current or former use	20408 (51.7%)	16820 (58.2%)	4128 (39.2%)	<0.001	3070 (42.2%)	1058 (32.6%)	<0.001
Hypertension	31963 (81.0%)	22185 (76.7%)	9778 (92.9%)	<0.001	6682 (91.8%)	3096 (95.3%)	<0.001
Hyperlipidemia	22080 (56.0%)	16077 (55.6%)	6003 (57.0%)	<0.001	4424 (60.8%)	1579 (48.6%)	<0.001
Diabetes mellitus	20038 (50.8%)	12551 (43.4%)	7487 (71.1%)	<0.001	4907 (67.4%)	2580 (79.4%)	<0.001
Coronary artery disease	18448 (46.8%)	12302 (42.6%)	6146 (58.4%)	<0.001	4229 (58.1%)	1917 (59.0%)	0.60
Prior PCI	4354 (11.0%)	2972 (10.3%)	1382 (13.1%)	<0.001	976 (13.4%)	406 (12.5%)	0.48
Prior CABG	6450 (16.4%)	4310 (14.9%)	2140 (20.3%)	<0.001	1540 (21.2%)	600 (18.5%)	0.025
Heart failure	742 (1.9%)	287 (1.0%)	455 (4.3%)	<0.001	248 (3.4%)	207 (6.4%)	<0.001
Prior stroke	3913 (9.9%)	2730 (9.4%)	1183 (11.2%)	0.002	833 (11.4%)	350 (10.8%)	0.51
Malignancy	774 (2.0%)	605 (2.1%)	169 (1.6%)	0.091	123 (1.7%)	46 (1.4%)	0.48
Anemia	8839 (22.4%)	4170 (14.4%)	4669 (44.3%)	<0.001	2549 (35.0%)	2120 (65.2%)	<0.001
Chronic pulmonary disease	10203 (25.9%)	7683 (26.6%)	2520 (23.9%)	<0.001	1912 (26.3%)	608 (18.7%)	<0.001
Liver disease	708 (1.8%)	436 (1.5%)	272 (2.6%)	<0.001	165 (2.3%)	107 (3.3%)	0.053

Index hospital admission and lower extremity revascularization

Patients with renal disease were more likely to present with CLI as the indication for lower extremity revascularization in comparison to patients without renal disease (87.3% vs. 68.4%, p<0.001). Similarly, patients with ESRD were more likely to have CLI as an indication for revascularization than patients with CKD without ESRD (95.6% vs. 83.6%, p<0.001), (Figure 1 and Supplemental Table 2)

Figure 1.

Characteristics of the index hospitalization by CKD/ESRD status. Characteristics of the index hospitalization by CKD/ESRD status including indication for revascularization (A) and endovascular versus surgical approach to revascularization (B)

Overall, surgical revascularization was performed more frequently than endovascular revascularization in patients hospitalized for lower extremity revascularization (60.3% vs. 39.7%, p<0.001). Patients with renal disease were more likely to undergo endovascular revascularization (55.1% vs. 34.1%, p<0.001) than patients without renal disease. Patients with ESRD were more likely to undergo endovascular revascularization than those with CKD without ESRD (62.3% vs. 51.8%, p<0.001), (Figure 1 and Supplemental Table 2).

Outcomes during index hospitalization

During the index hospitalization for lower extremity revascularization, MACE occurred in 3.3% of all patients, with a greater frequency in patients with renal disease compared to those without renal disease (5.2% vs. 2.5%, p<0.001). After multivariable adjustment for demographics and clinical covariates patients with PAD and renal disease had a 74% higher odds of MACE than those with PAD without renal disease (adjusted OR [aOR] 1.74, 95% CI 1.40–2.16), (Table 2). Among patients with renal disease, the frequency of MACE was not different among patients with ESRD and those with milder forms of CKD (5.8% vs. 5.0%, p=0.30). In hospital death occurred in 1.5% of PAD patients after lower extremity revascularization and was also more common in patients with renal disease (2.3% vs. 1.2%, p<0.001; aOR 1.90, 95% CI 1.38–2.61) than those without renal disease. Renal disease was significantly associated with acute myocardial infarction (aOR 1.61, 95% CI 1.17–2.23) but was not associated with a post-procedural ischemic stroke (aOR 1.57, 95% CI 0.95–2.59). Associations between renal disease and cardiovascular events were consistent in subgroups of patients who underwent surgical and endovascular lower extremity revascularization (Supplemental Tables 3 and 4), and in subgroups with critical limb ischemia and claudication (Supplemental Tables 5 and 6).

Table 2.

Outcomes during index hospitalization for lower extremity revascularization

	All patients undergoing LE revascularization (n=39441)	No CKD (n=28911)	Any CKD/ESRD (n=10530)	p-value	aOR (95% CI)	CKD (n=7281)	ESRD (n=3250)	p-value	aOR (CKD vs. Normal)	aOR (ESRD vs. Normal)
MACE (death/AMI/stroke)	3.3%	2.5%	5.2%	<0.001	1.74 (1.40–2.16)	5.0%	5.8%	0.30	1.54 (1.22–1.94)	2.00 (1.36–2.96)
In-hospital death	1.5%	1.2%	2.3%	<0.001	1.90 (1.38–2.61)	1.7%	3.5%	<0.001	1.31 (0.90–1.89)	3.78 (2.39–5.96)
Acute myocardial infarction	1.6%	1.3%	2.7%	<0.001	1.61 (1.17–2.23)	2.9%	2.2%	0.28	1.61 (1.15–2.24)	1.16 (0.6–2.24)
Acute ischemic stroke	0.5%	0.4%	0.8%	0.019	1.57 (0.95–2.59)	0.8%	0.7%	0.66	1.63 (0.95–2.79)	1.35 (0.6–3.05)
Lower extremity amputation	15.5%	12.2%	26.1%	<0.001	1.33 (1.19–1.50)	21.6%	36.0%	<0.001	1.18 (1.04–1.34)	1.58 (1.30–1.91)
Bleeding	17.7%	14.8%	25.7%	<0.001	1.42 (1.27–1.59)	24.3%	28.6%	0.005	1.40 (1.23–1.59)	1.35 (1.13–1.61)
Transfusion of PRBCs	14.6%	11.8%	22.4%	<0.001	1.50 (1.33–1.69)	21.2%	25.1%	0.011	1.49 (1.30–1.69)	1.38 (1.14–1.69)
Acute kidney injury	10.9%	6.3%	23.2%	<0.001	3.27 (2.86–3.74)	33.6%	0	<0.001	5.65 (4.95–6.45)	N/A

Lower extremity amputation occurred more frequently in patients with PAD and renal disease undergoing lower extremity revascularization compared with those without renal disease (26.1% vs. 12.2%, p<0.001; aOR 1.33, 95% CI 1.19–1.50). Bleeding was common during hospitalization for lower extremity revascularization and was more common in patients with renal disease versus patients without renal disease (25.7% vs. 14.8%, p<0.001; aOR 1.42 95% CI 1.27–1.59). Increases in bleeding associated with renal disease were consistent in patients undergoing both surgical and endovascular revascularization. Patients with PAD and renal disease hospitalized for lower extremity revascularization were more likely to develop acute kidney injury compared with PAD patients without renal disease (23.3% vs. 6.3%, p<0.001; aOR 3.27, 95% CI 2.86–3.74).

Frequency and Indication for Hospital Readmission

Among the 38,864 individuals who were discharged alive after a lower extremity revascularization procedure, 19,022 patients (48.9%) were readmitted within 6 months. The cumulative incidences of readmission in patients with and without renal disease are shown in Figure 2. A substantially greater proportion of patients with renal disease were re-hospitalized within 6 months after revascularization compared to those without renal disease (61.0% vs. 43.6%, p<0.001; adjusted HR [aHR] for readmission 1.38, 95% CI 1.28–1.48). Among patients with renal disease, a greater proportion of patients with ESRD were readmitted compared to those with CKD without ESRD (71.0% vs. 56.6%, p<0.001; aHR 1.42 95% CI 1.27–1.60; Figure 2).

Figure 2.

Cumulative incidence of hospital readmission within 6 months following in-hospital surgical or endovascular lower extremity revascularization, in patients with and without renal disease (A) and with no CKD, CKD without ESRD, and ESRD (B).

A total of 15.5% of patients who survived to discharge after the index hospitalization were readmitted with MALE within 6 months of the index LE revascularization. Patients with renal disease were more likely to be rehospitalized with MALE than those without renal disease (21.1% vs. 13.5%, p<0.001; aHR 1.34, 95% CI 1.17–1.54). Patients with ESRD were more likely to be readmitted with MALE than patients with CKD without ESRD (28.0% vs. 18.0%, p<0.001; aHR 1.51, 95% CI 1.22–1.85).

The frequency of hospital readmissions by indication among patients with and without renal disease are shown in Figure 3. Patients with renal disease and PAD undergoing LE revascularization were more likely to be readmitted with circulatory system disorders than those without renal disease undergoing LE revascularization (20.4% vs. 15.8%, p<0.001). Indications for hospital readmission over time are shown in Figure 4 and in Supplemental Figure 1A and B. Among patients who were readmitted, 35.4% had primary disorders of the circulatory system as classified by the Healthcare Cost and Utilization Project’s Body System Indicator, 25.4% had a disorder not neatly classified by body system (including ‘ill-defined conditions’, ‘injury or poisoning’, or ‘factors influencing health status and contact with health services’), and 11.3% had endocrine, nutritional or metabolic disorders. Overall, the most common primary diagnosis codes associated with hospital readmission after lower extremity revascularization were related to atherosclerosis-associated gangrene (7.8% of readmissions), postoperative infection (5.4%), or complications due to a vascular device, implant, or graft (5.3%). Primary ICD-9 diagnosis codes with the greatest frequency during hospital readmission after hospitalization for lower extremity revascularization are shown in Supplemental Table 7.

Figure 3.

Frequency of hospital readmission by indication after lower extremity revascularization in patients with and without renal disease.

Figure 4.

Indications for hospital readmission after lower extremity revascularization over time.

Outcomes during hospital readmission

Among the 19,022 patients with ≥1 readmission within 6 months of lower extremity revascularization, MACE occurred in 8.3% of hospital readmissions. The incidence of MACE was greater in patients with renal disease versus those without (10.5% vs. 7.2%, p<0.001; aOR 1.31, 95% CI 1.07–1.60). Death during rehospitalization occurred in 3.3% of patients overall, MI occurred in 4.3% of readmissions, and stroke occurred in 1.6%. Lower extremity amputation was reported in 19.6% of patients who were re-hospitalized, bleeding occurred in 19.9% of cases, and acute kidney injury was diagnosed in 17.4% of cases. The frequency of events during rehospitalization in patients with and without renal disease are shown in Supplemental Table 8.

Propensity matched analysis

In a propensity-matched analysis, 4,255 individuals with any CKD (with or without ESRD) were matched to 4,255 individuals without CKD (unweighted counts). Matched patients with CKD had a higher frequency of MACE during the index admission (5.5% vs. 3.3%, p<0.001) and were more likely to be readmitted within 6 months of discharge after lower extremity revascularization (59.6% vs. 50.3%, p<0.001) than patients without CKD. In a separate propensity-matched analysis among patients with CKD, 1,336 individuals with ESRD were matched to 1,336 individuals with CKD without ESRD (unweighted counts). Patients with ESRD had a numerically higher incidence of MACE during the index admission for LE revascularization than patients with CKD without ESRD (6.1% vs. 4.4%, p=0.068). Matched patients with ESRD were more likely to be readmitted within 6 months of discharge after lower extremity revascularization than patients with CKD without ESRD (70.9% vs. 60.6%, p<0.001).

Discussion

In a nationally representative cohort of patients with PAD hospitalized for endovascular or surgical lower extremity revascularization, 1.5% died during the index hospitalization and 48% were readmitted within six months. A quarter of patients undergoing revascularization for PAD had chronic renal disease, and these patients had a greater burden of cardiovascular comorbidities than patients with normal renal function. During the index hospitalization and hospital readmissions following revascularization, risks of cardiovascular events, lower extremity amputation, and bleeding were greater in patients with renal disease compared to those without renal disease. Additionally, the severity of renal disease was associated with adverse outcomes in patients with PAD undergoing revascularization. In-hospital death, lower extremity amputation, and bleeding were more common in patients with ESRD compared to those with CKD without ESRD. Finally, patients with PAD and renal disease were more likely to be readmitted after revascularization than those without renal disease, with the highest risks for readmission in patients with ESRD. After multivariable adjustment, renal disease remained an independent predictor of in-hospital events and 6-month readmission. These data highlight the poor short-term outcomes of patients with comorbid PAD and renal disease who require lower extremity revascularization.

Adverse risk profiles and postoperative outcomes of patients with PAD and renal disease are consistent with prior data from cohorts with CKD. Renal disease is associated with a high burden of cardiovascular risk factors and medical comorbidities, including heart failure and anemia.^{17, 18} In an analysis of the National Surgical Quality Improvement Program database, Ambur et al. reported an increase in perioperative morbidity in CKD patients following surgical lower extremity revascularization, but this analysis did not include patients undergoing endovascular revascularization and was limited to patients with CLI.¹⁹ Other recent studies examining outcomes of PAD patients with and without CKD who undergo revascularization are small and limited to patients referred for endovascular lower extremity revascularization.^{9–11, 20} Larger studies that report associations between CKD and outcomes in patients with PAD do not select for individuals undergoing lower extremity revascularization.²¹ To our knowledge, the impact of CKD and ESRD on morbidity and mortality in PAD patients undergoing endovascular or surgical lower extremity revascularization has not been previously examined in a large, representative national cohort from the United States.

In the current analysis, CKD and ESRD were associated with a 74% increased risk of perioperative MACE in patients undergoing lower extremity revascularization after adjustment for demographics and clinical covariates. Differences in MACE were driven by significantly greater all-cause in-hospital mortality and stroke in patients with CKD. A greater frequency of myocardial infarctions associated with CKD was also reported. The greater frequency of MACE associated with CKD was observed in PAD patients undergoing both endovascular and surgical lower extremity revascularization.

Higher rates of hospital readmission in patients with PAD and CKD is another concerning finding. Hospital readmission is an important metric increasingly tied to hospital reimbursement, and efforts to reduce hospital readmissions have been promoted by initiatives such as the Hospital Readmissions Reduction Program. In the current analysis, the most common indications for hospital readmission in patients with PAD and recent lower extremity revascularization were cardiovascular disease, endocrine/metabolic issues, and infectious complications. Indications for readmission observed in this analysis are consistent with expected complications of both PAD and renal disease. Patients with PAD frequently have atherosclerotic disease in multiple vascular territories, and are at increased risk for cardiovascular events beyond vascular complications of the lower extremities.^{22, 23} Renal disease is associated with impairments in platelet function that may predispose patients to increased bleeding risks on antithrombotic therapy for PAD. However, renal disease is also paradoxically associated with increased thrombotic events that may lead to early graft failure and/or stent thrombosis.^{24, 25} Complex interactions of bleeding and thrombotic risks in patients with PAD and renal disease warrant further investigation. Metabolic derangements and infectious complications associated with poor renal function are also expected in patients with PAD. Renal disease is associated with an increased risk of infection, due to functional immunosuppression attributed to reduced glomerular filtration rate and albuminuria, as well as due to iatrogenic mechanisms, particularly among patients with ESRD who undergo dialysis.²⁶

As illustrated in the present analysis, renal disease confers substantial risks in patients with PAD who require lower extremity revascularization. These data should inform pre-operative discussions about the risks, benefits, and alternatives to vascular interventions, particularly in PAD patients without urgent indications for lower extremity revascularization. In addition, renewed efforts are necessary to mitigate postoperative risks in this vulnerable cohort. Multidisciplinary collaboration between vascular surgery, cardiology, nephrology, infectious disease, and wound care may enhance the management of patients with PAD to prevent post-procedure complications and reduce hospital readmissions.

Limitations:

There are several limitations to this study. First, this is a retrospective cohort study of a large administrative database. We limited the analysis to patients hospitalized for revascularization of PAD during a 6-month period of a single calendar year, since hospital admissions cannot be tracked across years in the NRD. We identified PAD patients undergoing lower extremity revascularization using ICD-9 diagnosis and procedure codes in a manner consistent with prior reports.^{8, 12} The use of ICD-9 diagnosis codes to identify chronic kidney disease has also been previously validated.¹⁵ Still, clinical characteristics and outcomes ascertained by ICD-9 diagnosis and procedure codes may be subject to misclassification or miscoding. We cannot exclude the possibility of unmeasured confounding and treatment selection bias, particularly since patients with renal disease were more likely to undergo endovascular versus surgical revascularization. Second, the NRD does not include data on the results of clinical or laboratory tests, and estimated glomerular filtration rate, ankle-brachial index, peripheral artery anatomy, and other measures of PAD severity could not be established. Similarly, in-hospital and discharge medications were not recorded. Third, only in-hospital outcomes could be assessed, since the NRD does not include data on out-of-hospital mortality.

Conclusion

Chronic kidney disease and ESRD are common among hospitalized patients undergoing lower extremity revascularization for PAD in the United States. Renal disease was independently associated with in-hospital major adverse events and readmission within 6 months. Additional efforts to improve outcomes of patients with CKD and PAD requiring revascularization are necessary.

Highlights.

• 26.7% of patients undergoing LE revascularization for PAD had renal disease.

• CKD disease confers a 2-fold risk of in-hospital MACE after LE revascularization

• 6-month readmission after revascularization was more common in patients with CKD.

• CKD is associated with outcomes after endovascular and surgical revascularization.