1. Low Levels of High-Density Lipoproteins are associated with Acute Kidney Injury following Open/ Endovascular Revascularization for Chronic Limb Ischemia
Nader D. Nader, MD, PhD, Pradeep Arora, MBBS, Hasan H. Dosluoglu, MD
VA Western New York Healthcare System
Abstract
Data Source
Statistical Modeling
TABLE ONE
High HDL
(N=296)
Low HDL
(N=459)
P value
Age (years)
68.9±11.2
68.1±10.5 NS
BMI (kg/m2)
26.8 ±3.6
26.9±4.0
Smoking
92.6%
93.4%
0.46 DM
37.8%
53.2%
0.001
HTN
70.3%
76.9%
0.15
CAD
53.4%
59.3%
0.60
CVD
16.9%
18.3%
0.58
COPD
30.4%
23.7%
0.04
CKD
14.2%
22.4%
0.004
B-blocker use
58.6%
ACEI/ARB
51.0%
55.2%
0.25
Statin Use
51.8%
63.2%
Aspirin use
75.3%
78.6%
0.28
AKI
5.7%
13.3%
0.0001
The study population included all patients who presented with disabling claudication, ischemic rest pain, or tissue loss and underwent revascularization using open surgical, endovascular or hybrid revascularization of the lower extremities between January 1, 2001 and December 31, The VA Western New York Healthcare System has maintained a prospective database of patients undergoing revascularization procedure for peripheral arterial disease of lower extremities since These data are in part reported to the National Surgical Quality Improvement Program. The institutional review board at the VA Western New York Healthcare System for quality improvement research has evaluated and approved the use of this database.
Objective: To examine the association of high-density lipoproteins (HDL) and
perioperative acute kidney injury (AKI) in patients undergoing revascularization of lower extremities.
Study Design: Cohort Study
Subjects: 684 patients who underwent vascular intervention/surgery for
symptomatic chronic limb ischemia at the between 01/ /2009.
Main Outcome Measures: Acute kidney injury as defined by Acute Kidney Injury Network (AKIN), mortality
Results: 684 patients (32% open, 68% endovascular/hybrid) were included in final analysis. 85 patients developed post-operative AKI. The patients who developed AKI were more likely to have diabetes mellitus, HDL <40, LDL/HDL >4.9, and preexisting CKD. Multivariate analysis using logistic as well as propensity score revealed that low HDL level (HR=2.4 [ ]) and underlying CKD were independent factors associated with AKI (P<0.001).
Conclusions: AKI is common (12.4%) following revascularization for chronic limb ischemia. A low concentration of HDL is associated with increased odds of AKI after revascularization of the lower extremities. Strategies for increasing the HDL level in patients with high risk of postoperative AKI should be investigated.
Patients were divided into those with high HDL (≥40 mg/dl) and low HDL group (<40 mg/dl). The comparison was performed using Wilcoxon rank sum test and the comparison of proportions was done using the Chi-square test. Logistic regression models were used to determine the effect of low HDL on development of AKI. The preoperative variables which showed a predictive trend with a p value of <0.1 were selected for multivariate analysis. Multivariate analysis was also performed, adjusted for age, ASA status, LDL levels, hypertension, preoperative use of statins, and ACE inhibitor (variables known to be related to post-operative AKI). Multivariate logistic regression was also done following data matching to eliminate other perplexing factors. Tests were 2-tailed, and values of P <0.05 were considered statistically significant. Propensity scores were estimated using a logistic model including the following variables; age, ASA scores, hypertension, coronary artery disease, congestive heart failure, renal insufficiency, diabetes, current smoker, preoperative creatinine levels and use of ACE inhibitors. Statistical analyses were performed with NCSS-2007.
Patient Population
The laboratory information and follow up visitations were extracted from the VISTA-based Computerized Patient Record (CPRS) and entered into the Excel database. Patients were excluded from the study if they had prior vascular procedures within the past 30 days, a primary amputation of a lower extremity (below or above knee amputations), or if they had end-stage renal diseases. They were also excluded if there was no baseline creatinine level or lipid profile measured within 30 days prior to the date of procedure. When both endovascular and open surgery were listed as the approach while intravenous contrast material was used during the procedure, the surgical plan was listed as endovascular approach for analysis. A total of 1056 patients were identified initially. The following exclusions were made for patients with missing age and/or gender information: (6 patients, 0.5% and gender 7 patients, 0.52%). Seven hundred and sixty patients were included in final analysis after excluding patients who had amputation as primary surgery or were at the end-stage renal disease (ESRD) prior to procedure.
Data collected for each patient included age at the time of surgery, gender, race (Caucasian or other), body mass index, current smoker (patient smokes or has quitted for less than 3 months), coronary artery disease (CAD), hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), cerebrovascular accident (CVA), preoperative use of niacin, statins, angiotensin converting enzyme inhibitors/angiotensin receptor blocker (ACEI/ARB), beta blockers, and preoperative serum creatinine. Polynomial categorical variables included Rutherford score, American Society of Anesthesiologists Physical Status and Functional Status of the patient at the time the primary surgical procedure. Missing data variables were treated to limit the introduction of bias by their exclusion. Outcome data did include death, and estimated glomerular filtration rate (eGFR).
AKI was defined using the Acute Kidney Network (AKIN) criteria: increase in serum creatinine of ≥ 0.3mg/dl (25 μmol/l) or an increase of % from baseline.
Results
Figure One Figure Two
754 patients who underwent vascular intervention/surgery. The mean age of patients was 68.6±10.6 years. The mean BMI was 29.3± % had diabetes, 74.1% had hypertension, 56.9% had CAD and 26.4% with COPD % of patients had underlying CKD. The distribution of demographic variables, co-morbidities, is shown in (Table One). 78 patients (10.3%) developed AKI. Patients who developed AKI were more likely to have DM and were more likely to be on ACEI. There was no significant difference between age, race, BMI, and the presence of HTN, CVA, COPD or CAD. There were more patients with critical limb ischemia in the AKI group (36.7%) when compared to patients who did not develop AKI (16.3%), postoperatively (p<0.01). We also analyzed the incidence of AKI by LDL and HDL levels. Patients who had LDL <100, low HDL was not associated with AKI (15% vs 12% P value 0.39). However among patients with preoperative LDL >100, low HDL was associated with increased odds of AKI (21% vs 3.5% p = <0.001)
Multivariate logistic regression model revealed that low HDL was associated with increased risk of AKI, postoperatively. Adding multiple variables to the model all revealed HDL<40 as a significant independent risk factor for post-operative AKI (Table 3). Analyses were also done for adjusting LDL level and statin use, low HDL was associated with increased odds of AKI (Figure One). Propensity score analyses revealed that low HDL level prior to vascular procedure /surgery was associated with 40% increased odds of AKI ( ). Although there was an increase in mortality associated with perioperative AKI (HR=1.42[ ], high HDL concentration had no clear survival advantage in our patient population over a period of 7 years follow up (Figure Two).
Introduction
Peripheral vascular procedures are associated with higher risk of acute kidney injury (AKI) and consequently higher rate of chronic kidney disease (CKD) and therefore more frequent morbidity on a long term follow up. Prior to the evaluation done in this study, there is no data available on the development of AKI in the population. The HDLs are a family of particles of differing size and composition. High-density lipoproteins (HDL) have been shown to reduce organ injury and mortality in animal models of shock via modulation of the expression of adhesion molecules and pro-inflammatory enzymes. Renal inflammation plays an important role in the development of ischemia/reperfusion (I/R) injury of the kidney. Based on above observations, it is postulated that HDL concentration may have a protective effect on ischemia reperfusion injury in humans.
Conclusion
Animal model studies done during the last decade have demonstrated that there are multiple mechanisms involved in the renoprotective effects of HDL. In ischemia reperfusion model, HDL not only reduces tissue inflammation after initial insult but also result in robust recovery of renal function.
To the best of our knowledge, this is the first report showing the actual prevalence of AKI in prospectively collected data in this subgroup of patients. There were several other factors associated with AKI; however we were interested in studying the association of HDL and AKI specifically. The incidence of AKI using AKIN definition after vascular procedure was 10%. Multivariate logistic model and propensity score analyses revealed that low HDL was associated with increased risk of AKI.
Hypothesis
HDL levels below 40 mg/dL are good predictors of acute post-revascularization kidney injury in patients with peripheral arterial diseases.