Combined predictive value of pre-procedural protein-energy wasting and inflammation status for amputation and/or mortality after lower extremity revascularization in patients on hemodialysis

Abstract

Abstract Background Although lower extremity revascularization has been commonly performed in chronic hemodialysis (HD) patients with peripheral artery disease (PAD), poorer prognosis after revascularization still remains major problems. Recently, protein-energy wasting (PEW) or malnutrition have been considered to be strongly associated with chronic inflammation and advanced atherosclerosis in HD patients. We investigated the association of geriatric nutritional risk index (GNRI) as a surrogate marker of the PEW, C-reactive protein (CRP) and their joint role with prediction of amputation and/or mortality after lower extremity revascularization in HD patients. Method We enrolled a total of 800 HD patients (age 67±10 years, diabetes 63.3% and critical limb ischemia 52.9%) who successfully underwent lower extremity revascularization [535 with endovascular therapy (EVT) and 265 with bypass surgery]. Patients were divided into tertiles according to pre-procedural GNRI levels; tertile 1 (T1): <88.1, T2: 88.1-96.7and T3: >96.7, and CRP levels; T1: <2.0mg/l, T2: 2.0-12.6mg/l and T3: >12.6mg/l, respectively. Primary outcome was amputation-free survival (AFS). They were followed up for up to 8 years. Results During follow-up period (median: 43 months), 56 (7.0%) patients needed major amputation and 183 (22.9%) patients died. Kaplan-Meier analysis shows that the AFS rates for 8 years were 47.0%, 56.9% and 69.5% in T1, T2 and T3 of GNRI, and were 65.8%, 58.7% and 33.2% in T1, T2 and T3 of CRP, respectively (p<0.0001 in both). After adjustment for male, age, previous coronary artery disease, procedure (EVT vs. bypass surgery), below-knee artery disease and ulcer/gangrene as covariates with p<0.05 by univariate analysis, declined GNRI [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.57-3.07, p<0.0001 for T1 vs. T3] and elevated CRP (HR 1.78, 95%CI 1.24-2.59, p=0.0016 for T3 vs. T1) were identified as independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk of amputation and/or mortality was 3.77-fold higher (95%CI 1.97-7.69, p<0.0001) in the group with T1 of GNRI and T3 of CRP than in that with T3 of GNRI and T1 of CRP (Figure). Addition of GNRI and CRP in a predicting model with established risk factors improved C-statistics (0.661 to 0.716, p=0.0021) greater than that of each alone. Conclusion Among HD patients undergoing lower extremity revascularization for PAD, those with pre-procedural declined GNRI and elevated CRP frequently experienced amputation and/or mortality, furthermore, combination of both variables could more accurately stratify the risk of amputation and/or mortality.