Abstract 136: Chronic Kidney Disease Aggravates Ischemic Leg Myopathy In Patients With Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) often present with comorbid risk factors that accelerate disease evolution and worsen clinical outcomes. Notably, PAD patients with chronic kidney disease (CKD) have greater risk for major adverse limb events and mortality. The objective of this study was to determine the impact of CKD on skeletal muscle strength and mitochondrial health in patients with and without PAD. Methods: We performed a cross-sectional analysis of skeletal muscle strength and mitochondrial health in four groups of patients (58 males and 21 females): PAD only (Toe brachial index, TBI<0.5 and eGFR>60 mL/min), CKD only (TBI>0.75 and eGFR:15-45 mL/min), PAD with CKD (TBI<0.5 and eGFR:15-45 mL/min), and adult controls without PAD and CKD (TBI>0.75 and eGFR>60 mL/min). Results: Plantar flexor muscle strength was lowest in PAD patients with CKD, which had a significant difference from adult controls ( P <0.01), a trending difference ( P =0.08) from PAD patients without CKD. Myofiber cross-sectional area was 20-25% larger in PAD only patients and adult controls compared to CKD and PAD+CKD groups without significance. Analysis of mitochondrial oxidative phosphorylation (OXPHOS) revealed that both CKD and PAD with CKD groups had significant reduction (30~40%) in mitochondrial bioenergetic function at various levels of energy demand mimicking from resting skeletal muscle to maximal contraction compared with adult controls and PAD without CKD group (P<0.05). Similarly, OXPHOS conductance was significantly reduced in the PAD with CKD group compared with both adult controls and PAD patients without CKD ( P <0.01). Surprisingly, patients with CKD only had lower OXPHOS conductance compared to adult controls ( P =0.05) and patients with PAD only ( P =0.02). Interestingly, PAD patients without CKD had no difference in mitochondrial function compared with adult controls ( P =0.98). Conclusion: The results suggest that CKD plays a critical role in exacerbating skeletal myopathy evidenced by muscle weakness and mitochondrial dysfunction in patients with PAD. These findings suggest that mitochondrial dysfunction may be a primary site of convergence of these two diseases. Funding: NIH grant R01HL149704 and AHA grant POST903198.