Overlapping Diabetes- and CKD-Driven Vascular Phenotypes of Peripheral Artery Disease: A Limb-First Framework for Chronic Limb-Threatening Ischemia

Despite 90% procedural success, one-year amputation after peripheral artery disease (PAD) revascularization exceeds 20%.Current management treats PAD as uniform atherosclerosis, but distinct biological phenotypes determine outcomes.Diabetes causes inflammatory intimal occlusion with microangiopathy; chronic kidney disease produces medial calcification creating rigid arteries despite patent lumens.These mechanisms coexist in 35-50% of chronic limb-threatening ischemia patients.Lesion-centric approaches fail because angiographic patency does not ensure tissue healing when vascular biology remains pathologic.We propose phenotype-guided management aligning revascularization, diagnostics, and metabolic therapy with underlying pathophysiology to explain why technical success still fails to prevent amputation.