Clinical management of peripheral arterial disease in chronic kidney disease—a comprehensive review from the European Renal Association CKD-MBD Working Group

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Abstract
Peripheral artery disease (PAD) is a common and serious complication in people with chronic kidney disease (CKD) and end-stage kidney disease, occurring four to six times more frequently than in the general population. PAD is characterized by atherosclerotic narrowing or occlusion of peripheral arteries, leads to lower limb ischaemia, and is associated with increased morbidity and mortality. People with CKD and PAD are at higher risk for cardiovascular events and presence of chronic limb-threatening ischaemia further doubles mortality risk in this population. The pathophysiology of PAD in CKD is multifactorial, involving endothelial dysfunction, inflammation, oxidative stress and disordered mineral metabolism; these are key CKD features that exacerbate vascular disease. Traditional risk factors, such as diabetes, hypertension, dyslipidaemia and smoking, also contribute to the development of PAD. Mineral imbalances and metabolic disturbances, seen in CKD-related mineral bone disorders (MBD), including vitamin D deficiency, are an emerging interest area in the development of PAD. Diagnosing PAD in CKD is challenging due to symptom overlap; non-invasive and inexpensive diagnostic tools such as ankle brachial index and toe brachial index offer potential for routine screening. Management of PAD is largely based on guidelines for the general population overlooking the unique differences in CKD patients. A multifaceted approach is fundamental (including lifestyle modifications, pharmacotherapy and, in some cases, revascularization procedures). This comprehensive review (i) outlines the epidemiology, aetiology and pathophysiology of PAD in CKD, (ii) discusses the role of CKD-MBD in PAD and (iii) highlights ongoing studies and the future therapeutic landscape.

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