Peripheral artery disease in chronic kidney disease: an underestimated comorbidity

Chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 or the presence of clinical, imaging, or histopathological features of kidney injury over a 3-month period, has been linked to several comorbidities including cardiovascular diseases, such as myocardial infarction, cerebrovascular diseases, renal artery stenosis and peripheral artery disease. A pro-inflammatory and pro-fibrotic state, together with the accumulation of uremic toxins and impaired calcium-phosphorus homeostasis leading to mineral and bone disorders, appear to constitute the underlying pathophysiology of peripheral artery disease in CKD patients. Despite such association and the deleterious effects of peripheral artery disease, the association between CKD and peripheral artery disease is generally underestimated in clinical practice, with physicians being less likely to initiate pharmacotherapy or offer interventional treatments to patients with CKD. Many therapeutic options, including lifestyle modifications, methods for cardiovascular risk reduction such as anti-platelet or lipid-lowering drugs, targeted pharmacotherapies, and endovascular or surgical interventions are available for the management of peripheral artery disease. However, the diagnostic and/or therapeutic process in CKD patients is not as straightforward as it is in the general population, with misleading outcomes and higher treatment-related complications. Aim of this narrative review was to discuss the epidemiology, risk factors, underlying pathophysiology, and diagnostic and therapeutic approaches toward peripheral artery disease in CKD patients.