Heparin-Mediated Extracorporeal Low-Density Lipoprotein Precipitation Apheresis for Treating Peripheral Arterial Disease in Patients with Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), have a high prevalence of cardiovascular disease and peripheral arterial disease (PAD). Medical treatment is mainly based on risk factor management, and the surgical approach remains the gold standard treatment in specific conditions. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis is effective in reducing circulating lipoprotein, fibrinogen, inflammatory mediators and procoagulant factors, thereby reducing cardiovascular risk in patients with familial hypercholesterolemia and hypertriglyceridemia. These activities may be effective in reducing symptoms and ischemic vascular lesions even in patients with severe PAD. We reported the application of a treatment protocol with H.E.L.P. apheresis in an ESRD patient with severe PAD without clinical improvement after severe revascularization who was not suitable for further surgical approaches, despite normal LDL cholesterol and lipoprotein (a). The H.E.L.P. protocol was characterized by an intensive first phase with weekly treatments followed by a single session every 10-15 days for 6 months of treatment. The overall clinical condition, foot lesions and walking distance improved significantly after the first 2 months of treatment, and foot amputation was avoided. Here, we review the main pathogenetic mechanisms through which LDL apheresis improves microcirculation and clinical outcomes. Its wider application may represent an optimal therapeutic option for patients unresponsive to standard treatment.

Keywords: chronic kidney disease; heparin-mediated extracorporeal low-density lipoprotein precipitation; peripheral arterial disease.

Figure 1

Angio-CT scan of the vascular axis in the case patient. (A) abdominal aorta with severe calcification and thrombotic plaques; (B) common iliac arteries with diffuse concentric parietal thrombotic apposition; (C) femoral arteries with diffuse parietal fibrocalcific apposition with irregular lumen; (D) femoral arteries with reduced lumen, particularly on the left side. (E) On the right side, pervious and diffusely atheromatic femoral popliteal axis. On the left, diffuse thrombotic apposition of the superficial femoral artery with presence of stenting to the popliteal axis. (F–H) Posterior tibial and interosseous arteries appear threadlike and tenuously opacified, especially in distal sections.

Figure 2

Treatment protocol. Legend: H.E.L.P, heparin-mediated extracorporeal LDL precipitation.

Figure 3

Ischemic foot lesions before treatment initiation (a), after 2 months (b) and after 6 months of treatment with H.E.L.P. apheresis (c).

Figure 3

Ischemic foot lesions before treatment initiation (a), after 2 months (b) and after 6 months of treatment with H.E.L.P. apheresis (c).

Figure 4

Main therapeutic effects of LDL apheresis. Legend: ICAM-1, intercellular adhesion molecule-1; LDL, low-density lipoprotein; NO, nitric oxide; VCAM-1, vascular adhesion molecule-1.