Pathological Analysis of Medial and Intimal Calcification in Lower Extremity Artery Disease: Impact of Hemodialysis

Background: The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated.

Objectives: The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification.

Methods: Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification.

Results: The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group (P < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; P = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque (P = 0.02). The prevalence of severe bone formation was more common in the HD patients (P = 0.01).

Conclusions: Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.