Metal deposition in calcific uremic arteriolopathy

Abstract

Background: Calcific uremic arteriolopathy (CUA) is an often fatal disease that affects patients with end-stage renal disease. Although animal studies support a role for metals in the pathogenesis of CUA, metal accumulation in human tissue has not been previously evaluated.

Objective: We sought to evaluate metal deposition in CUA.

Methods: Twelve histologically proven cases of CUA were identified from our dermatopathology database. Five skin biopsy specimens from patients with chronic kidney disease exposed to gadolinium contrast but without CUA were used as controls. Quantification of metals including iron, aluminum, and gadolinium in the lesional skin was performed using inductively coupled mass spectrometry.

Results: Seven patients had documented exposure to gadolinium-based contrast in the 2 years before CUA. Three of them had concurrent nephrogenic systemic fibrosis. Highly significant quantities of iron (P = .03) and aluminum (P = .0002) were detected in CUA specimens compared with controls. Significant amounts of gadolinium were present in several CUA biopsy specimens.

Limitations: Observational, retrospective study design and small sample size are limitations.

Conclusion: Tissue iron and aluminum content is increased in CUA. A significant amount of gadolinium is also present in some CUA specimens. Based on animal studies that strongly implicate metals in the pathogenesis of CUA, our data suggest that metal deposition should be considered in the pathogenesis of human CUA.

Figure 1. Skin biopsy of a patient with concurrent NSF and calciphylaxis

The low power image shows a biopsy of a patient with concurrent nephrogenic systemic fibrosis characterized by increased activated fibroblasts and collagen in the deep dermis and extending along the interlobular septae (insert A) and calciphylaxis characterized by calcification of the intima of small vessels in the subcutaneous tissue (insert B). Insert A shows increased dermal cellularity, primarily consisting of reactive type fibroblasts. Insert B shows subcutaneous tissue that contains many small vessels with intimal calcification and some with complete occlusion of the lumen. Significant amounts of gadolinium (60 μg/g), iron (1097 μg/g) and aluminum (1988 μg/g) were present in this biopsy.

Figure 2

Schematic description of pathogenic pathways in calciphylaxis.