Abstract
BackgroundVascular calcification (VC) is well described in large- and medium-sized vessels in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on dialysis. Medial calcification is particularly prevalent in this population and contributes to arterial stiffness and increased cardiovascular mortality and morbidity. Apart from in the setting of calciphylaxis, few studies have assessed skin and subcutaneous calcification and associations with abnormalities of bone and mineral metabolism in patients with CKD.MethodsWe performed a single-centre observational study to evaluate incisional skin tissue samples from three anatomical sites in patients with different stages of CKD undergoing elective surgery. We compared these samples to skin samples of a control cohort without CKD. Staining for calcification was performed with von Kossa method. A subgroup of skin samples were assessed by RT-PCR for upregulation of pro-calcific gene transcripts for tissue non-specific alkaline phosphatase (TNAP) and Runt-related transcription factor 2 (RUNX2).ResultsForty-five patients were evaluated, 34 with CKD (including ESKD) and 11 control patients. VC was identified in 15 skin samples (13 CKD/ESKD and 2 controls). VC was present in the dermal and subcutaneous tissues of the neck, abdomen and arm samples. Two different histological types of VC were identified: speckled medial calcification and internal elastic lamina calcification. Presence of perieccrine calcification was identified in 14 samples, 10 with concurrent VC. There were no significant differences in serum parathyroid hormone, phosphate or calcium in patients with or without VC. Expression of TNAP or RUNX2 was not increased in samples from patients with ESKD or those with histological evidence of calcification.ConclusionThis study reports the novel finding of dermal and subcutaneous calcification in multiple anatomical locations in 38% of patients with advanced CKD/ESKD undergoing elective surgery but free from calciphylaxis.
Highlights
Vascular calcification (VC) is well described in large- and medium-sized vessels in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on dialysis
The presence of VC of small vessels in the skin and subcutaneous tissue has only been systemically described in ESKD patients with calciphylaxis [8], recent studies suggest even this may not be a specific finding and VC can be present in patients with peripheral vascular disease without the presence of calciphylaxis [7]
[12] To date, there is little information about the prevalence of calcification in skin and subcutaneous tissue in patients with advanced CKD and ESKD outside the setting of calciphylaxis, and if present, whether it is related to disordered bone and mineral metabolism
Summary
Vascular calcification (VC) is well described in large- and medium-sized vessels in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on dialysis. Vascular calcification (VC) is prevalent and well described in large- and medium-sized vessels of patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on dialysis [1, 2]. Medial arterial calcification has been identified in multiple anatomical locations in patients with ESKD, including normal breast tissue from mastectomy samples [6], as well as subcutaneous tissue of lower limb amputations [7] In both locations, VC has been identified in vessels in the presence of other patient risk factors for calcification, including active malignancy or peripheral vascular disease. Calciphylaxis is a rare condition and only occurs in a very small minority of patients with ESKD with approximately 3.5 cases per 1000 patient years in those receiving chronic haemodialysis therapy [12] To date, there is little information about the prevalence of calcification in skin and subcutaneous tissue in patients with advanced CKD and ESKD outside the setting of calciphylaxis, and if present, whether it is related to disordered bone and mineral metabolism
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