Vascular calcification in skin and subcutaneous tissue in patients with chronic and end-stage kidney disease

BMC Nephrol. 2020 Jul 16;21(1):279. doi: 10.1186/s12882-020-01928-0.

Abstract

Background: 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. 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.

Methods: We 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).

Results: Forty-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.

Conclusion: This 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.

Keywords: Calcific uraemic arteriolopathy; Chronic kidney disease; End-stage kidney disease; Vascular calcification.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen
  • Adult
  • Aged
  • Alkaline Phosphatase / genetics
  • Arm
  • Case-Control Studies
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / metabolism*
  • Male
  • Middle Aged
  • Neck
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / metabolism
  • Skin / blood supply
  • Skin / metabolism
  • Skin / pathology*
  • Subcutaneous Tissue / blood supply
  • Subcutaneous Tissue / metabolism
  • Subcutaneous Tissue / pathology*
  • Vascular Calcification / etiology
  • Vascular Calcification / genetics
  • Vascular Calcification / metabolism
  • Vascular Calcification / pathology*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human
  • ALPL protein, human
  • Alkaline Phosphatase