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Published on: June 2, 2022
Vascular calcification in skin and subcutaneous tissue in patients with chronic and end-stage kidney disease
Irene Ruderman1,2, Tim D Hewitson3,4, Edward R Smith3,4
1Department of Nephrology, The Royal Melbourne Hospital, 300 Grattan St, Parkville, Victoria, 3050, Australia. irene_ruderman@hotmail.com.
Insights
Vascular calcification (VC) affects skin and subcutaneous tissues in 38% of advanced chronic kidney disease (CKD) patients. This study identified VC in multiple body sites, highlighting a previously under-recognized complication in CKD patients not experiencing calciphylaxis.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Dermatology
Background:
- Vascular calcification (VC) is common in large vessels of chronic kidney disease (CKD) patients, particularly end-stage kidney disease (ESKD) on dialysis.
- Medial calcification in CKD contributes to arterial stiffness, increasing cardiovascular risks.
- Skin and subcutaneous calcification in CKD, outside of calciphylaxis, is understudied.
Purpose of the Study:
- To investigate the prevalence and characteristics of dermal and subcutaneous VC in CKD patients.
- To compare skin calcification in CKD patients with a control cohort.
- To explore associations with bone and mineral metabolism and specific gene expression.
Main Methods:
- An observational study evaluated incisional skin tissue samples from three anatomical sites in CKD patients and controls.
- Von Kossa staining assessed calcification, and RT-PCR analyzed gene expression (TNAP, RUNX2) in a subset of samples.
- Patients with varying stages of CKD, including ESKD, were included.
Main Results:
- Vascular calcification (VC) was found in 15 of 45 samples (33%), including 13 from 34 CKD/ESKD patients and 2 from 11 controls.
- VC occurred in dermal and subcutaneous tissues across neck, abdomen, and arm samples, with two histological types identified.
- No significant differences in serum parathyroid hormone, phosphate, or calcium were observed between patients with or without VC; TNAP or RUNX2 expression was not elevated.
Conclusions:
- Dermal and subcutaneous calcification is a novel finding in 38% of advanced CKD/ESKD patients undergoing surgery, independent of calciphylaxis.
- VC was identified in multiple anatomical locations in the skin and subcutaneous tissue.
- The study did not find correlations between VC and standard bone/mineral markers or specific gene upregulation in this cohort.
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.
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