Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross-sectional study

Journal of Nephrology https://doi.org/10.1007/s40620-023-01707-8 ORIGINAL ARTICLE Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross‑sectional study Anne Kristine Røndbjerg1,2,3 · Mette Gyldenløve4 · Dorrit Krustrup5 · Marianne Rix2 · Ilse Vejborg6 · Lars Lonn7,11 · Niklas Rye Jørgensen8,11 · Andreas Pasch9,10 · Lone Skov4,11 · Ditte Hansen3,11,12 Received: 12 March 2023 / Accepted: 9 June 2023 © The Author(s) 2023 Abstract Introduction Calcific uremic arteriolopathy is a life-threatening cutaneous condition in patients with chronic kidney disease. Often, clinical diagnosis is accompanied by histopathologic evaluations demonstrating vascular calcium deposits. We aimed to investigate the presence of cutaneous calcifications in non-lesional tissue in patients with chronic kidney disease, and the relation to systemic vascular calcification. Methods We investigated the presence of cutaneous vascular calcifications in non-lesional skin biopsies from patients with current or previous calcific uremic arteriolopathy and patients with different stages of chronic kidney disease without calcific uremic arteriolopathy, and explored their association with vascular calcification in other vascular beds. Systemic vascular calcification was examined by mammography and lumbar X-ray. Results Thirty-nine adults were enrolled (current or previous calcific uremic arteriolopathy, n = 9; end-stage chronic kidney disease, n = 12; chronic kidney disease stage 3b-4, n = 12; healthy controls, n = 6). All calcific uremic arteriolopathy patients had end-stage kidney disease. Cutaneous vascular calcifications were not present in any of the non-lesional skin punch biopsies. Breast arterial calcification was demonstrated in patients with calcific uremic arteriolopathy (75%) and chronic kidney disease (end-stage 67% and stage 3b-4 25%, respectively), but in none of the controls. All chronic kidney disease patients had systemic calcification on lumbar X-ray (median score 21, 22, and 15 in patients with calcific uremic arteriolopathy, end-stage kidney disease and chronic kidney disease stage 3b-4). The serum calcification propensity was significantly different between groups. Discussion Despite a high burden of systemic vascular calcification, cutaneous calcium deposits in non-lesional tissue could not be demonstrated histopathologically in patients with chronic kidney disease (with or without current or previous calcific uremic arteriolopathy). Further studies to determine whether these findings are representative or attributed to other factors are warranted. 7 Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Denmark 8 Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Denmark 9 Calciscon, Biel, Switzerland 10 Department of Nephrology, Copenhagen University Hospital, Herlev, Denmark Department of Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria 11 Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark Department of Clinical Medicine, University of Copenhagen, Herlev, Denmark 12 Department of Nephrology, Herlev and Gentofte Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark * Ditte Hansen 1 Department of Internal Medicine, University Hospital Zealand, Roskilde, Denmark 2 Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Denmark 3 4 5 Department of Pathology, Copenhagen University Hospital, Herlev, Denmark 6 Department of Breast Examinations, Copenhagen University Hospital, Gentofte, Denmark 13 Vol.:(0123456789) Journal of Nephrology Graphical abstract Cutaneous vascular calcificaons in paents with chronic kidney disease and calcific uremic arteriolopathy – a cross-seconal study AK Rønbjerg, M Gyldenløve, D Krustrup, M Rix, I Vejborg, L Lonn, NR Jørgensen, A Pasch, L Skov, D Hansen Background Results Calcific uremic arteriolopathy (CUA) is a rare, life-threatening condion, which mainly presents in paents with chronic kidney disease (CKD). The aim of the present study was to invesgate the presence of cutaneous calcificaons in non-lesional skin in paents with different stages of CKD including CUA and the relaon to systemic vascular calcificaon. Cutaneous vascular calcificaons in non-lesional skin could not be demonstrated. Breast Arterial Calcificaon (BAC) Lumbar X-ray Abdominal Aorc Calcificaon (AAC) Biochemial markers of vascular calcificaon T50 T50, Fetuin A and dp-ucMGP Journal of NEPHROLOGY official journal of the Italian Society of Nephrology CKD3b-4 Control Kauppila score ESKD w/o CUA 12 6 0 ESKD w CUA Fetuin A ESKD w ESKD w/o CKD3b-4 Control CUA CUA ESKD w/o CUA CKD3b-4 Control dp-ucMGP pmol/L Current or previous CUA, n=9 End-stage CKD, n=12 CKD stage 3b-4, n=12 Healthy controls, n=6 Mammography ESKD w CUA 24 18 g/L N = 39 pa ents Percentage of Paents Cross-seconal Non-lesional skin punch biopsy 100 80 60 40 20 0 Minutes Method Methods Abdominal aor c calcifica on Breast arterial calcifica ons ESKD w ESKD w/o CKD3b-4 Control CUA CUA ESKD w ESKD w/o CKD3b-4 Control CUA CUA Conclusion Vascular calcificaons could not be demonstrated in non-lesional skin in paents with CKD, parcularly CUA, despite the presence of systemic vascular calcificaon, measured by BAC and AAC, and disturbed levels of biomarkers for vascular calcificaon. The findings support that skin punch biopsies cannot be used in risk straficaon or screening for CUA. Keywords Calcific uremic arteriolopathy · Chronic kidney disease · Calcifications · Calcification propensity Introduction Methods Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare, life-threatening condition, which mainly occurs in patients with chronic kidney disease (CKD). Initially, patients typically present with rather unspecific skin manifestations, which rapidly progress into multiple, intensely painful, ischemic lesions. Sepsis is the most common cause of death. The pathogenesis of CUA is poorly understood but likely results from an imbalance between calcification promoters and inhibitors [1]. Clinically suspected CUA is frequently supported by histopathologic evaluations. The diagnostic value of biopsies is questioned, as the histopathological changes have also been demonstrated in CKD patients without CUA [2–4]. In addition, skin biopsy is even suggested to propagate or complicate the disease [5]. Outside the setting of CUA, cutaneous calcifications in non-lesional tissue are rarely investigated in patients with CKD. The primary aim of this study was to describe the presence of small-vessel cutaneous calcifications in nonlesional tissue in patients with different stages of CKD, including patients with current or previous CUA. The relation to systemic vascular calcification was examined. Study protocol an (...truncated)