Skip to main content

Advertisement

SpringerLink
Log in

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion

  • Case Report
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

References

  1. McCarthy JT, El-Azhary RA, Patzelt MT, Weaver AL, Albright RC, Bridges AD, Claus PL, Davis MD, Dillon JJ, El-Zoghby ZM, Hickson LJ, Kumar R, McBane RD, McCarthy-Fruin KA, McEvoy MT, Pittelkow MR, Wetter DA, Williams AW (2016) Survival, risk factors, and effect of treatment in 101 patients with calciphylaxis. Mayo Clin Proc 91(10):1384–1394. https://doi.org/10.1016/j.mayocp.2016.06.025

    Article  PubMed  Google Scholar 

  2. Nigwekar SU, Zhao S, Wenger J, Hymes JL, Maddux FW, Thadhani RI, Chan KE (2016) A nationally representative study of calcific uremic arteriolopathy risk factors. J Am Soc Nephrol 27(11):3421–3429

    Article  CAS  Google Scholar 

  3. Hayashi M (2013) Calciphylaxis: diagnosis and clinical features. Clin Exp Nephrol 17(4):498–503. https://doi.org/10.1007/s10157-013-0782-z

    Article  CAS  PubMed  Google Scholar 

  4. Brandenburg VM, Kramann R, Rothe H, Kaesler N, Korbiel J, Specht P, Schmitz S, Krüger T, Floege J, Ketteler M (2017) Calcific uraemic arteriolopathy (calciphylaxis): data from a large nationwide registry. Nephrol Dial Transplant 32(1):126–132. https://doi.org/10.1093/ndt/gfv438

    Article  CAS  PubMed  Google Scholar 

  5. Oliveira TM, Frazão JM (2015) Calciphylaxis: from the disease to the diseased. J Nephrol. 28(5):531–540. https://doi.org/10.1007/s40620-015-0192-2

    Article  CAS  PubMed  Google Scholar 

  6. Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, Bovi M, Jahnen-Dechent W, Knüchel R, Floege J, Schneider RK (2013) Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant 28(4):856–868. https://doi.org/10.1093/ndt/gfs466

    Article  CAS  PubMed  Google Scholar 

  7. Nigwekar SU, Kroshinsky D, Nazarian RM, Goverman J, Malhotra R, Jackson VA, Kamdar MM, Steele DJ, Thadhani RI (2015) Calciphylaxis: risk factors, diagnosis, and treatment. Am J Kidney Dis 66(1):133–146. https://doi.org/10.1053/j.ajkd.2015.01.034

    Article  PubMed  PubMed Central  Google Scholar 

  8. Brandenburg VM, Cozzolino M, Mazzaferro S (2014) Calcific uremic arteriolopathy: a call for action. Semin Nephrol 34(6):641–647. https://doi.org/10.1016/j.semnephrol.2014.09.007

    Article  PubMed  Google Scholar 

  9. Ellis CL, O’Neill WC (2018) Questionable specificity of histologic findings in calcific uremic arteriolopathy. Kidney Int 94(2):390–395. https://doi.org/10.1016/j.kint.2018.03.016

    Article  PubMed  Google Scholar 

  10. Williams EA, Moy AP, Cipriani NA, Nigwekar SU, Nazarian RM (2019) Factors associated with false-negative pathologic diagnosis of calciphylaxis. J Cutan Pathol 46(1):16–25. https://doi.org/10.1111/cup.13364

    Article  PubMed  Google Scholar 

  11. Nigwekar SU, Thadhani R, Brandenburg VM (2018) Calciphylaxis. N Engl J Med 378:1704–1714. https://doi.org/10.1056/nejmra1505292

    Article  CAS  PubMed  Google Scholar 

  12. Brandenburg VM, Evenepoel P, Floege J, Goldsmith D, Kramann R, Massy Z, Mazzaferro S, Schurgers LJ, Sinha S, Torregrosa V, Urena-Torres P, Vervloet M, Cozzolino M, Era-Edta Working Group on CKD-MBD Eucalnet (2016) Lack of evidence does not justify neglect: how can we address unmet medical needs in calciphylaxis? Nephrol Dial Transplant 31:1211–1219. https://doi.org/10.1093/ndt/gfw025

    Article  PubMed  Google Scholar 

  13. Udomkarnjananun S, Kongnatthasate K, Praditpornsilpa K, Eiam-Ong S, Jaber BL, Susantitaphong P (2019) Treatment of calciphylaxis in CKD: a systematic review and meta-analysis. Kidney Int Rep 4(2):231–244. https://doi.org/10.1016/j.ekir.2018.10.002

    Article  PubMed  Google Scholar 

  14. Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr (2013) Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol 8(7):1162–1170. https://doi.org/10.2215/cjn.09880912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brandenburg V, Sinha S, Torregrosa JV, Garg R, Miller S, Canals AZ, Bahr D, Joubert PH, Salcedo C, Carroll KJ, Gold A, Perelló J (2019) Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis. J Nephrol. 32(5):811–821. https://doi.org/10.1007/s40620-019-00631-0

    Article  CAS  PubMed  Google Scholar 

  16. Pasquali M, De Martini N, Mazzaferro S (2019) Calciphylaxis: a conundrum for patients and nephrologists? J Nephrol. 32(5):677–680. https://doi.org/10.1007/s40620-019-00639-6

    Article  PubMed  Google Scholar 

  17. Brandenburg V, Adragao T, van Dam B, Evenepoel P, Frazão JM, Ketteler M, Mazzaferro S, Urena Torres P, Ramos R, Torregrosa JV, Cozzolino M (2015) Blueprint for a European calciphylaxis registry initiative: the European Calciphylaxis Network (EuCalNet). Clin Kidney J 8(5):567–571. https://doi.org/10.1093/ckj/sfv056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dialysis Unit at ICOT Hospital, Latina, Italy

    Silverio Rotondi, Lida Tartaglione, Maria Luisa Muci & Sandro Mazzaferro

  2. Department of Translational and Precision Medicine, Nephrology Unit at Policlinico Umberto I Hospital, Sapienza University of Rome, Viale del Policlinico 153, 00161, Rome, Italy

    Natalia De Martini & Sandro Mazzaferro

  3. Department of Medical-Surgical Sciences and Biotechnologies Pathology Unit, ICOT Hospital, Latina, Italy

    Vincenzo Petrozza, Natale Porta & Martina Leopizzi

  4. Department of Medical-Surgical Sciences and Biotechnologies, “Daniele Innocenzi” Dermatological Unit, Sapienza, University of Rome, Rome, Italy

    Ilaria Proietti, Concetta Potenza & Nevena Skroza

Authors
  1. Silverio Rotondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia De Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lida Tartaglione
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Luisa Muci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vincenzo Petrozza
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natale Porta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martina Leopizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ilaria Proietti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Concetta Potenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nevena Skroza
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sandro Mazzaferro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandro Mazzaferro.

Ethics declarations

Conflict of interest

There are no conflicts of interest for the current study.

Ethical standards

All the procedures involving humans in this study were in agreement with common and standard clinical practice and in accordance with institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rotondi, S., De Martini, N., Tartaglione, L. et al. On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion. J Nephrol 33, 859–865 (2020). https://doi.org/10.1007/s40620-019-00678-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-019-00678-z

Search

Navigation