Background: Calciphylaxis, which mostly affects individuals with end stage kidney disease (ESKD), is also known as calcific uremic arteriolopathy (CUA). It is a rare and fatal disease that manifests with calcification and thrombosis of microvessels, ischemia, and necrosis in skin tissues(ORPHA:280062). Histopathological features of extracutaneous tissues of CUA patients undergoing human amnion derived mesenchymal stem cell (hAMSC) treatment remain unknown. Methods: A female CUA patient, treated with hAMSCs for 20 months, passed away due to stroke. Histopathological features of her extracutaneous tissues were compared with those of ESKD patients (n = 7). Raman spectroscopy was applied to identify the composition of calcifications. The distribution of hAMSCs, derived from the amnion of a male fetus, in tissues of the CUA patient was determined by detecting the Y chromosome using reverse-transcription polymerase chain reaction. Results: Microvessel lesions were more prevalent in the extracutaneous tissues of the CUA patient than in those of ESKD patients, although the regenerated skin showed normal histological characteristics. The CUA patient exhibited calcifications of microvessel media, including the microvessels in the lungs, kidneys, spleen, pancreas, and uterus. Her mitral valve and kidney displayed severe calcification, identified as calcium phosphate with some calcium carbonate. hAMSCs were not detected in the tissues of the CUA patient. Conclusion: Under the treatment strategy with hAMSCs, based on the effects of skin regeneration, microvascular lesions in the extracutaneous tissues of the CUA patient were more severe than those in ESKD patients. CUA should be considered a systemic disease when identifying treatment targets.

The authors have declared no competing interest.

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The National Natural Science Foundation of China (81270408, 81570666, 81730041, and 81671447), the International Society of Nephrology (ISN) Clinical Research Program (18-01-0247), Construction Program of Jiangsu Provincial Clinical Research Center Support System (BL2014084), Jiangsu Province Key Medical Personnel Project (ZDRCA2016002), CKD Anemia Research Foundation from China International Medical Foundation (Z-2017-24-2037), Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), the National Key Research and Development Program of China (2017YFC1001303), the Program of Jiangsu Province Clinical Medical Center (YXZXB2016001, BL2012009), the State Key Laboratory of Reproductive Medicine Program (SKLRM-GC201803), and the Program of Jiangsu Commission of Health (H201605), Jiangsu Province Hospital (the First Affiliated Hospital with Nanjing Medical University) Clinical Capacity Enhancement Project (JSPH-MA-2023-7), Jiangsu Provincial Medical Key Discipline(Laboratory) Cultivation Unit(JSDW202206). All authors declared no competing interests. The study was supported by the ISN Mentorship Program and the authors thank Professor Marcello Tonelli (University of Calgary, Canada) for his helpful comments on the draft of the manuscript. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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