Calciphylaxis has high mortality. Vitamin K deﬁciency is common in haemodialysis patients and may be a trigger for calciphylaxis due to its role in activating matrix Gla protein (a tissue inhibitor of calciﬁcation). We report the case of a 43-year-old female haemodialysis patient who developed calciphylaxis. Two months prior to the diagnosis she was found to have an undetectable plasma vitamin K concentration. The calciphylaxis completely resolved with vitamin K supplementation and an increase in haemodialysis frequency. She did not receive sodium thiosulphate or bisphosphonates. Supplementation of vitamin K in deﬁcient patients may improve the outcome of this condition. Key words: calciphylaxis, malabsorption, matrix Gla protein, renal dialysis, vitamin K cyclophosphamide followed by docetaxel for breast cancer. Background After docetaxel administration, she developed ischaemic gut Calciphylaxis is a disease of painful, ulcerating, violaceous skin and septic shock, ischaemic hepatitis and became dialysis nodules that progress to subcutaneous tissue necrosis. It usu- dependent. She underwent total colectomy and a 2.3 m small ally occurs in maintenance dialysis patients, is associated with bowel resection with jejuno-rectal anastomosis and received small vessel calcification and carries a high mortality . 2 months of total parenteral nutrition before recommencing Vitamin K is needed to gamma-carboxylate the family of pro- adequate oral intake. teins called gamma-carboxyglutamic acid (Gla) proteins. Matrix Gla One year after the presentation with septic shock, she pre- protein (MGP) is one such protein and, when carboxylated to cMGP, sented with an ulcerating, painful nodular rash over her calf and it acts to inhibit tissue and vascular calcification . Approximately lateral upper thigh. At presentation she was normocalcaemic, half of patients with calciphylaxis are known to be prescribed war- had mild hyperphosphataemia (1.62 mmol/L), her parathyroid farin (a vitamin K antagonist) at disease onset and such patients hormone was 28 pmol/L (reference range<7.5 pmol/L) and she are also known to have a lower fraction of cMGP . received thrice weekly haemodialysis (260 min/session) using a We report the successful treatment of calciphylaxis with 1.25 mmol/L calcium dialysate. She took sevelamer as a phos- high-dose vitamin K. The patient has provided informed con- phate binder and did not take vitamin D analogues or warfarin. sent for the publication of this case report. X-ray of the soft tissue showed diffuse subcutaneous calcifi- cation. Histology of the rash demonstrated mural vascular calci- Case report fication with intraluminal thrombi and fat necrosis. A 43-year-old white female with a body mass index (BMI) of 51 kg/ Immunofluorescence was negative. Serum vitamin K meas- m , received three cycles of fluorouracil, epirubicin and ured using C18 solid-phase extraction and zinc reduction Received: July 12, 2017. Editorial decision: September 25, 2017 V C The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact firstname.lastname@example.org Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/528/4616523 by Ed 'DeepDyve' Gillespie user on 07 August 2018 Calciphylaxis in a dialysis patient | 529 for this reason, vitamin K deficiency is common in the dialysis population . In our patient, this predisposition to deficiency was likely exacerbated by poor absorption secondary to extensive past small bowel resection. The two pathological processes in calciphylaxis are cutane- ous arteriolar stenosis and vascular occlusion. Vascular stenosis occurs insidiously from medial arteriolar calcification and is an active process of vascular smooth muscle cells that is inhibited by cMGP . Vascular thrombosis tends to occur acutely and leads to painful ulceration. Our patient had some classic risk factors for calciphylaxis, such as obesity and female sex. Other traditional risk factors, including PTH and plasma phosphate , actually deteriorated during her recovery, probably secon- dary to stimulation of the parathyroid by the low-calcium dialy- sate. For this reason we believe the trigger for developing calciphylaxis was most likely her severe vitamin K deficiency. Fig. 1. Time course of plasma calcium, phosphate and PTH. All calciphylaxis lesions healed with vitamin K supplemen- tation along with the co-interventions of lowered dialysate cal- followed by high-performance liquid chromatography was<0.3 cium and increased dialysis frequency. It seems likely that, of nmol/L (reference range 0.3–2.6) and her vitamin A level was 0.8 the co-interventions, vitamin K supplementation had the great- lmol/L (reference range 1.6–2.3). est impact on the patient’s recovery. Recovery did not rely on After diagnosis of calciphylaxis, her dialysate calcium was improvements in plasma phosphate or PTH but may have been reduced to 1.0 mmol/L and dialysis frequency increased to four assisted by the increased frequency of dialysis. sessions/week. Intravenous therapy was begun with 10 mg vita- min K and a multivitamin given at every dialysis session. The multivitamin contained retinol 3500 IU, cholecalciferol 5.5 lg, Conflict of interest statement vitamin E 11.2 IU, vitamin C 125 mg, thiamine 3.51 mg, ribofla- None declared. vine 4.14 mg, pyridoxine 4.53 mg, cyanocobalamin 6 lg, folic acid 414 lg, dexpanthenoic acid 17.25 mg, d-biotin 69 lg, niacin 46 mg, glycocholic acid 140 mg and lecithin 112.5 mg. No References bisphosphonate or sodium thiosulphate was administered. 1. Brandenburg VM, Kramann R, Rothe H et al. Calciﬁc uraemic Plasma vitamin K levels rose to 20 nmol/L (reference range 0.3– arteriolopathy (calciphylaxis): data from a large nationwide 2.6). She experienced one episode of bacteraemia prior to complete registry. Nephrol Dial Transplant 2017; 32: 126–132 resolution of all skin lesions 12 months after commencing vitamin 2. Tyson KL, Reynolds JL, McNair R et al. Osteo/chondrocytic K. The time course of plasma calcium, phosphate and intact para- transcription factors and their target genes exhibit distinct thyroid hormone (iPTH) changes are shown in Figure 1.(iPTH was patterns of expression in human arterial calciﬁcation. measured on an Abbott ci16200 analyser with an Architect iPTH Arterioscler Thromb Vasc Biol 2003; 23: 489–494 second-generation assay.) 3. Nigwekar SU, Bloch DB, Nazarian RM et al. Vitamin K-depend- ent carboxylation of matrix Gla protein inﬂuences the risk of Discussion calciphylaxis. J Am Soc Nephrol 2017; 28: 1717–1722 4. Cranenburg ECM, Schurgers LJ, Uiterwijk HH et al. Vitamin K There are two types of natural vitamin K: vitamin K ,which is intake and status are low in hemodialysis patients. Kidney Int found in green vegetables, and K , which is found in cheese, natto 2012; 82: 605–610 and similar fermented foods. Both K and K activate vitamin 1 2 5. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: K–dependant proteins, including MGP. Dialysis patients are often risk factors, outcome and therapy. Kidney Int 2002; 61: advised to restrict their intake of sodium- and potassium- containing foods (such as cheese and green vegetables). Probably 2210–2217 Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/528/4616523 by Ed 'DeepDyve' Gillespie user on 07 August 2018
Clinical Kidney Journal – Oxford University Press
Published: Aug 1, 2018
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