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|Year : 2011 | Volume
| Issue : 1 | Page : 51-52
Calcific uremic arteriolopathy while on cinacalcet
E Gonzalez-Parra1, C Martín-Cleary1, J Martin2, A Ortiz1
1 Department of Nephrology, IIIS-Fundacion Jimenez Diaz and Autonomous University of Madrid, Madrid, Spain
2 Our Lady of Sonsoles Hospital, Avila, Spain
|Date of Web Publication||31-Jan-2011|
Department of Nephrology, IIIS-Fundacion Jimenez Diaz and Autonomous University of Madrid, Madrid
|How to cite this article:|
Gonzalez-Parra E, Martín-Cleary C, Martin J, Ortiz A. Calcific uremic arteriolopathy while on cinacalcet. J Postgrad Med 2011;57:51-2
Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe complication in dialysis patients. Therapy aims to control risk factors such as secondary hyperparathyroidism, hypercalcemia and hyperphosphatemia. Cinacalcet (Mimpara) is a calcium-sensing receptor agonist that lowers serum parathyroid hormone (PTH) and calcium and may be beneficial in CUA. ,, Hypocalcemia is an adverse effect occurring in a number of patients. However, the optimal management of cinacalcet-induced hypocalcemia is incompletely understood. Calcium salts and vitamin D supplements are often used, but lowering the dose of cinacalcet and/or increasing the dose of vitamin D is usually adequate. Paricalcitol (Zemplar) is a vitamin D receptor activator that results in less hypercalcemia and hyperphosphatemia than the natural hormone calcitriol (Rocaltrol) and has been used to treat CUA. , Additional risk factors for CUA are diabetes, obesity and the use of oral anticoagulation targeting vitamin K.
We report a case of CUA in a patient following three years of control of severe hyperparathyroidism with cinacalcet and paricalcitol. A 54-year-old woman on hemodialysis for 22 years was neither diabetic nor obese. Hyperparathyroidism was treated with calcitriol until 2005, when serum iPTH was 1661 pg/ml, calcium 9.6 mg/dL and phosphorus 5.6 mg/dL and she started cinacalcet. For the next three years serum calcium and phosphorus levels were most of the time within the 8.4-9.5 mg/dL and 3.5-5.5 mg/dL ranges, respectively [Figure 1]. Soon after starting cinacalcet she was switched to 3 mEq/L calcium dialysate because of a trend towards hypocalcemia and 1.5-2 g/d calcium element as calcium carbonate and paricalcitol were prescribed. iPTH decreased to 122 pg/ml after 18 months on cinacalcet. One year before admission for CUA she underwent mitral valve replacement and started acenocoumarol (Sintrom). Forty-one months into cinacalcet, she developed biopsy-confirmed CUA and died. iPTH was 90 pg/ml.
|Figure 1: Summary of biochemical parameters and treatment with cinacalcet, paricalcitol and calcium carbonate. Dotted red lines indicate KDOQI-recommended targets. More recent KDIGO guidelines have raised the iPTH target to 2- to 9fold over normal values for the laboratory (20-65 pg/ml). Using the latter criterion all iPTH determinations during cinacalcet therapy were within guideline limits. Ca: serum calcium, P: serum phosphorus|
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Case reports suggest that cinacalcet, alone or combined with paricalcitol, may be used to treat CUA. ,, However, our patient developed CUA while on long-term cinacalcet and paricalcitol. Thus, drugs reported to be effective in treating CUA failed to prevent CUA. It is extremely important to explore the underlying features of such cases in order to unravel potential contributors to the fatal outcome as well as to avoid a false sense of security in patients using these drugs.
Our case is the second report of CUA developing in a patient on cinacalcet.  However, the present case is better documentation and has long-term follow-up, thus providing additional insights. In the prior case report there was no information on calcium or vitamin D therapy. Unlike the previous case, the present patient had received cinacalcet for several years and for most of the follow-up our patient presented a calcium-phosphorus product and iPTH within the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO)-recommended targets. ,, Both patients were on oral anticoagulants at the time of CUA.  Case-control studies suggest that calcium-containing phosphate binders are a risk factor for CUA.  We hypothesize that large quantities of dialysate calcium and calcium-containing phosphate binders in an attempt to maintain plasma calcium concentration within guideline recommendations may have set the stage for CUA in the presence of a trigger: acenocoumarol, a drug disrupting anti-vascular calcification homeostasis, even when the patients were taking cinacalcet. The recommended total daily dose of calcium should not exceed 1.5 g/day, but calcium from the dialysate provides an acute high load of calcium that could be more harmful than oral administration of calcium. Indeed, there is a KDOQI recommendation for stopping oral calcium phosphate binders to any patient receiving dialysis on the higher dialysate calcium (3.0 mEq). 
This report raises questions regarding potential long-term risks of certain management strategies for hypocalcemia in patients on cinacalcet. The continuous use of cinacalcet/paricalcitol may fail to prevent CUA.
| :: References|| |
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|2.||Mohammed IA, Sekar V, Bubtana AJ, Mitra S, Hutchison AJ. Proximal calciphylaxis treated with calcimimetic 'Cinacalcet'. Nephrol Dial Transplant 2008;23:387-9. |
|3.||Kyritsis I, Gombou A, Griveas I, Agroyannis I, Retsa K, Agroyannis B. Combination of sodium thiosulphate, cinacalcet, and paricalcitol in the treatment of calciphylaxis with hyperparathyroidism. Int J Artif Organs 2008;31:742-4. |
|4.||Khalpey Z, Nehs MA, ElBardissi AW, Semel M, Tullius SG. The importance of prevention of calciphylaxis in patients who are at risk and the potential fallibility of calcimimetics in the treatment of calciphylaxis for patients with secondary hyperparathyroidism. NDT Plus 2010;3:68-70. |
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