Falsely decreased ionized calcium results due to analytical interference by teriflunomide, the active metabolite of leflunomide (Arava?)

摘要

Recently, we found unexpected low ionized calcium (Ca~(2+)) results in kidney transplant recipients. In these patients no clinical signs of hypocalcemia were observed. Despite supplementation, Ca~(2+) results did not normalize. Total calcium and albumin levels were within normal ranges. Therefore, erroneous measurement of Ca~(2+) was considered. Inspection of the Ca~(2+) electrode of our blood gas analyzers (Rapidlab-1265, Siemens Healthcare Diagnostics, Breda, The Netherlands) did not reveal any problems and internal QC results were within the defined ranges. Remarkably, all of these patients were treated with leflunomide (Arava~R; Sanofi-Aventis, Gouda, The Netherlands) for BK virus nephropathy and therefore analytical interference was suspected. Leflunomide is a synthetic isoxazole-derivative drug that possesses both immunosuppressive and antiviral properties. The drug is widely used as a disease-modifying agent for treatment of rheumatoid arthritis. It is also prescribed off-label as an anti rejection drug for solid organ transplantation and for the treatment of polyomavirus BK associated nephropathy in kidney transplant recipients (1,2).