Bootcongres

Introduction. Hypocalcaemia is common in chronic kidney disease and is the result of a reduced synthesis of 1,25-dihydroxyvitamin D and the occurrence of hyperphosphataemia. Falsely decreased total serum calcium levels in the absence of an abnormal ionized calcium (iCa) concentration (which is the physiologically active form) is a well-known pitfall, for example in patients with hypoalbuminaemia. Therefore, measurement of iCa concentration, using a Rapidlab-1265 blood gas analyzer is the preferred method in our hospital. However, iCa levels could also be falsely decreased, as we will illustrate in three cases of kidney transplant recipients with BK nephropathy. Cases. We present three cases of kidney transplant recipients with a biopsy proven BK nephropathy. Since reduction in immunosuppressive medication failed to clear the BK viral load, leflunomide was started. Approximately 60 days after leflunomide was started, decreased iCa levels were observed which did not respond to supplementation. The lowest iCa levels measured were 0.74 mmol/l after 176 days in patient 1, 0.75 mmol/l after 148 days in patient 2, and 0.84 mmol/l after 85 days in patient 3. None of the patients had neuromuscular or cardiovascular symptoms. In all patients serum calcium corrected for albumin was in the normal range. Because of the discrepancy between iCa and total calcium corrected for albumin level, falsely decreased iCa levels were suspected. After stopping leflunomide, iCa concentrations returned to normal values without having an effect on total calcium concentrations. Further analysis revealed that teriflunomide, the active metabolite of leflunomide, interferes with the measurement of iCa on Rapidlab-1265 blood gas analyzers. This effect was also seen on point-of-care I-Stat blood gas analyzers, but not on an ABL800-FLEX blood gas analyzers showing that the effect is analyzer-specific.

Conclusion. Leflunomide is a synthetic isoxazole-derivative drug that possesses both immunosuppressive and antiviral properties. It is used in kidney transplant recipients for BK nephropathy. Recent reports have suggested a potential role in the management of ganciclovir-resistant CMV disease in transplant recipients. Our cases illustrate that leflunomide, via teriflunomide, interferes with the measurement of iCa resulting in falsely low iCa . Awareness of this interference and use of total calcium and albumin concentrations could avoid inappropriate and potentially harmful treatment.