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Conversion of kidney-transplant recipients from calcineurin inhibitors to mTOR inhibitors has been suggested to be a risk factor for increased alloimmune response. We have analyzed the development of new HLA-antibodies (HLA-Abs) early after conversion in 184 patients converted in stable phase at our hospital and compared with a control group of nonconverted comparable 63 transplants. Using single-antigen solid-phase immunoassay analysis, a preconversion and a 3–6 months postconversion sera were prospectively analyzed in every patient for the appearance of new HLA-Abs. Renal function at 2 years postconversion and cumulative graft survival were compared between groups. In 16 patients, new HLA-Abs (3-DSA and 13-NonDSA), not present at the moment of conversion, were detected (8.7% vs. 3.1% in the control group). The type of mTORi used, type of CNI preconversion, the presence of steroids, time of conversion, or indication for conversion did not have influence on this effect but the presence of HLA-Abs before conversion highly correlated with the appearance of new specificities. Patients with de novo HLA-Abs showed a trend to worst graft function and survival. In conclusion, conversion to mTORi can be followed by early appearance of de novo HLA-Abs, especially in patients with HLA-Abs preconversion, and this complication should be screened early after conversion.