Cyclosporine C 2 Levels in De Novo Renal Allograft Recipients: A German Multicenter Prospective Observational Study

Abstract

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C 0) and 2-hour postdose (C 2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients ( n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C 2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 ± 391.9; days 7 to 10: 939.1 ± 422.8; days 14 to 28: 1116.3 ± 497.6; 3 months: 905.0 ± 316.8; and after 6 months: 787.0 ± 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C 2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 ± 115.1; days 7 to 10: 306.7 ± 134.8; days 14 to 28: 382.5 ± 164.7; month 3: 501.5 ± 168.8; month 6: 512.7 ± 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 ± 19.0 mL/min, 22.6% and 59.5 ± 20.7 mL/min, and 17.6% and 67.7 ± 23.5, respectively. In conclusion, mean C 2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.