Cyclosporine C2 monitoring improves renal dysfunction after lung transplantation.
BACKGROUND
Cyclosporine (CyA) toxicity is a potential cause of renal dysfunction, which occurs in 38% of lung transplant (LTx) recipients within 5 years. Reducing CyA to "sub-therapeutic" trough (C0) levels increases the risk of rejection. The 2-hour post-dose concentration (C2) is favored as the best single-point surrogate measure of CyA area under the curve (AUC), which reflects drug exposure. In this investigation we assess the effect of conversion to CyA C2 monitoring on renal dysfunction after LTx.


METHODS
Fifteen patients (M:F = 12:3), aged 47 +/- 14 years (range 28 to 62), 3.5 +/- 2.7 (0.2 to 9.0) years post-LTx, with C0 in the therapeutic range (maintenance 100 to 200 microg/liters) (Behring/EMIT immunoassay) and abnormal renal function, were converted from C0 monitoring to C2 monitoring with dose reductions targeting C2 levels of 300 to 600 microg/liter over a 12-month period.


RESULTS
CyA dose was reduced from 6.4 +/- 7.3 (1.2 to 27.9) to 3.1 +/- 2.7 (0.8 to 9.0) mg/kg/day (p = 0.04), with a reduction in C2 levels from 799 +/- 341 (299 to 1,466) to 390 +/- 148 (195 to 675) microg/liter (p < 0.001). Improvements in serum creatinine (0.20 +/- 0.07 [0.12 to 0.35] vs 0.16 +/- 0.04 [0.11 to 0.22] mmol/liter [p = 0.005]) were maintained during the study follow-up period of 1 year. Only 1 patient developed acute rejection and group mean forced expiratory volume in 1 second (FEV(1)) remained stable (2.4 +/- 1.0 [1.1 to 4.0] vs 2.4 +/- 1.2 [1.1 to 4.6] liters).


CONCLUSIONS
C2 monitoring is a practical method of improving renal dysfunction that allows safe dose reductions of CyA when formal AUC monitoring is not feasible. Extended use of this strategy is associated with long-term benefits.
Glanville
Allan R
AR
Lung Transplant Unit, St. Vincent's Hospital, Sydney, NSW, Australia. aglanville@stvincents.com.au
Morton
Judith M
JM
Aboyoun
Christina L
CL
Plit
Marshall L
ML
Malouf
Monique A
MA
D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine