Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study.
BACKGROUND
Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant monitoring, but should be further explored in thoracic organ recipients.


METHODS
In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively. Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based on 2-week post-operative values (tertiles T1 to T3).


RESULTS
C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any rejections (p = 0.001) and time to first rejection (p = 0.03) between T1 and T3. C2 did not predict reduction in mGFR.


CONCLUSIONS
C2 is a sensitive predictor for ACR in lung, but not heart, recipients, C2 was not predictive of a decline in mGFR. This study suggests that management of lung recipients by C2 may diminish the number of ACRs.
Iversen
Martin
M
Department of Cardiology, Section of Heart and Lung Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. martin.iversen@dadlnet.dk
Nilsson
Folke
F
Sipponen
Jorma
J
Eiskjaer
Hans
H
Mared
Lena
L
Bergan
Stein
S
Nyström
Ulla
U
Fagertun
Hans E
HE
Solbu
Dag
D
Simonsen
Svein
S
D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000601:surgery; D003324:Coronary Artery Disease / Q000601:surgery; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000601:surgery; D004646:Emphysema / Q000601:surgery; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016040:Lung Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine