Analysis of liver function in renal transplant recipients undergoing C2-monitoring for cyclosporine.
There exists no systematic evaluation of liver function in renal allograft recipients undergoing C2-monitoring with Neoral [cyclosporine A (CsA)-microemulsion]. In the present cohort analysis, we compared the hepatic profiles of C2-monitored (n = 80), C0-monitored (n = 81), and non-CsA-treated renal allograft recipients (n = 29), transplanted between 1/1999 and 2/2004 in our institution. While the C2-targets were set in accordance with (n = 72) or below (n = 8) the consensus on Neoral (1500 +/- 200 ng/ml), non-CsA-patients received FK506 (n = 29), partially in combination with rapamycin (n = 13) as primary immunosuppression. Analysis of maximum hepatic laboratory parameters and also repeated measures by anova within 30 days post-transplant revealed highly significant elevations of direct, indirect and total bilirubin, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase (P < 0.001) in the C2-group, in comparison with the C0- and the non-CsA-group. Bilirubin-levels were by far the most affected of all hepatic parameters, and correlated with C2-levels (r2 = 0.62). Seventeen CsA-patients had excessive bilirubin-elevations (>4 mg/dl) and were therefore considered to be 'CsA-sensitive' [14 C2-patients (17% of all C2-patients), 3 C0-patients (4% of all C0-patients)]. Bilirubin- and the other parameter elevations in these patients were reversible upon withdrawal or lowering of CsA. Most 'CsA-sensitive' patients (n = 12, 70%) displayed pre-transplant hepatic impairment, indicating a pre-existing liver instability. Collectively, our data emphasize the need for increased awareness toward individual predispositions for CsA-sensitivity.
Hecking
Manfred
M
Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria. manfred.hecking@meduniwien.ac.at
Kainz
Alexander
A
Schillinger
Martin
M
Posch
Christian
C
Birsan
Tudor
T
Rasoul-Rockenschaub
Susanne
S
Böhmig
Georg A
GA
Schmaldienst
Sabine
S
Watschinger
Bruno
B
Hörl
Walter H
WH
Mühlbacher
Ferdinand
F
Säemann
Marcus D
MD
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin