Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation.
OBJECTIVE
Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.


METHODS
The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients (GFR 44.9 ' 9.9 mL/min/1.73m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ' 0.42 mg/dL) were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.


RESULTS
At month 12 mean SCr (-0.3 ' 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ' 13.1 mL/min/ 1.73m superset2, p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ' 22 mmHg (p = 0.03).


CONCLUSIONS
Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.
Gerhardt
Thomas
T
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. tm.gerhardt@web.de
Terjung
B
B
Knipper
P
P
Palmedo
H
H
Woitas
R P
RP
Kalff
J
J
Sauerbruch
T
T
Spengler
U
U
D000410:Alanine Transaminase / Q000097:blood; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007165:Immunosuppression Therapy; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000517:prevention & control*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage*
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003404:Creatinine; D000410:Alanine Transaminase; D009173:Mycophenolic Acid; D011241:Prednisone