title: Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study.
abstract: As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.
authors.affiliation: Department of General Surgery and Transplantation, University Hospital Essen, 45122 Essen, Germany. susanne.beckebaum@uni-essen.de
authors.forename: S
authors.initials: S
authors.lastname: Beckebaum
authors.forename: V R
authors.initials: VR
authors.lastname: Cicinnati
authors.forename: C G
authors.initials: CG
authors.lastname: Klein
authors.forename: E
authors.initials: E
authors.lastname: Brokalaki
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Malago
authors.forename: A
authors.initials: A
authors.lastname: Frilling
authors.forename: G
authors.initials: G
authors.lastname: Gerken
authors.forename: C E
authors.initials: CE
authors.lastname: Broelsch
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D003971:Diastole / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007231:Infant, Newborn; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017741:Survivors; D013599:Systole / Q000187:drug effects; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D003404:Creatinine; D009173:Mycophenolic Acid; D016559:Tacrolimus