Open randomized trial comparing early withdrawal of either cyclosporine or mycophenolate mofetil in stable renal transplant recipients initially treated with a triple drug regimen.
Cyclosporine (CsA) is the current primary immunosuppressant for the prevention of renal allograft rejection. Its chronic use is associated with various adverse effects like hypertension, hyperlipidemia, and nephrotoxicity, which in turn may contribute to chronic allograft nephropathy and cardiovascular mortality. This study compares a CsA-free maintenance regimen of mycophenolate mofetil (MMF) and corticosteroids with CsA and corticosteroids after early conversion from triple drug therapy. Eighty-four renal transplant recipients who had stable graft function on triple drug therapy with MMF, CsA, and steroids were randomly assigned to be withdrawn from either CsA (n = 44) or MMF (n = 40) at 3 mo posttransplantation. Kidney function at 1 yr was the primary endpoint. Secondary parameters of efficacy were patient and graft survival, incidence of acute rejection episodes, BP, and lipids. At study entry, the alternative treatment groups were similar with respect to demographics, renal function, dosage of CsA, BP, and concomitant medication. Both the creatinine clearance (71.7 versus 60.9 ml/min) and calculated GFR (73.2 versus 61.9 ml/min) were significantly better in MMF-treated patients at 1 yr. Conversion to MMF was associated with a decline of systolic and diastolic BP (128/76 versus 139/82 mmHg) and with a more favorable lipid profile. There was no difference in patient survival (100%) and graft survival (97.7% versus 100%). Acute rejection episodes occurred more frequently after withdrawal of CsA (11.3% versus 5.0%), but the difference was NS. Early tapering of CsA can safely be accomplished in renal transplant recipients who are stable on a triple drug regimen with MMF, thereby resulting in improved renal function, a more favorable lipid profile, and beneficial effects on posttransplant hypertension.
Schnuelle
Peter
P
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
van der Heide
Jaap Homan
JH
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
Tegzess
Adam
A
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
Verburgh
Cornelis A
CA
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
Paul
Leendert C
LC
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
van der Woude
Fokko Johannes
FJ
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
de Fijter
Johan W
JW
*University Hospital Mannheim, Ruperto Carola, Heidelberg, Germany; University Hospital, Groningen, The Netherlands; and Leiden University Medical Center, Leiden, The Netherlands.
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D009173:Mycophenolic Acid