title: Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-up.
abstract: Because recent large studies have demonstrated that mycophenolate mofetil (MMF) is superior to azathioprine (AZA) as a post-transplant immunosuppressant, it has been speculated that MMF could have a cyclosporin (CsA)-sparing effect in renal transplant recipients with chronic allograft dysfunction. Between April 1996 and October 1998, 31 patients with chronic allograft dysfunction were assigned to have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and graft outcomes were analysed. Mean follow-up time after MMF conversion was 27+/-11 months. Serum creatinine concentration (sCt) significantly decreased after conversion and remained stable at the end of follow-up (227+/-31 micro mol/l vs. 185+/-50 micro mol/l; P<0.0005). Mean variation in sCt was -24% after conversion, whereas it was +20% in the year before conversion ( P<0.001). There was a significant inverse relationship between proteinuria at baseline and improvement in renal function (r=-0.35; P=0.01). Proteinuria increased during follow-up (0.79+/-0.6 vs. 1.79+/-1.08 g/day; P=0.04). Isolated CsA nephropathy was associated with the best outcome. Renal function significantly improved in patients with grade 1 chronic rejection and remained stable in patients with grade 2 chronic rejection. Two patients (6.5%) experienced late acute rejection, respectively 13 and 24 months after CsA withdrawal. Eight patients (29%) experienced systemic infections requiring hospitalization. Blood pressure control and lipid profile improved after conversion. CsA withdrawal with a concomitant switch from AZA to MMF allows a substantial and durable improvement in renal function. Both allograft histology and proteinuria at baseline are predictive of the evolution of renal function after conversion. Physicians should consider the risk of over-immunosuppression possibly associated with this therapeutic strategy.
authors.affiliation: Department of Nephrology, Dialysis, and Renal Transplantation, Hôpital Saint-Jacques, 2, Place Saint-Jacques, 25030, Besançon, France. dducloux@chu-besancon.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
authors.forename: Gérard
authors.initials: G
authors.lastname: Motte
authors.forename: Claude
authors.initials: C
authors.lastname: Billerey
authors.forename: Catherine
authors.initials: C
authors.lastname: Bresson-Vautrin
authors.forename: Pierre
authors.initials: P
authors.lastname: Vautrin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rebibou
authors.forename: Yves
authors.initials: Y
authors.lastname: Saint-Hillier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chalopin
mesh_terms: D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine