The long-term effect of switching from cyclosporin A to mycophenolate mofetil in chronic renal graft dysfunction compared with conventional management.
BACKGROUND
To overcome toxicity of calcineurin inhibitors, recent trials have proposed substituting cyclosporin (CysA) with mycophenolate mofetil (MMF). No data concerning the long-term side effects and long-term renal outcome of this strategy have been published.


METHODS
We retrospectively compared 39 renal transplant patients with chronic graft dysfunction who were subjected to CysA to MMF substitution (group 1) with 39 matched renal transplant patients who were continued on conventional management (group 2). The mean serum creatinine and the slope of deterioration of renal function before the date of the therapeutic intervention (T(0)) were similar in both groups. Follow-up in both groups was 76 +/- 42 months before T(0) and 44 +/- 11 months after T(0).


RESULTS
In group 1, conversion was associated with a decrease of mean serum creatinine concentrations from 192 to 172 micro mol/l at 1 year (P = 0.004) and 159 micro mol/l at 3 years (P < 0.003) after T(0), whereas it remained unchanged in group 2. The systolic blood pressure decreased in group 1 from 155 mmHg before T(0) to 145 mmHg at 1 year (P < 0.01) and 133 mmHg at 3 years (P < 0.001) without any increase of the antihypertensive drug, whereas it did not change in group 2. Lipid profile tended to improve in group 1 after T(0) and was unchanged in group 2. None of the patients in group 1 developed acute rejection after T(0), whereas two acute rejections occurred in group 2. Graft survival, however, was similar in both groups. In group 1, several side effects occurred related to MMF treatment, and led to its discontinuation in two cases and the reduction of its dose for 18 patients (64%).


CONCLUSIONS
CysA/MMF substitution improves renal function and blood pressure in chronic allograft dysfunction when compared with conventional management. However, CysA/MMF substitution is associated with a high rate of MMF-related side effects, requiring modulation of its dose.
François
Hélène
H
Nephrology Unit and Anatomopathology Unit, 94270 Le Kremlin-Bicêtre and INSERM U542, 94800 Villejuif, France. antoine.durrbach@bct.ap-hop-paris.fr
Dürrbach
Antoine
A
Amor
Mounia
M
Djeffal
Rachid
R
Kriaa
Fayçal
F
Paradis
Valérie
V
Bedossa
Pierre
P
Charpentier
Bernard
B
D000328:Adult; D018376:Cardiovascular Abnormalities / Q000139:chemically induced; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid