Chronic cyclosporine-induced nephrotoxiciy in heart transplant patients: long-term benefits of treatment with mycophenolate mofetil and low-dose cyclosporine.
BACKGROUND
Cyclosporine-induced nephropathy is a major limitation in heart transplant patients. Cyclosporine dose reduction may lead to substantial early improvement in renal function. Our aim was to study the long-term benefits of therapy with low doses of cyclosporine plus mycophenolate mofetil in heart transplant patients with drug-induced nephrotoxicity.


METHODS
Twenty-five adult heart transplant patients with cyclosporine-related nephrotoxicity (mean posttransplant = 41.7 +/- 25.7 months) were included in the retrospective analysis (22 men, mean age = 58.8 +/- 7.9 years.). Patients were switched from azathioprine to mycophenolate mofetil (1 to 3 g/d), followed by a stepwise reduction in cyclosporine dosage (trough cyclosporine level maintained around 100 ng/mL). Renal function was determined by serial measurements of serum creatinine and glomerular filtration rate at 3-month intervals.


RESULTS
With a mean follow-up of 30 +/- 13 months, the baseline creatinine of 2.37 +/- 0.5 mg/dL decreased to 1.59 +/- 0.40 mg/dL (P < .0001). The baseline glomerular filtration rate of 36.77 +/- 10.10 mL/min improved to 54.98 +/- 13.80 mL/min (P < .0001). The cyclosporine level was the unique independent variable associated with renal functional improvement (partial R(2) = 0.4). Within the first 3 months, renal function displayed a rapid improvement after conversion to mycophenolate mofetil (P < .001), reaching a plateau, without further significant improvement over the course of time.


CONCLUSIONS
Cyclosporine-induced nephrotoxicity is not a progressive, irreversible disease. Reduction in cyclosporine exposure by addition of mycophenolate mofetil is useful to achieve long-term renal functional improvement, thereby avoiding chronic renal failure. A unique, significant factor associated with this improvement was the reduction in cyclosporine level.
Sanchez
V
V
Heart Failure Unit, Hospital Doce de Octubre, 28041 Madrid, Spain.
Delgado
J F
JF
Morales
J M
JM
Tello
R
R
Gómez
M A
MA
Escribano
P
P
de la Cámara
A G
AG
de la Calzada
C S
CS
D000328:Adult; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid