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The Ultimate Gift
A
newsletter from the transplant team
at Rhode Island Hospital
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Tacrolimus versus Cyclosporine
(Calcineurin Inhibition)
by Paul Morrissey, MD
Approximately 95 % of renal transplant recipients in our practice
are managed with either tacrolimus or cyclosporine. The major causes
of late allograft failure are chronic rejection, noncompliance and
death with function. In this issue of The Ultimate Gift, the pros
and cons of these two agents are reviewed and two new research studies
in this area are described.
Beginning in June 2005 we began using tacrolimus as our primary
immunosuppressant replacing cyclosporine (Neoral). Among the reasons
for this change were the following:
- Meta-analysis showed superior efficacy
- Lower incidence of chronic allograft nephropathy
- Possibly less nephrotoxicity as shown in healthy human subjects
- No cosmetic side effects—gingival hyperplasia and hirsuitism
- Less hyperlipidemia
- Trough level correlates with drug exposure—allows simplified
monitoring
- Requires smaller doses of MMF (500 BID versus 1000 BID = cost
savings)
- Smaller pill, no odor.
Over the one-year period (June 2005-May 2005) 82 patients were
transplanted. Among these patients there were 6 episodes of acute
rejection (7 %). Currently, 78 of the transplants are functioning.
New Studies
Patients with evidence of chronic rejection (chronic allograft
nephropathy) should be referred for evaluation. Signs of chronic
allograft nephropathy include worsening BP control, proteinuria
and a rise in creatinine ("creatinine creep"). In general,
a creatinine rise of greater than 30% or 0.5 mg/dl should be investigated.
Evaluation consists of Chem 7, CBC, UA, U protein/creatinine ratio,
Doppler ultrasound and biopsy. Patients who undergo biopsy are candidates
for a trial of:
- calcineurin inhibitor dose reduction, versus
- conversion to sirolimus (Rapamune)
A second study "OPTIMA: Optimizing Prograf Therapy in Maintenance
Allografts" will begin in December 2005. Patients who are on
cyclosporine will be randomized to:
- remain on cyclosporine (trough 50-250 ng/ml)
- convert to Prograf (trough 3-5.9 ng/ml), or
- convert to Prograf (trough 6-8.9 ng/ml).
Outcomes include renal function at 6, 12, 24, 36 months,
incidence of rejection, TGF-beta, CRP and homocysteine levels, and
safety endpoints (hyperlipidemia, cardiac events, hypertension,
diabetes, etc.).
Thank you for this opportunity to update you on the care of your
patients.
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