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                        JeffNEWS, August 16, 1994
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Concern That Cyclosporine Is Too Toxic Is Unwarranted, 
Kidney Transplant Study Shows
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"Higher doses may even be vital to preventing rejection of 
transplants."

In one of the largest studies of kidney transplant patients 
in the United States, researchers reported in the August 11, 
1994 _New England Journal of Medicine_ that the long-term use of 
cyclosporine did not result in progressive toxicity to the 
kidney, and that higher levels of the drug maintained over the 
long term may help to stabilize kidney transplant function and 
reduce the incidence of organ rejection. 

Cyclosporine is a drug administered to transplant patients 
to help prevent rejection by the body's immune system. The 
study's findings, gathered by a team of transplant physicians 
and surgeons, challenge the current tendency among medical 
professionals to progressively reduce doses of cyclosporine 
following transplant, a practice based on the belief that the 
drug is toxic to the kidneys.  

"What we've found is that cyclosporine works, it's safe, and 
it can be used long-term," said James F. Burke, MD, director 
of the division of nephrology at  Jefferson and a member of 
the study team. "Our findings not only question the practice 
of lowering doses over time, they demonstrate that downward 
adjustments can even be harmful. What we need to do is to pay 
more attention to the doses and levels of cyclosporine we 
give, to insure the best chances of survival for transplant 
patients."

The study, sponsored by Sandoz Pharmaceuticals Corporation, 
which markets cyclosporine under the trade name Sandimmune (r), 
examined the records of 1,663 transplant patients at six 
centers between 1983 and 1990. Patients were followed for a 
mean period of three years, with some patients followed for up 
to five years. 

Dr. Burke cited two other major findings in the study: Low 
doses of cyclosporine at three months (less than 4 mg per 
kilogram of body weight) were associated with an increased 
risk of rejection in the next three months; and patients with 
a late, first acute rejection (after one year) had a somewhat 
higher incidence of low cyclosporine blood levels than those 
who did not reject.

"We hope that these findings resolve any lingering questions 
among medical professionals about the drug's toxicity," said 
Daniel R. Salomon, MD, a transplant physician at The Scripps 
Research Institute in La Jolla, CA, and a co-author of the 
journal article. "Our conclusion from this study is that 
cyclosporine should not be reduced solely on the assumption 
that its long-term use produces progressive damage to kidney 
function."

Others involved in conducting the study were: John D. 
Pirsch, MD, University of Wisconsin in Madison; Eleanor R. 
Ramos, MD, formerly with Brigham and Women's Hospital in 
Boston, now with University of Florida in Gainesville; Donald 
M. Stablein, PhD, of EMMES Corp. in Potomac, MD; David H. Van 
Buren, MD, of Vanderbilt University in Nashville; and John C. 
West, MD, of Geisinger Medical Center in Danville, PA.


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