Budapest, Hungary — Switching renal transplant recipients from azathioprine to mycophenolate mofetil for long-term immunosuppression significantly reduced UVA photosensitivity in a crossover study.
This is likely to decrease the extraordinarily high rate of cutaneous squamous cell carcinoma (SCC) that renal transplant patients experience, Dr. Günther Hofbauer said at the annual congress of the European Society for Dermatological Research.
The medication switch did not affect glomerular filtration rate, urine protein-to-creatinine ratio, or other measures of allograft function, added Dr. Hofbauer of the University of Zurich.
SCC is the most common cancer in solid organ transplant recipients, with a 65- to 250-fold greater incidence than in the general population.
In response to the observation by other investigators that direct DNA damage occurs in response to azathioprine, Dr. Hofbauer and his coworkers measured photosensitivity to UVA and UVB in 16 kidney transplant recipients on long-term azathioprine and 17 on mycophenolate mofetil (CellCept).
They found that the mean minimal erythema dose for UVA in the azathioprine group was 21 J/cm
To follow up on this finding, the investigators conducted a switch from azathioprine to mycophenolate mofetil in 23 stable patients who had received a donor kidney a mean of 14.5 years earlier. Their minimal erythema dose for UVA on azathioprine was 16 J/m
Azathioprine is a mainstay immunosuppressant given to prevent graft rejection in many types of transplant recipients. It is now known to cause selective UVA photosensitivity in the 320- to 400-nm wavelengths, with resultant incorporation of 6-thioguanine (6-TG)—the drug's active metabolite—into the DNA of all cells in the body. The 6-TG absorbs UVA, with the resultant production of reactive oxygen species capable of damaging DNA, Dr. Hofbauer explained.
The mean 6-TG level contained in the patients' peripheral white blood cells dropped from 99 pmol/mg of total DNA while on azathioprine to 43 pmol/mg after 3 months on mycophenolate mofetil. A particularly striking finding, he said, was that the steeper the decline in DNA 6-TG, the greater the increase in the minimal erythema dose for UVA.
“The 6-TG levels didn't drop to 0, so we have reason to believe that 6-TG stays in the system for much longer than our 3-month washout period,” he continued.
Study participants were typically on about 50 mg/day of azathioprine and were switched to 500 mg of mycophenolate mofetil twice daily.
“Our nephrologists say that dose of mycophenolate mofetil actually provides slightly greater immunosuppression, which should, if anything, decrease the rejection rate,” said Dr. Hofbauer, who had no conflicts of interest relevant to his presentation.
This drug is likely to decrease the high rate of cutaneous SCC that renal transplant patients experience.
Source DR. HOFBAUER