PORTLAND, Ore.—Researchers have discovered the process that could be causing side effects from antirejection transplant drugs, according to a study in Nature Medicine.
A group of researchers led by scientists at Oregon Health & Science University examined the effects of a class of antirejection — or immunosuppressive — drugs called calcineurin inhibitors, which includes cyclosporine and tacrolimus.
Calcineurin inhibitors, which can be instrumental in preventing organ rejection in transplant patients, also can cause hypertension and kidney problems. The researchers’ findings reveal what ultimately causes those problems — a calcineurin inhibitor spurs the production of an abnormally high level of a natural protein in the kidney.
Researchers found that a thiazide diuretic drug, which blocks the responsible protein, reduced hypertension in mice that had been given the calcineurin inhibitor. And mice lacking this protein did not develop hypertension at all.
The collaborative team of researchers, which included scientists from University College London, extended their observations to humans — kidney transplant patients in the United Kingdom.
University College London scientists found that kidney transplant patients who received the calcineurin inhibitor were more sensitive to a thiazide diuretic than were patients treated with other antirejection drugs.
The research results could mean very good news for transplant patients who have hypertension and potassium problems due to the antirejection drugs they’re taking. That’s because the drugs that can combat the elevation of the natural protein are generally the cheapest hypertensive drugs available — but many physicians have not been prescribing them for the side effects because they believed the problems were caused by changes outside the kidney.
"These findings should allow physicians to prescribe these simple drugs much more often and provide help to many, many more transplant patients who are suffering from these side effects," said David Ellison, MD, head of OHSU’s Division of Nephrology and Hypertension and the senior author of the study.
Ellison said the research points the way toward the next question he is planning to look at — taking a deeper look at the mechanism of how the antirejection drugs work. More research in that area might help scientists develop a drug that suppresses the body’s attempt to reject a transplanted organ, but produces none of the hypertension and other side effects, he said.
"That’s my new grant proposal — to take it to the next step," Ellison said.
