Upstate professor publishes paper on formula for safer dosing of meds after kidney transplants
An Upstate Medical University professor who specializes in organ transplants has published a paper about a new formula to help dose anti-rejection medications that could curb major complications after surgery.
Upstate Professor of Medicine Oleh Pankewycz, MD, together with a team of transplant surgeons, nurse coordinators, students and researchers from the Department of Public Health and Preventive Medicine published a paper in April in the journal Clinical Transplantation entitled: “A new model to determine optimal exposure to Tacrolimus and Mycophenolate Mofetil after renal transplantation.” Pankewycz has spent the last four years studying the most common combination of anti-rejection or immunosuppressive drugs for kidney transplant patients, Tacrolimus (TAC) and Mycophenolate Mofetil (MMF). TAC and MMF are taken by up to 85 percent of kidney transplant patients to ensure the body does not reject the new organ, he said.
“The most commonly used combination of drugs has very narrow therapeutic windows,” Pankewycz said. “Over- and under-dosing are common problems leading to infections or rejection respectively. Prior to this publication, dose adjustments were done ‘blindly’ resulting in frequent adverse events.”
Pankewycz studied data from 110 kidney transplant patients from Upstate. He specifically looked at medication levels in blood samples from those patients. Using a “combined formula” score that considers both TAC and MMF levels, he was able to determine an optimal level of drug exposure. If the “combined formula” score rose above a certain number, patients were more likely to develop an infection or drug-related adverse effects. If that number dropped too low, the patient was more likely to develop rejection or new anti-donor antibodies, which could lead to graft failure. Both scenarios are dangerous and common, he said.
“Now we have this formula where we found an ideal number, a kind of a sweet spot, that gives us a therapeutic guideline considering both drugs,” he said. “In patients taking these two drugs, you obtain a blood level two months after transplant and, depending on the clinical situation, you can alter either the Mycophenolate or the Tacrolimus dose to achieve the optimal level. If for instance, a patient’s Tacrolimus blood level is too high requiring a decrease in dose then the Mycophenolate dose would need to be adjusted in order to maintain an optimal and balanced total immunosuppressive exposure.”
Different people metabolize drugs in different ways, Pankewycz explained, which is why typical dosing methods using height and weight don’t always work for drugs like these. This formula could ease that dosing difficulty and prevent dangerous post-transplant complications, he said.
“There’s been no therapeutic guideline on how to use these drugs in the past,” he said. “But here you have a way to more safely give the correct dosage.”
Pankewycz has worked at Upstate since 2016 and plans to retire in early August. He’s been studying this formula for the last four years comparing Upstate data to previous data sets that he previously noted other institutions. He hopes to continue teaching for Upstate remotely and plans to publish additional papers about this formula.
Caption: Upstate Professor of Medicine Oleh Pankewycz, MD, stands in front of the Upstate Living Donation Legacy Tree.