Originally published by our sister publication Gastroenterology & Endoscopy News
By Gina Shaw
Many of the immunosuppressive medications typically used for recipients of solid-organ transplants have known interactions with nutrients and nutrition support. Understanding these interactions and educating patients about them in an accessible manner can go a long way toward ensuring optimal outcomes, speakers noted during the ASPEN 2024 Nutrition Science & Practice Conference.
“Regimens and life in general get really complicated for these patients,” said Jennifer Gommer, PharmD, an abdominal transplant clinical pharmacist at Duke University Hospital, in Durham, N.C. “Managing the interactions between their medications and their nutrition is one piece of a 50-strategy puzzle. We want to keep it as easy as possible.”
In the early-induction phase of transplant immunosuppression, Dr. Gommer noted, corticosteroids are the only major class of drugs that will affect nutrition support. “Even in transplant programs that call themselves ‘steroid-free,’ patients will get steroids in the OR,” she said. “Even if they just get one big whopping dose, that’s still a big deal because these high doses cause a lot of bone loss. That is underappreciated in transplant patients who may already be coming in malnourished. Osteoporosis and osteopenia are a big problem with many of these patients, so this is something to be aware of.”
Managing nutrition in patients immediately post-transplant should focus on adequate intake for healing and recovery, said Jeanette Hasse, PhD, RD, LD, a transplant nutrition manager at the Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, in Dallas. “Patients’ protein requirements typically are significantly increased during the acute postoperative phase, but their caloric needs will vary,” Dr. Hasse said. “If they are malnourished or have malabsorption, experience complications, or have other issues such as cystic fibrosis, pancreatic insufficiency, or require ECMO [extracorporeal membrane oxygenation], their needs will increase.”
However, nutritional needs will decrease in some patients, including those with hypothyroidism, reduced muscle mass and/or inactivity, she noted.
Maintenance Immunosuppressants: Nutrition Issues and Side Effects
Other immunosuppressive agents used during induction, such as monoclonal and polyclonal antibodies, do not typically affect nutrition support. But that picture changes significantly with maintenance agents. “Most patients will be on multiple drugs to prevent acute and chronic rejection forever, or at least for the life of the transplant,” Dr. Gommer said. “The backbone of these regimens is a calcineurin inhibitor such as tacrolimus or cyclosporine. Many patients receive mTOR [mammalian target of rapamycin] inhibitors, including sirolimus and everolimus; antiproliferatives like azathioprine or mycophenolate; or the newer costimulation blocker, belatacept [Nulojix, Bristol Myers Squibb]; and most still do get steroids.”
Because of post-transplant hyperglycemia, Dr. Gommer added, patients commonly are sent home from the hospital with an insulin correction scale to use if blood glucose is high.
Common side effects from calcineurin inhibitors include neurotoxicity and nephrotoxicity, as well as metabolic side effects such as hypertension and diabetes (Expert Opin Drug Saf 2015;14[10]:1531-1546). “We see a lot of [the latter conditions] with these drugs, as well as early electrolyte abnormalities like hyperkalemia, hypomagnesemia and hypercalciuria,” she said. “All of our transplant patients will deal with at least one of these issues, if not all.”
Dietary management of these side effects can include a low-potassium diet and diabetic diet. “Encouraging magnesium-containing foods may lessen the need for high-dose magnesium supplementation, and some patients also note improvements in gastrointestinal side effects with higher fiber intake,” noted Dr. Grommer adding that “we sometimes cannot overcome these issues with diet alone and will need medication help.”
Even with steroid-free regimens, post-transplant diabetes may persist, she added. “Calcineurin inhibitors by themselves, independent of steroids, reduce the survival of beta cells in the pancreas, so up to 25% of our patients may continue to have diabetes even without steroids. Over time, if we can reduce the dosage of these drugs, we see improvements in [hemoglobin] A1c” (Pract Diab 2019;36:33-35).
Side effects of antimetabolite agents include neutropenia, thrombocytopenia, anemia, gastritis, diarrhea, nausea and hepatitis, Dr. Gommer said (Cochrane Database Syst Rev 2015;12:CD007746). “The biggest physical problem most patients will have with these drugs are the GI side effects, which upwards of 50% of people will experience.” She added that IV mycophenolate has the same incidence of GI adverse effects as the oral product, “so switching the formulation is unlikely to help most patients.”
If patients are experiencing debilitating GI side effects or other issues such as nephrotoxicity and uncontrolled hyperkalemia with antimetabolites, switching to an mTOR inhibitor may be an option, but that comes with its own issues. “This is a common choice for patients with kidney injury, but these drugs can impair wound healing, so a lot of transplant programs wouldn’t even think about using them in early days post-transplant surgery,” Dr. Gommer said. “A significant portion of patients will also experience mouth ulcers, and up to 40% to 50% will experience drug-limiting metabolic problems such as hyperlipidemia, hypertriglyceridemia and even pancreatitis, so this is not popular for a lot of reasons” (Transplant Rev 2014;28[3]:126-133).
Belatacept is the only selective T-cell costimulation blocker approved by the FDA. The drug is indicated for prophylaxis of organ rejection in adults receiving a kidney transplant, but “it’s not indicated for liver, heart or lung transplant,” she said. However, the drug has been expanded to off-label use in non-kidney solid-organ transplants. “It’s the place to go if all else fails with these other drugs. It is delivered intravenously, and it does not have any significant nutritional side effects.”
A Caveat on Supplements
Post-transplant patients should avoid all non-prescribed supplements because manufacturers of these products “do not have to prove their efficacy before being marketed, nor do they have to study drug interactions or side effects,” Dr. Gommer said. “We only learn about drug interactions with supplements because of adverse effects and post-marketing reports. Someone takes something and has a bad event.” Specifically, she pointed to “drug interactions with St. John’s wort, which induces CYP3A4 [cytochrome P450 3A4], increasing metabolism and reducing levels of a lot of drugs, including calcineurin inhibitors and mTORs.”
Patients also should avoid ingesting substances such as grapefruit that cause proven interactions with antirejection medications. “We know [grapefruit] inhibits intestinal and liver CYP3A4 enzymes and dramatically increases levels of tacrolimus, cyclosporine, sirolimus and everolimus,” Dr. Gommer stressed (Foods 2020;10[1]:33).
Drug absorption for all of these agents can be affected by food, she added. “For many patients, high-fat foods decrease absorption and peak levels, but consistency in how the patient takes their medications is the only thing that truly matters unless they have major problems achieving therapeutic drug levels. We do not need to make their diet harder.
“The beauty of the calcineurin inhibitors and mTOR agents is that we can measure how much medicine is in their blood,” she said. “I care that their life is easy and that they are taking their medications at the same time every day. If my patient hasn’t eaten breakfast in 10 years, I’m not going to tell them to start because of the drug they’re on. Do what you’re doing, and we will dose the drugs around it.”
Dr. Gommer reported no relevant financial disclosures. Dr. Hasse reported a financial relationship with Alcresta.