What are anti-rejection drugs and why seek to eliminate them?

Normally, a kidney transplant recipient’s immune system sees the donated kidney as foreign and will attack it–a process called rejection. To prevent this process, anti-rejection medicines are used to suppress the transplant recipient’s immune system. Kidney transplant recipients require a lifelong, daily regimen of anti-rejection drugs. Although anti-rejection medicines are very effective at preventing rejection of kidneys, particularly in the first several years following the transplant, there are multiple side effects and tolerability issues that affect recipients’ ability or willingness to take these medicines, ultimately adversely affecting long-term outcomes for donated kidneys and recipients.

A standard anti-rejection regimen typically includes a high dose immunosuppressant drug administered in the hospital at the time of transplant called induction therapy, followed by lifelong, daily maintenance treatment typically with tacrolimus (brand name Prograf), mycophenolate mofetil (also known as MMF or by the brand names CellCept or Myfortic), and a corticosteroid (usually prednisone). Many kidney transplant recipients take more than 20 pills per day as part of their lifelong anti-rejection regimen. Because these medications suppress the entire immune system, transplant recipients must be very careful to avoid potential infections for as long as they are taking anti-rejection medicines. Recipients must give up certain types of food entirely. Neurological side effects, such as tremors, depression, and impaired cognition are common. Over time, the toxicity of these drugs causes a decline in kidney function, as well as damage to other organs. As kidney function declines, patients will feel less well. The average life of a transplanted kidney is between 12 and 20 years. Roughly 1/3 of living donor kidney transplants and roughly half of deceased donor kidney transplants fail within 10 years. The leading cause of transplant failure is chronic rejection of the kidney (despite treatment with anti-rejection medicines).

Additionally, within ten years after transplant, many patients on anti-rejection medicines have significantly higher rates of high blood pressure, diabetes, high cholesterol, high triglycerides and weight gain, resulting in a higher risk of cardiovascular events. Many patients have to take multiple medicines to manage these life-threatening cardiovascular and metabolic side effects. Patients who take corticosteroids chronically are susceptible to loss of bone density, which increases risk of fractures. Within 15 years, kidney failure and the need for dialysis or another transplant are common. Chronic treatment with anti-rejection medicines has also been linked to a significantly higher risk of certain types of cancer than for the general population. The ongoing cost and decreased quality of life associated with chronic treatment with anti-rejection medicines also leads some recipients to stop taking them, thus increasing their risk of kidney rejection.