Today, kidney transplantation provides patients with invaluable benefits—it prolongs lifespan and restores vitality and health. However, this hasn’t always been the case. As recently as the 1980s, results of transplants were fairly poor, and kidneys were often lost from rejection. In 1983, the cyclosporine class of drugs entered the equation, revolutionizing transplantation. Short-term outcomes improved greatly, and we expected most of our patients to survive with a functioning graft—90% of them at the 1-year mark.
Unfortunately, while cyclosporine is ideal for short-term outcomes, it causes many side effects that affect long-term outcomes in patients. Cyclosporine is toxic to the kidney—over time, this causes excess scarring and eventually even leads to loss of kidney function.
In approximately one-third of patients, cyclosporine causes post-transplant diabetes, requiring most patients to take blood pressure lowering medications. Additionally, most must take medications to lower their cholesterol. (High blood pressure and increased cholesterol counts are both side effects of cyclosporine.) Ultimately, patients must take the anti-rejection drugs along with a host of other drugs to combat the side effects, all of which can lead to death from cardiovascular disease. On average, the kidney transplant patient survival rate is only 8-10 yrs, which is clearly short of what we’d like to see.
Sufficed to say, there’s been a tremendous need for better drugs to prevent rejection in kidney transplants, without causing life-threatening side effects.
When kidney patients suffer from transplant rejection, the immune system essentially recognizes the new kidney as a foreign object, causing lymphocytes and T-cells to attack, and generating immune damage to the transplant. Consequently, we introduce drugs to dampen the immune system. The issue with cyclosporine is that it doesn’t just affect the immune response; it hits several other targets throughout the body, causing the negative side effects. Fortunately, there’s hope on the horizon with a newer drug called belatacept.
Like Cyclosporine, belatacept blocks the immune system from transplant rejection. However, the target of belatacept is only expressed in the immune system, so it suppresses undesired immune responses of rejection without the off target side effects (e.g. high blood pressure, increased cholesterol and diabetes) seen with Cyclosporine. We refer to these off-target responses as “costimulatory signals”.
In transplantation, our goal is to achieve a normal life span for our patients, and to ideally have them move on from surgery dialysis-free. At Emory, we’ve dedicated years to developing new and improved therapies that avoid major complications from kidney transplants, including cardiovascular issues, infections and malignancies.
Recent belatacept studies indicate that this drug could quite possibly help us in achieving these goals. Over 1400 patients have been studied with belatacept’s use in kidney transplant, and the results continue to be extremely promising. Further, the drug could conceivably have advantages for other types of organ transplantation, including liver, heart, lung, and intestinal.
Do you have any questions about belatacept, or about kidney transplantation in general? If so, please let me know in the comments.