To shuffle things around here, this week's post is a few shorter lists on the medical and scientific aspects of transplantation rather than a single long essay on the social and political aspects. The first two are original to the best of my knowledge, so please use a citation or reference when using them.
Six Basic Causes of Transplant Organ Dysfunction
Regardless of the organ, the fastest way to panic for anyone with a transplant, and the most important problem in transplant medicine, is a sign that the transplanted organ isn't functioning properly. A specific list of all the possible causes would be long and vary by organ, but the problems can be broken down into six general categories that applies across all organs.
- Acute rejection
- Chronic rejection
- Recurrent disease
- Vascular issues
- Drainage issues
Even though acute rejection rates are decreasing, acute rejection is still the "classic" problem in organ transplantation, and without immunosuppression, or if left unchecked, it will still destroy almost any transplant (the exceptions are fascinating, but few and far between). So, even if it's not all that common anymore, it still has to be first on the list.
In kidney transplantation, it's called chronic allograft nephropathy. In liver transplantation, it's called vanishing bile duct syndrome. In heart transplantation, it's called accelerated graft coronary artery disease. In lung transplantation, it's called bronchiolitis obliterans syndrome. Regardless of the organ, it is marked by "obliteration of lumens" of tubes in the transplanted organ, both blood vessels and other tubes. There are very few treatments for most cases of chronic rejection, and it's one of the most feared long-term problems in transplantation, so it has a permanent spot on the worry list.
Almost every patient must take immunosuppressive medications to prevent the immune system from recognizing the transplanted organ as foreign and attacking it (rejection). Unfortunately, since the immune system is responsible for handling infections, suppressing it limits this ability, and transplant patients are susceptible to infections, Specifically, unusual infections are more likely, and the transplanted organ can either be a source of infection from the donor, or more susceptible to infections than usual given all the manipulation it's experienced. Recently, infections exceeded rejection as a cause for hospitalization post-transplant.
Something happened to cause the need for an organ transplant, and in many cases, that condition may still be in play after transplantation. Autoimmune diseases of any organ can recur--for some diseases and organs this is extremely common. Metabolic diseases (such as diabetes) may still be present and unaffected by the transplant. Finally, damage to organs other than the one being transplanted may affect the transplant, such as bladder damage related to kidney diseases and transplants or heart damage related to lung diseases and transplants.
Connecting blood vessels is the first step in every transplant operation, and I've heard transplant surgery described as "vascular surgery with immunology" (immunology accounting for most of this list!). Blood vessels that have been operated on can develop clots, stenosis (narrowing), or leaks and bleeding early or late after transplants. This category may be a bit more "elementary" than the others, but can be just as damaging if not more so. It's easy to check for, and often can be fixed, so shouldn't be forgotten.
Every transplanted organ except the heart has some form of "drainage" or a non-vascular connection. For kidney transplants, it's the ureter. For pancreas transplants, it's the pancreatic duct. For liver transplants, it's the bile duct. For lung transplants, it's the airway. These are often the last "connection" made in a transplant operation, and possibly the least often considered, but they shouldn't be forgotten.
Like many people, I've spent too much time thinking about what I'd wish for if a genie came out of a magic lamp and granted me three wishes. But unlike most people, in my dreams it's the transplant genie, and I've thought of three things that would improve the prospects of everyone needing organ transplants.
- Highly effective treatment for chronic rejection
- A method to eliminate the need for immunosuppression
- An unlimited source of replacement organs
Chronic rejection exists for every transplanted organ, and there are few or no effective treatments for it under most circumstances. The inevitability and inexorability of chronic rejection are what keep transplantation limited to being a treatment for end-stage organ failure rather than a cure.
Immunosuppression is necessary in almost all transplants, and carries the universal risks of infection and cancer, in addition to specific side effects of each drug available. The complications of immunosuppression are often like a separate disease, which leads many to describe transplantation as "trading one disease for another." Without the need for immunosuppression, this other disease could be cured as well.
Finally, As long as I'm dreaming, we may as well get rid of that pesky donor shortage. The need for donated human organs and the relatively short supply of them limits transplantation to a fraction of those who could benefit from it. While increasing organ donation is essential, many estimate that even utilizing all eligible organs will leave a shortfall. Xenotransplantation (using organs from animals), genetically engineering animals to make them more compatible with humans, tissue engineering, and mechanical artificial organs are all strategies and research areas that may make this wish come true.
- Reduce immunosuppression whenever possible.
- Adopt a strategy to prevent noncompliance.
- Monitor renal function closely.
- Perform biopsy early and often to detect late acute rejection.
- Aggressively treat hyperlipidemia.
- Aggressively treat hypertension.
- Do everything possible to encourage patients to quit smoking.
- Screen for breast, cervical, prostate, colorectal, and skin cancer.
- Immunize against influenza and pneumococcal pneumonia.
- Consider prophylaxis with aspirin, calcium, and hormone replacement therapy.