The Uniform Anatomical Gift Act lets a person or family give permission to donate any organs.9 “Domino” transplants can be used to increase the number of transplants for recipients who have a nonmatching donor.10 By using a system that trades kidneys between donors and recipients nationwide, with or without an altruistic donor in the chain, a domino-effect transplant chain can be created. This lets more patients have living donor transplants, the preferred type of kidney transplant.6
Deceased donor kidneys are assessed based on several factors, including age, ethnicity, history of hypertension or diabetes, HLA antibodies, blood type, and serum creatinine. An ECD kidney is defined by age and/or comorbidities and offered to all recipients with emphasis on the older kidney patient. For kidneys, ECD donation is defined as:
- donors over age 60 years
- donors ages 50 to 59 years with one or more of the following: stroke as cause of death, history of hypertension, or serum creatinine greater than 1.5 mg/dL at time of death. As of July 2014, the ECD/SCD system has been fully replaced by the kidney donor profile index (KDPI) for all kidney transplants in adults.7
The deceased donor kidney is assigned a KDPI that rates kidney quality from highest to lowest projected longevity. The lower the percentage, the longer the expected life of the kidney.7 This percentage is then used to allocate donor kidneys to recipients based on the recipients' projected life expectancy as calculated with age, comorbidities, and time on dialysis.11 The recipients with the highest life expectancy receive the higher-survival KDPI-scored donors and vice versa. Providers may access the KDPI at the OPTN website to review factors used to rank deceased donor kidneys.
The recent passage of the HOPE (HIV Organ Policy Equity) act lets HIV-positive donors donate to HIV-positive recipients.12 Previously, HIV-positive donors could not donate, even if the recipient was HIV-positive. Patients with hepatitis B and C are listed for kidney transplants and are offered hepatitis-positive organs.6 Recipients who receive kidneys from live donors have longer graft survival than those patients receiving kidneys from deceased donors. The 10-year graft survival rate is 57% for recipients of living donor kidneys versus 41% for those who received kidneys from deceased donors.8
Acute postoperative complications of kidney transplant (whether living or deceased donor) include urine leaks, ureteral obstruction, vascular complications, and delayed graft function. Urine leak is the most common technical complication following transplant, occurring in 9.3% of patients; delayed graft function is the most common acute complication.6 Delayed graft function, which occurs in 21.3% of posttransplant patients, has several definitions but most often is defined as the use of dialysis within 7 days of transplant. Factors that place the recipient at risk for complications include obesity, diabetes, age over 55 years, male sex, and African American race. Once other causes of kidney dysfunction are excluded, patients should undergo kidney biopsy to assess for acute rejection. Studies have shown that delayed graft function does not have a negative effect on long-term graft survival.6
The ultimate complication is acute rejection. Induction therapy uses strong antirejection medications such as thymogloblin, alemtuzumab, and basiliximab and follows a transplant center–specific protocol peritransplant to decrease T-mediated cell proliferation and organ rejection.13 Despite the use of induction therapy and immunosuppressive agents, acute rejection still can occur; however, the incidence has been decreasing, and fewer than 15% of posttransplant patients develop acute rejection.6 Suspect organ rejection if the patient's creatinine is rising. A kidney biopsy confirms the diagnosis.
Recurrent disease may also occur at any time posttransplant, causing renal graft failure. The most frequent causes of recurrent renal disease are focal segmental glomerulosclerosis (20% to 50% of cases), IgA nephropathy (13% to 53%), lupus nephritis, membranous glomerulonephritis, and diabetic nephropathy.6 However, despite the potential complications, kidney transplantation becomes more successful each year, and can benefit many patients.
In 1963, the first liver transplant was performed by Dr. Thomas Starzl at the University of Colorado. The recipient was Bernie Solis, a 3-year-old dying of biliary atresia.14 Unfortunately, Bernie died in surgery due to portal vein and clotting issues. Dr. Starzl's first successful liver transplant was later that year, although the patient only lived 22 days posttransplant. The clotting difficulties with the intraoperative external bypass posed the main obstacle to successful and commonplace liver transplants.
Alcohol abuse is the most frequent cause of adult liver failure, and a patient who is consuming alcohol cannot be placed on the active transplant waiting list.15 Patients whose alcohol abuse has caused liver failure cannot get a new liver if they are actively drinking. The restrictions depend on the transplant center, but usually patients must abstain from alcohol for 1 to 3 years.
In the United States, the most common diagnosis for patients on the liver transplant waiting list is hepatitis C, followed by acetaminophen toxicity and medication-induced liver failure.16,17 Inclusion and priority on the liver transplant list is calculated by Model for End Stage Liver (MELD) score or Pediatric End State Liver (PELD) score; pediatric is defined as a patient under age 12 years.18 The MELD/PELD scores include specific hard data (dialysis two times in the last week, serum creatinine, bilirubin, and international normalized ratio) and are scored from 6 to 40.19 Although dialysis will move a patient up on the liver transplant list with a higher MELD score, few patients in need of a liver transplant are on dialysis. A higher score lets a patient receive a transplant sooner. Recently, controversy has arisen as to whether the sickest patients may be too sick to benefit from a liver transplant. However, OPTN does not plan to change the liver scoring for 2014.20
Liver transplants can be obtained from deceased or living donors. The right lobe of the liver is transplanted from a living donor to the recipient. In a deceased donor, the liver may be split at the time of procurement into two lobes, or the entire liver may be transplanted into one recipient. If the liver is split, the smaller lobe is often transplanted into a child.21 Extended criteria donor livers also are transplanted (Figure 6).22 For liver transplants, ECD is defined as:
- donors ages 70 to 80 years
- donors older than age 60 years with a significant medical history
- donors with a history of high-risk social behaviors
- donors with a history of hepatitis B or C exposure.
Hearts are the third most often transplanted organ. Dr. Christiaan Barnard performed the first heart transplant in 1967 in South Africa. The recipient, Louis Washkansky, died 22 days after the transplant due to pneumonia from immune system oversuppression secondary to antirejection drugs.23
Although heart failure continues to be the main cause of cardiac death, many patients with heart failure are too old or too sick to undergo a heart transplant. The most common causes of listing patients for a heart transplant are cardiomyopathy, congenital heart disease, and ischemic and/or valvular heart disease.24
Heart transplants from deceased donors can be a single organ, or part of a combination heart/lung transplant. Transplants can be single (native heart removed and donor heart placed), heterotopic (native heart is not removed and donor heart placed), or part of a domino heart transplant. A domino heart transplant occurs when a patient needing a lung transplant undergoes a heart/lung transplant. This patient's native heart is then transplanted into a second recipient in a domino fashion.25
The development of heart devices has revolutionized heart transplants.26,27 Dr. Denton Cooley implanted the first artificial heart at the Texas Heart Institute in 1969; today, vascular assist devices (VADs) developed as bridges to heart transplantation are the more common approach. Willem Johan Kolff (the father of the first dialysis machine) developed the first VADs in the 1970s. The Jarvik 7, developed at the University of Utah in the Kolff laboratory, was the first implantable artificial heart pump designed for long-term use. Intra-aortic balloon pumps (IABPs) and extracorporeal membrane oxygenation (ECMO) are also common bridges to heart transplantation.28,29 Having a VAD or being on ECMO or an IABP will move a patient higher on the transplant list.20
A patient with a VAD (right, left, or bivalve) no longer must wait in the hospital for a heart transplant. Although a heart assist device will classify a patient as a higher priority for transplantation, hospitalization has been dropped from the priority rankings.30 Patients who do not have heart assist devices remain at lower priority on the transplant list.
Dr. James Hardy performed the first lung transplant at the University of Mississippi in 1963.31 In 2013, the most common cause for needing a lung transplant was cystic fibrosis in children and chronic obstructive pulmonary disease (COPD) in adults.32,33 Lung transplants can be from deceased or living donors. Adults over age 65 years accounted for the largest growth in adult candidates for transplant in 2011.32
The first living lung transplant occurred in 1990; living donor transplants are not as common as those from deceased donors, and some transplant centers do not perform lung transplants from living donors.34 In a living donor lung transplant, a lung lobe is removed from the donor and transplanted into the recipient.
Lung transplants are scored via the Lung Allocation Score (LAS), which is used for patients over age 12 years.35 A change in the LAS in 2005 has led to a decrease in the number of patients who die while on the waiting list, but posttransplant deaths also have increased.36 The increase in a patient's LAS score right before transplant seems to be the most predictive factor in death after lung transplant; thus, serial measurements are encouraged.
An LAS score includes:
- wait list urgency measure—the expected number of days a candidate will live without a transplant during an additional year on the waiting list
- posttransplant survival measure—the expected number of days a candidate will live during the first year posttransplant
- transplant benefit measure—the difference between posttransplant survival and wait list urgency measure
- raw allocation score—the difference between transplant benefit measure and wait list urgency measure.
The items used to predict survival include, but are not limited to, pulmonary artery pressure, diagnosis, diabetes, forced vital capacity, age, body mass index (BMI), serum creatinine, 6-minute walk distance, mechanical ventilation, and functional status. Grouping classification for transplant is done by diagnosis. As of January 1, 2014, just over 1,600 patients were on the lung transplant waiting list (Table 1).2
William Kelly and Richard Lillehei at the University of Minnesota led the way for both pancreas and pancreas/intestine transplants.37 They transplanted the first pancreas in 1966, the first pancreas/intestine in 1968, and the first pancreas islet in 1990.
The number of pancreas transplants has been decreasing since 2000 and reached a nadir in 2011, the last year for which data are available.38 Outcomes are improving annually for all types of pancreas transplants: simultaneous kidney/pancreas transplant, pancreas alone, and pancreas after kidney transplant. This improvement may be due to better immunosuppression, better surgical technique, or better donor-recipient selection, or a combination of the three.39 The number of patients on the pancreas transplant waiting list is decreasing; 90% of these patients have type 1 diabetes.38 The decreased interest in pancreas transplants may be due to better insulin regimens and increased BMI in patients with diabetes (a stumbling block for listing).
Islet cell transplants alone may be offered in a research setting. These are not part of the UNOS data on solid organ transplants. In islet allotransplantation, islet cells from deceased donors are extracted and implanted into the recipient. However, the limited number of appropriate pancreases recovered from deceased donors (1,562 in 2011) meant that few islet cells were available for transplant.38 Not uncommonly, more than one pancreas is needed for each islet cell transplant and the transplant community is hesitant to sacrifice more organs for fewer recipients. Funding poses a major obstacle to islet cell transplants. Currently, islet cell transplants are considered experimental and are not covered by insurance. The National Institutes of Health (NIH) has ongoing studies to work toward FDA approval of islet cell transfers.39 Both Canada and Scandinavia classify islet allotransplantation as therapeutic and not experimental at this time.
The waiting list as of January 1, 2014, divides the pancreas waiting list into two sections: pancreas alone (1,178 patients) and kidney/pancreas listing (2,031 patients) (Table 1).
The first intestine transplant was by Dr. Thomas Starzl in 1987 on 3-year-old Tabitha Foster.14 Tabitha had been born with short-gut syndrome and had never eaten solid food. Although she only needed intestines and a liver, the surgeons found it easier to transplant the large intestines, stomach, and pancreas along with the small intestine. A splenectomy was also done at the same time. However, Tabitha died 6 months later of Epstein-Barr virus.40
Intestinal transplants are the rarest of organ transplants, with only 46 patients on the transplant list as of January 1, 2014.2 The most common reason for an intestinal transplant is short-gut syndrome followed by functional bowel problems such as Hirschsprung syndrome.41 An intestine transplant can be combined with a liver transplant. Priority for intestine transplants uses the same scoring system as for livers.20
The first corneal transplant was performed in 1905 by Eduard Zirm on a farm worker who had burned both eyes while cleaning a chicken coop. A living donor was used, an 11-year-old child who was blind in one eye due to a penetrating injury in the past. The donor eye was enucleated and the cornea was cut into two sections and implanted into the recipient's eyes. Only one of the corneal transplants survived and the farm laborer had some vision in one eye.42 As living donors are uncommon, the concept of deceased donor corneas was broached, and the first eye bank was opened in 1944. Surgical techniques were refined and rejection was controlled. Forty thousand corneal transplants are performed in the United States each year.
The leading causes of blindness are cataract, glaucoma, and corneal opacity. Corneal blindness has many causes, ranging from infections to genetic causes. Corneal grafting is used to treat corneal opacity, although lamellar techniques (which remove just the diseased layers of the cornea) are becoming more frequent.43 Lamellar techniques can use full-thickness or partial-thickness corneal grafting (keratoplasty) and have an excellent record of success (80% to 90%).44
Challenges to corneal transplant remain, including a lack of donors. In 2008, the Eye Bank Association of America estimated that about 92,000 corneas were recovered. Of these only 33% were suitable for transplantation. Great strides are being made in developing other techniques to respond to the lack of donors.45 About 20% of patients who undergo keratoplasty reject the implanted corneas, despite antirejection drugs. However, due to advances in cornea transplant and surgical techniques, corneal transplants have allowed many to see who would otherwise remain blind.45
Transplant medication protocols have gone through a sea change over the years. Steroid-driven protocols, which were often the cause of new-onset diabetes, are rare now in the United States.13 Besides induction protocols, most immunosuppressive therapy regimens include a calcineurin inhibitor such as cyclosporine or tacrolimus, and an antimetabolite such as azathioprine, mycophenolate mofetil, sirolimus, or everolimus.13 Each transplant center and each organ has its preferred posttransplant protocol, and a discussion of transplant medications is beyond the scope of this article. However, many PAs will see posttransplant patients in their offices and hospitals, and must remember that:
- transplant patients should not be given live vaccines
- skin cancer is the most common posttransplant complication; squamous cell cancer is more common than basal cell cancer
- all transplant medications have a narrow therapeutic and toxic window, and any interference with the cytochrome P450 system will affect metabolism. Calcium channel blockers, IV protease inhibitors, azole antifungals, antiarrhythmics, antibiotics, antidepressants, antiepileptics, and grapefruit juice can interfere with the cytochrome P450 system and transiently increase or decrease levels of antirejection medications.
PAs who practice in an area without a close transplant center may handle a significant amount of primary care for transplant patients, and should be familiar with the transplant center's protocols. Remember that all transplant patients have chronic kidney disease, no matter which organ was transplanted, because transplant medications affect kidney function.46 All medications should be dosed according to the patient's estimated glomerular filtration rate and not the practice's standing protocols.
The main obstacle to transplant is a lack of donors and not a lack of recipients. In fact, the rate of deceased donors has been flat for 6 years, and the living donor rate has dropped recently (Figure 7). The longest waiting times are for kidneys—8 years or longer in some areas of the country. Part of this is due to the increase in kidney failure, but a second factor is the increased survival of patients with end-stage renal disease, thanks to improved dialysis and better medical management. Studies have shown that minority patients are less likely than nonminority patients to be on a kidney transplant list before starting dialysis.47 Although some of this discrepancy is insurance-driven, the new donation protocols attempt to level the playing field by backdating waiting time to start on the first day of dialysis.7
Two main drives—living donation and presumed consent—have sought to increase donation rates. Living donation is only feasible for kidney, liver, and some lung transplants. However, many of the causes of kidney failure run in families, and the lack of available living donors caused the living donation rate for kidneys to drop in 2012. First-person consent states that if an appropriate deceased donor dies while admitted to a hospital or is dead on arrival, until stated otherwise, the patient will receive care to save the organs for eventual transplant. This also means that if patients have indicated on their driver's licenses that they are organ donors, family permission is not needed to recover the organs. All 50 states and the District of Columbia have a link between the license donor registration and the organ procurement organizations to allow access of first-person consent in case of death.48
Social media has opened a new outlet for a discussion of living donor transplant.49 Although buying or selling organs is illegal, Facebook recently added a donation button to its social media outreach.50 Various online programs attempt to match patients with organs. Social media outreach remains controversial because of the fear of exploitation, given the high demand for donor organs.
One of the most interesting concepts to emerge is a marketing-type outreach recently reported from the United Kingdom (UK).49 Despite the addition of more than 1 million people to the UK donor list in 2011, the donor shortage means that three patients die every day while waiting for a transplant. The UK's Behavioural Insights Team partnered with the National Health Service and the Driving and Vehicle Licensing Agency to undertake a randomized controlled study to increase donor registrations. When UK drivers went online to renew their license, a screen with one of seven scenarios for donor signup would appear:
- the standard request for donation
- a “social norm” message (“Every day, millions of people ...”) with a photo of a patient
- a “social norm” message without a patient photo
- a “loss” message (“Three people die each day...”)
- a “gain” message (”You could save up to 9 lives...”)
- a fairness message (“If you needed an organ transplant, would you have one? If so, please help others”)
- No message.
The scenario that increased the signup rate was the fairness message. Interestingly, the message with the photo of a patient in need reduced the signup rate. This has changed marketing plans in the UK and should be adopted in the United States.
Due to the shortage of donor organs, many researchers hope to develop artificial organs. Nonhuman animal cells have been used to treat human conditions (xenotransplant) since the early days of transplant. Although xenotransplantation is common in heart valves, it is not yet used in solid organ transplant.51 Recent advances in 3D printing in biotechnology are showing very interesting results.52 The ability to grow a kidney on a matrix also holds promise for future directions in research.53
Transplants are becoming commonplace and more transplant recipients will be seen in primary care offices. PAs need to have a working knowledge of the types of transplants and general protocols. Patients may mention in passing that a friend, colleague, or neighbor may need a transplant. This can lead to a discussion of donation and the desperate need for more organs. PAs are perfectly placed to dispel rumors and misconceptions about transplants and organ donation.
Every day, 17 patients die waiting for a transplant. Each donor saves seven to eight lives, depending on if the liver is split. However, fewer than half of potential donor families are even asked about donation. By understanding organ donation and educating patients, PAs can help fulfill the saying, “To the world you may be one person, but to one person you may be the world.”
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Keywords:© 2014 American Academy of Physician Assistants.
transplant; living donation; deceased donor; organ; extended criteria; xenotransplantation