By Miguel Tan, M.D., MSc, FRCSC and Joshua Wolf, M.D.
From ATLANTA Medicine, 2013, Transplantation, Vol. 84, No. 1
Despite significant advances in kidney transplantation outcomes over the last decade, the number of transplants performed remains constrained by the limited number of available kidney donors. Nationally, the number of deceased kidney donors has stagnated while the recipient waiting list continues to grow. The Scientific Registry of Transplant Recipients (SRTR) data shows that the number of donors peaked in 2006- 2007(1) and has either reached a steady state or declined in subsequent years.
In Georgia alone, the number of deceased donors declined by approximately six percent from 2009-2010 to 2010-2011. The exact reason for this is not well known, however, the increasing age and obesity of the general population has lead to more marginal donors with poor-quality organs that end up being unusable. The number of new patient registrations, on the other hand, continues to grow at two percent to three percent a year. Four percent to five percent of potential recipients die on the waiting list.(2) Nationally, 4,500 people a year die while waiting for a kidney transplant. Currently, the average waiting time for a deceased donor kidney in Georgia is four to five years.
Living kidney donation has improved outcomes and access to transplantation by decreasing waiting time, improving long-term outcomes and allowing recipients on the deceased waiting list to “move up” in the queue by decreasing the number of recipients who would otherwise be in the “pool” awaiting a deceased donor organ. The five-year graft survival of a living donor kidney is 82.9 percent compared to 70.6 percent for a deceased donor(2). The additional benefit of this improved long-term outcome is that it reduces the number of recipients that may require re-transplantation at a future date due to the almost double half-life of a live donor kidney compared to a deceased donor organ.
Paired Kidney Exchange
Although the importance of living donation is well established, it is estimated that only a third to half of potential living donors and their intended recipients are compatible. A larger number have medically suitable and willing donors, but cannot donate to their intended recipient due to either blood type mismatch or recipient antibodies to the donor.
Paired kidney exchange addresses this imbalance by entering incompatible donor/recipient pairs into a database that allows us to identify other incompatible pairs and ‘swap’ donors to achieve compatible kidney transplantation.
A variant of paired kidney exchange is the so-called domino chain transplant. This is made possible by an “altruistic” or non-directed donor who is prepared to donate a kidney to anyone in need. When this type of donor is entered in a paired exchange registry, it can result in a cascade effect or “chain” of transplants.
The main advantage of chain donation is eliminating the need to perform all the transplants simultaneously, as described in a “standard” paired exchange. This significantly eases the resource and logistic burden on the hospital, surgeons and patients. In addition, using a “bridge” donor allows for potential continuation of the chain as long as suitable pairs are subsequently found. One of the longest current chains was completed last year and involved 17 hospitals in 11 states, resulting in 30 kidney transplants as a result of the generosity of one non-directed donor(3).
For example, one nine-pair chain ended with the final donor held as a ‘bridge’ donor in order to initiate the another chain. This particular example illustrates the first reported intercontinental kidney domino exchange in the world that our center participated in. The generosity of one altruistic donor led to nine kidney transplants that otherwise would not have happened. The bridge donor at the end of this segment will allow the chain to continue.
Previous data(4) based on mathematical simulations has suggested that efficient use of these “domino” chains would result in 1.9 to 3.8 transplants per chain. However, a more recent retrospective study(5) shows that the benefit is potentially much greater. A multicenter study involving 272 kidney transplants actually yielded an average of five transplants per chain. This data illustrates the importance of altruistic/non-directed live kidney donors in increasing the number and quality of kidney transplants.
In the past, these endeavors were performed using “in-house” or regional programs limiting the potential pool. However, the importance of paired exchange has reached a point that a National Paired Kidney Donation Pilot Program was formed to maximize the opportunity for patients to receive a living donor kidney who otherwise would not have access to living kidney donation. Paired exchange essentially did not exist in 2000. By 2008, almost 300 such exchanges were performed annually.
Current projections estimate that a well- utilized national network can increase the number of kidney transplants by 10 percent to 15 percent – no small feat considering that there are more than 91,000 patients awaiting kidney transplantation in the United States. There are more than 3,200 patients waiting for kidneys in Georgia alone.
Because living kidney donation is an altruistic act, donor safety is of paramount importance to the transplant community. In most programs, diabetes, obesity (BMI >30-32 kg/m2) and hypertension are contraindications to donation. Properly selected donors, however, have excellent long-term outcomes. A number of studies support the long-term safety of kidney donation, including a large study by Ibrahim et al(6). From 1963-2007, 3,698 living kidney donors were evaluated and demonstrated that carefully screened donors had the same survival and risk of end-stage renal disease as controls who were matched for age, sex and race. They also had preserved GFR, normal albumin secretion and a good quality of life.
Improving Surgical Safety and Donor Recovery
The advent of laparoscopic surgery was a boon to living kidney donation by greatly improving post-operative pain, recovery and cosmetic outcome. What used to entail an open procedure requiring a large flank incision with rib resection is now performed through two or three half-inch incisions and a three-inch incision to remove the kidney with relatively little post-operative pain. The patient typically remains in hospital for one to two days and has a rapid return to normal function.
Compared to open surgery, however, the margin of safety with laparoscopy is narrower due to the loss of 3-D visualization when observing a flat television monitor during surgery as well as instrumentation limitations. This limitation has been abrogated somewhat by robotic surgical techniques that utilize 3-D technology. The advantages of robotic technique include better visualization of fine structures in limited spaces and improved articulation of robotic instruments compared to the standard laparoscopic approach. While still a technique limited to more advanced transplant centers, its use is gaining ground as more surgeons become proficient in robotic applications.
End-stage renal disease remains a significant health issue. Kidney transplantation is the gold standard for treatment for most causes of ESRD. In order to address the shortfall in available organs, living donor and paired exchange transplantation has been developed. As an added benefit, live donor kidneys offer superior long-term outcomes compared to deceased donor organs, while paired exchange programs allow incompatible pairs to participate in and receive live donor organs.
Achieving higher kidney transplant rates not only benefits recipients through improvement mortality and quality of life, but provides significant cost savings to the healthcare system as a whole. Previous meta-analysis have demonstrated that maintaining a patient on dialysis costs more than $300,000 per Quality Adjusted Life Year (QALY). Living donor kidney transplantation reduces that cost to $120,000 per QALY(8).
In addition, advances in surgical technique has led to significant improvements in donor outcomes, thus removing most of the risk and morbidity associated with the earlier era of open-donor nephrectomy.
1. SRTR annual report, www.srtr.org
3. Sack, K. 60 Kidneys, 30 Lives, All Linked. New York Times, 2012, February 19. p. A1
4. Gentry SE, et al. Am J Transplant 2009; 9: 1330-1336
5. Melcher ML, et al Am J Transplant 2012, 12:2429-2436
6. Ibrahim, H NEJM 2009; 360(5):459-69
7. Tan, M ed. A Brief Guide to Abdominal Organ Transplantation: Practical Management of the Peri-Operative Transplant Patient. 2011, P.89
8. Demartines N, Schiesser M, Clavien PA. An evidence-based analysis of simultaneous pancreas-kidney and pancreas transplantation alone Am J Transplant. 2005 Nov;5(11):2688-97
Miguel Tan, M.D., MSc, FRCSC, is a multi-organ transplant surgeon and serves as surgical director of kidney and pancreas transplantation at Piedmont Transplant Institute. Previously, he was Assistant Professor of Surgery in the Division of Transplantation at Johns Hopkins Hospital in Baltimore, Md. He received his medical degree and completed his residency at McGill University in Montreal. Dr. Tan completed a clinical fellowship in transplant surgery at the University of Minnesota.
Joshua Wolf, M.D., is a transplant nephrologist at the Piedmont Transplant Institute in Atlanta. Dr. Wolf has special interests in living donor transplantation as well as transplanting the highly sensitized recipient. He is board certified in Internal Medicine and Nephrology by the American Board of Internal Medicine. He received his undergraduate and medical degree from Emory University School of Medicine, completed his internship and residency at New York University Medical Center, and completed his general and transplant nephrology training at the University of California, San Francisco.