Figure 1: Simultaneous pancreas-kidney transplantation has unique advantages for patients with end-stage renal disease.
The Penn Transplant Institute offers simultaneous pancreas/kidney (SPK) transplantation, a procedure with the potential to improve both kidney graft and patient survival in comparison to kidney transplantation alone.
At Penn, SPK is offered to insulin-dependent diabetic patients age 60 and under with end stage renal disease (ESRD), typically as a consequence of diabetes mellitus, the leading cause of kidney failure. About 85% of pancreas transplants in the United States occur as SPKs. While the majority of these procedures occur in type 1 diabetics, type 2 diabetics accounted for 23% of SPKs performed in the US in 2020. [1]
SPK offers unique advantages to patients with diabetic ESRD, whose treatment options are limited to kidney transplantation alone or peritoneal dialysis or hemodialysis. Kidney transplantation is an ideal approach, but the median wait time for a good quality deceased donor kidney in the United States is now 3.6 years (5-8 years in the Mid-Atlantic region). Most patients anticipating a kidney transplant will undergo dialysis as a bridge to transplant. Dialysis is associated with significant mortality rates, however, and carries many additional risks and complications for the diabetic population. Generally, diabetic patients on dialysis have a life expectancy of 3 to 5 years.
Survival Rates: SPK vs. Kidney Transplantation Alone
Kidney transplantation, alone or in combination with a pancreas, is the only approach that can preempt or minimize dialysis exposure for patients with end-stage kidney failure. However, kidney transplantation with continued insulin therapy does not resolve the condition that caused kidney failure in the first place.
To achieve this end, experienced transplantation centers, including the Penn Transplant Institute, have been transplanting a pancreas either at the time of kidney transplant (e.g., SPK), or following kidney transplantation alone (pancreas after kidney transplantation, or PAK). Five-year survival rates for kidney transplantation from deceased donors is approximately 86% (93% for living donor transplants). By comparison, the national patient survival rate for SPK at five years post transplant is 92.7%. [1]
SPK is more widely used than PAK because most patients do not have a living donor. The attendant advantages of SPK vs PAK include the relative benefits of a single procedure versus multiple surgeries, and an immunologic benefit for the pancreas in that the kidney from the same donor can signal early rejection of the pancreas, conferring increased long term pancreas graft survival compared to PAK.
Recent changes in organ allocation may also have benefits for SPK. With reference to SPK, the process of organ allocation shifted in December 2014, when the United Network for Organ Sharing (UNOS) launched a new system to disentangle the pancreas and kidney waitlists and enhance the possibility that both organs can be allocated to candidates for SPK transplant. This has utility not only for timing (the waiting list for a pancreas is much shorter than that for a kidney) but for improved kidney quality, since the risk factors that impact kidney quality are typically absent among pancreas donors.
Outcomes Data
- In 2020 there were 19,458 living recipients of pancreas transplants in the US.[1]
- The National patient survival rate for SPKs is 97.14% at one year, 92.7% at five years, and 79.1% at 10 years post transplant. [1]
- The rate of kidney graft function (as part of the SPK transplant) is 95.8% at one year and 66.6% at 10 years. [1]
- Nationally, the rate of pancreas graft function at one year for SPK is 93%.[1]
- Long term graft survival is excellent for SPK transplantation; the point in time when 50% of grafts are lost/still functioning is >15 years (for both the pancreas and the kidney). [1]
- In a large nationwide cohort study performed in the Netherlands in 2020 that compared SPK to kidney transplantation alone, SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest rate of survival (median 17.4 years). [3]
- The rejection rate for SPK is lower (10.6%) compared to PAK (12.5%) and PTA (21.8%). [1]
- While the average wait for a simultaneous kidney and pancreas transplant varies by blood type and area of the country, the median wait time for SPK in the Mid-Atlantic region is between 1 and 3.5 years.
References
- Kandaswamy R, Stock PG, Miller J, et al. OPTN/SRTR 2020 Annual Data Report: Pancreas. Available at: https://srtr.transplant.hrsa.gov/annual_reports/2020/Pancreas.aspx.
- Montori VM. Basu A. Erwin PJ. Velosa JA. Gabriel SE. Kudva YC. Posttransplantation diabetes: a systematic review of the literature. Diabetes Care. 2002;25:583 – 592.
- Esmeijer K, Hoogeveen EK, van den Boog PJM, et al. Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort. Diabetes Care 2020;43:321-328.
SPK at the Penn Transplant Institute
Dr. Ty Dunn has a rare insight into the lives of individuals with end-stage kidney disease and diabetes, and the needs that bring them to the Penn Transplant Institute, one of the nation's leading transplant centers. A transplant surgeon whose career has focused upon both individual and multi-organ transplantation, Dr. Dunn is the Surgical Director of Kidney and Pancreas Transplantation at the Penn Transplant Institute.
"The Penn Transplant Institute is exceptional for its concern for the long-term well-being of patients, and the experience and skill of our team," Dr. Dunn said one afternoon in late March. "What this means is that we have the expertise to be both aggressive in pursuit of the best quality organs, and to manage potential complications should they arise."
As shown in Figure 1, kidney and/or pancreas transplantation typically does not involve removing the native organs (unlike heart, lung and liver transplant). In the instance of SPK, the donated kidney is placed in the lower abdomen, to the right or left of the bladder to which it is attached by its ureter; it receives blood flow from the nearest iliac artery and vein. The pancreas is typically transplanted on the right side with a segment of duodenum anastomosed to the recipient's jejunum and receives its blood flow from the common iliac artery; the venous outflow can be systemic (from the inferior vena cava or common iliac vein), or portal (superior mesenteric vein).
Case Study: A Patient with Advanced Diabetes-Induced Kidney Failure
In a recent interview, Dr. Dunn described a patient with advanced kidney disease seeking a kidney transplant for biopsy-proven diabetic nephropathy.
"Bill came to us at age 48 with stage 4 chronic kidney disease," Dr. Dunn said. "He'd had type 2 diabetes for 23 years, requiring insulin for 10 of those years."
Among other concerns, Bill's looming kidney failure meant he would soon have to begin dialysis. Despite efforts to care for himself, his many complications (in addition to end-stage renal failure) included diabetic retinopathy, cataracts, and peripheral neuropathy. His GFR at presentation was 23 (normal range 100 – 130); his A1C was 7.9; his blood was type A.
During evaluation, Dr. Dunn and her team assessed Bill to better understand his circumstances and burden of disease, his health literacy, and his ability to understand the risks and benefits of his transplant options. The purpose of these efforts was to help him make an informed decision about his future to ensure that the decision for transplant was in concordance with his wishes.
At the Penn Transplant Institute, Dr. Dunn explained, Bill's options would include simultaneous pancreas/kidney transplantation, a living or deceased donor kidney transplant, with the option of a pancreas after kidney transplantation (PAK). However, like so much else for individuals with diabetic kidney disease, Bill's future depended upon other findings from his transplant evaluation, including cardiac status, vascular disease, hypercoagulability, and any other as yet undisclosed issues he might have.
Options, Stratagems, and Advantages
Bill now entered an interim defined by time dependencies, opportunity, risk, strategy, design, and occasionally, luck. Whether or not he achieved his ultimate objective — freedom from dialysis and insulin — could depend upon decisions made in the initial stages of his journey. One critical early consideration is the need to avoid dialysis and its many adverse effects.
"For patients at risk for kidney failure, it's important to avoid or minimize dialysis time by finding the most direct path to a kidney transplant, preferably in combination with a pancreas, or from a living donor, if one is available," Dr. Dunn says. But in the next few weeks, all of Bill's potential living donors proved to have disqualifying physiological issues, making SPK an increasingly attractive option to achieve his goals.
SPK: An Option for Patients Seeking Kidney Transplantation
"Because pancreas donors are younger and fitter, the quality of a kidney from a deceased pancreas donor is often as good as — or sometimes better than — that from a living donor," Dr. Dunn says, adding that a successful pancreas transplant as part of an SPK protects against the recurrence of diabetic nephropathy, and can slow or prevent the other complications of diabetes.
Dr. Dunn advised Bill to get on the waiting list for a pancreas and kidney, although he was technically ineligible to accrue waiting time for the latter as his GFR was still above 20ml/min.
"The UNOS qualifying time (date from which waiting time can accrue) for a kidney can't begin until the GFR is 20 or below, but for pancreas wait time, accrual begins on the date of listing," she explains. "By getting on the waiting list for an SPK, patients will accrue pancreas waiting time, which is important in case they are able to achieve a living donor kidney, at which time the SPK waiting time converts seamlessly to their pancreas waiting time for PAK."
Bill was fortunate in that his clinical situation favored SPK. Despite the hardships of diabetes and struggling with hypoglycemic unawareness, he was genuinely motivated to be insulin free, had demonstrated compliance with his medical regimens, and expressed a willingness to take on additional surgical risk (over kidney alone transplantation) to gain freedom from diabetes. Furthermore, he was young and relatively lean (BMI 28), both ideal characteristics for an SPK candidate.
Bill was placed on the waiting list for a pancreas, and when his GFR dipped below 20 (as monitored by the transplant center), he began accruing kidney waiting time as well. A year later, when his GFR approached 14 and he was becoming symptomatic from his kidney failure, he started to receive organ offers.
"The urgency for a transplant recipient approaching dialysis is to get an organ, and soon," Dr. Dunn says. "But what's needed isn't just any organ, but the best organ we can find."
Soon thereafter, Dr. Dunn was notified about a potential organ donor with favorable characteristics for donation of a pancreas and a kidney.
"The donor was 27 years old with a BMI of 23; he had an A1C of 5.2 and a creatinine of 0.8," she said. "In the operating room, the pancreas and kidneys appeared completely normal." A virtual crossmatch confirmed that the donor and Bill were compatible.
SPK Surgery - A Third Kidney, A Second Pancreas
Bill was admitted to the Hospital of the University of Pennsylvania, to which the organs were transported soon afterward. At the hospital, he had his COVID test, labs, EKG, and chest x-ray, and awaited organ arrival.
While Bill was undergoing anesthesia, the transplant team was preparing the organs for transplantation, which takes between one and two hours to complete. As this process neared its completion, part of the team began the operation on Bill with a midline incision to inspect the internal organs and the vasculature, to determine where the kidney and pancreas would be implanted.
"Our practice is to put the kidney in first — this doesn't take long, and can usually be accomplished while the pancreas is being prepared," Dr. Dunn explains. "This minimizes cold time and also helps us manage potassium for patients that are on dialysis — and then we put the pancreas in. If extended cold time is a concern, we may choose to anastomose the pancreas first."
Bill's surgery went well, and at its conclusion, he was moved to the intensive care unit and monitored for one day for bleeding, clotting, and function of his newly transplanted organs. By his second day, Bill was ambulatory and after a few days when it was evident that his GI system was returning to normal function, his diet was advanced, with careful attention to maintenance of hydration.
Although historically 50% of SPK patients are readmitted in the first year as a result of complications related to longstanding diabetes (e.g., dehydration, nausea, gastroparesis, constipation), Bill was not among them.
"Our goal is to keep our patients safe during recovery," says Dr. Dunn. "The first three months are the busiest — we follow them pretty intensively for the first month in the clinic — they're in the clinic every week. They get labs twice a week for a couple of months, and once things settle out and they're successful, they're destined to do well for a long time. In the long-term, we watch for the development of complications related to their history of longstanding diabetes, or immunosuppression-related side effects. Patients having SPK have the lowest risk of pancreas rejection, which is good because this correlates with lower levels of immunosuppression and increased pancreas longevity, in contrast to PAK or PTA transplant recipients."
Bill's recovery was uneventful, and at one year, his pancreas and kidney grafts show no signs of rejection, and his glycemic control was excellent.
For more information about pancreas and kidney transplantation at the Penn Transplant Institute, please call 215-662-6200.
About the Penn Transplant Institute Pancreas Transplant Program
The Penn Transplant Institute pancreas transplant program was the first program in the region to offer pancreas transplant as treatment for type 1 diabetes, and is one of the leading transplant centers in the world researching islet cell transplantation. As a member of the Clinical Islet Transplantation Consortium funded by the National Institutes of Health, we participate in clinical trials for islet transplantation in addition to clinical trials studying aspects of pancreas transplantation.
Performing SPK Transplantation at the Penn Transplant Institute
Pancreas Transplant Surgeons: