Daniel M. Keller, PhD

October 16, 2012

October 16, 2012 (Berlin, Germany) — Simultaneous pancreas-kidney (SPK) transplantation provides better long-term patient survival compared with single kidney transplantation alone for patients with type 1 diabetes (T1DM) and end-stage renal disease (ESRD). Speaking at the European Association for the Study of Diabetes (EASD) 48th Annual Meeting, Trond Jenssen, MD, PhD, from Oslo University Hospital, Rikshospitalet, in Norway, said that the advantage of SPK transplantation over live kidney donation statistically depends on donor age.

Various studies have supported superior survival with either SPK transplantation or live kidney transplantation alone. The inconsistent results may be from a combination of factors, including differences in age and comorbidities, immunosuppressive regimens, and surgical techniques, as well as small sample sizes or short follow-up times.

Oslo University Hospital is the national center for solid organ transplantation in Norway. In the period from January 1983 to December 2010, 5885 patients with ESRD underwent renal transplantation there, of whom 630 had ESRD from diabetic nephropathy. All patients who undergo transplantation are in a national registry and can be followed up yearly for medical information.

Patients were generally offered SPK if they were fit enough and younger than 50 to 55 years. But to minimize time on dialysis, patients who had a live kidney donor usually received a single live kidney transplant. Older patients or those with comorbidities generally received a single deceased donor kidney because of the increased operative risk with SPK.

Using the registry, Dr. Jenssen and colleagues addressed the question of whether survival is improved by SPK transplantation compared with single kidney transplantation in T1DM patients with ESRD. Of the 630 patients in this cohort, 171 were transplanted with a live donor single kidney, 222 were transplanted with SPK, and 237 received a deceased donor single kidney.

All patients received immunosuppression with prednisolone 5 mg/day and either cyclosporine or tacrolimus. Before the year 2000, they received azathioprine; after the year 2000, patients received mycophenolate. Similarly, after the year 2000, patients received induction therapy with basiliximab for single kidney transplants or thymoglobulin when a pancreas was transplanted.

Surgical techniques for pancreas transplantation also changed over the years, with neoprene occlusion of the pancreatic duct up until 1988, followed by pancretico-vesical (bladder) anastomosis up to 1999, and then pancreatico-enteral (intestinal) anastomosis from 2000 to the present.

Five- and 10-year pancreas graft survival more than tripled from 1983 to 2010. Ten-year graft survival was about 20% from 1983 to 1987, just under 50% from 1988 to 1999, and about 65% from 2000 to 2010.

Patient characteristics differed somewhat depending on the kind of transplants they received. SPK recipients as a group were younger (41 years) than living donor kidney recipients (45 years) or deceased donor kidney recipients (55 years). SPK donors were younger (30 years) than living kidney donors (50 years) or deceased kidney donors (46 years). Cold ischemia time was shortest for living donor kidneys (3 hours) compared with SPK organs (11 hours) or deceased donor kidneys (15 hours). Human leukocyte antigen-D related (HLA-DR) matches were greatest for deceased donor kidneys (46%), followed by living donor kidneys (36%), and least for SPK (22%).

Fifteen-year patient survival was greatest for SPK recipients, at about 49%, followed by living donor kidney recipients, at about 30%, and about 12% for deceased donor kidney recipients (figures were estimated from Kaplan-Meier curves).

Dr. Jenssen calculated a hazard ratio (HR) for patient death using multivariate models correcting for significant risk factors, using living donor kidney recipients as the reference. Adjusting for recipient age, time on dialysis, and transplant era, SPK recipients were at a statistically significantly 30% lower risk for death vs living donor kidney patients (HR = .70; 95% confidence interval [CI], 0.52 - 0.95; P = .02).

When adjustments were made for donor age in addition to recipient age, time on dialysis, and transplant era, the risk for death for SPK recipients was statistically no different from the risk for living donor kidney recipients (HR = .84; 95% CI, 0.68 - 1.18; P = .32). However, deceased donor kidney recipients were at a greater risk for death (HR = 1.41; 95% CI, 1.04 - 1.93; P = .029).

Among the 317 patients who died, the causes of death were mainly cardiovascular (59%). Infections accounted for 15% of deaths, malignancy for 8%, and other causes for 18%.

Survival Rates Depend on Donor Age

In summary, Dr. Jenssen told the delegates that SPK transplantation is superior to single kidney transplantation in terms of long-term patient survival. "However, the advantage over live kidney donation is statistically dependent on donor age," he said. He added that survival of pancreas grafts has improved over the past decade.

He concluded that patient survival is best in T1DM with ESRD when kidney transplantation is combined with a pancreas graft. In response to a question from the audience about the possible effect of better glycemic control in patients who received a pancreas, Dr. Jenssen said that he had not included that variable in his multivariate model but that it was a good point and that it would be possible to address that question for patients transplanted after the year 2000 because glycated hemoglobin values should be available.

Session moderator Ezio Bonifacio, PhD, professor of diabetes preclinical stem cell therapies in the Center for Regenerative Therapies at the Technische University in Dresden, Germany, commented to Medscape Medical News that Dr. Jenssen presented a very good clinical study based on a registry from a single center.

"It knows exactly what's being done, it's very well documented, the numbers are...good," he said. "It says that [SPK patients] do at least as well as a living kidney alone."

The study adds support to the idea that "a simultaneous kidney-pancreas transplant is good. This study doesn't change our opinion," Dr. Bonifacio, who was not involved in the study, said.

Some patients received a living kidney donation and were later transplanted with a deceased donor pancreas. Dr. Bonifacio questioned whether it would be wise to risk losing the kidney if the patient was challenged with more alloantigens from the pancreas. But he said it was really up to the patient to weigh the benefit of getting the pancreas transplant.

Dr. Jenssen and Dr. Bonifacio have disclosed no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 48th Annual Meeting: Abstract 149. Presented October 4, 2012.

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