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Superior Long-Term Survival for Simultaneous Pancreas–Kidney

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Superior Long-Term Survival for Simultaneous Pancreas–Kidney Diabetes Care 1 Kevin Esmeijer,1 Ellen K. Hoogeveen,1,2 Superior Long-Term Survival for Paul J.M. van den Boog,1 Cynthia Konijn,3 CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL – Marko J.K. Mallat,1 Andre G. Baranski,4 Simultaneous Pancreas Kidney Olaf M. Dekkers,2,5 and Johan W. de Fijter,1 Transplantation as Renal on behalf of the Dutch Transplant Centers Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort https://doi.org/10.2337/dc19-1580 OBJECTIVE In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas–kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. RESEARCH DESIGN AND METHODS We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored 1Department of Nephrology, Leiden University (30% SPK). Medical Center, Leiden, the Netherlands 2Department of Clinical Epidemiology, Leiden RESULTS University Medical Center, Leiden, the Nether- Of 996 transplanted patients, 42%, 16%, and 42% received a deceased or living- lands 3Netherlands Organ Transplantation Registry, donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was Leiden, the Netherlands 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 4Department of Surgery, Leiden University Med- (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients ical Center, Leiden, the Netherlands 5 with a functioning pancreas graft at 1 year (91%) had the highest survival (median Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted Corresponding author: Kevin Esmeijer, k.esmeijer@ hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) lumc.nl and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; Received 7 August 2019 and accepted 3 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney November 2019 transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; This article contains Supplementary Data online 0.78) and 0.69 (0.52; 0.90), respectively. at http://care.diabetesjournals.org/lookup/suppl/ doi:10.2337/dc19-1580/-/DC1. CONCLUSIONS © 2019 by the American Diabetes Association. Compared with living- or deceased-donor kidney transplantation, SPK transplant Readers may use this article as long as the work is was associated with improved patient survival, especially in recipients with a long- properly cited, the use is educational and not for profit, and the work is not altered. More infor- term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mation is available at http://www.diabetesjournals mortality rate. .org/content/license. Diabetes Care Publish Ahead of Print, published online December 4, 2019 2 Pancreas–Kidney Transplant as Renal Therapy Diabetes Care The global population with type 1 di- functioning pancreas graft had a supe- the registries. Organs were allocated ac- abetes approaches 40 million. Approxi- rior 7-year survival as compared with cording to the standard Eurotransplant mately 78,000 children are diagnosed patients with type 1 diabetes with a guidelines. Because patients with type 1 with type 1 diabetes annually, and the living-donor kidney transplant (89% vs. diabetesondialysishaveapoorprognosis, incidence is expected to rise by 3% per 80%). Eurotransplant applies mandatory ex- year (1). Micro- and macrovascular dam- Taken together, there is no consensus change rules for SPK transplants to pri- age due to impaired glucose regulation on whether SPK compared with kidney oritize this patient category in case of a leads to diabetic retinopathy, nephrop- transplantation alone actually improves potential SPK donor. These rules explain athy, neuropathy, and angiopathy and a mortality risk in patients with type 1 the shorter waiting time for SPK as com- threefold increased mortality risk as diabetes, especially in the long term. pared with kidney transplantation alone, compared with individuals without di- Therefore, we investigated the effect as well asthe relatively largeproportionof abetes (2). As such, type 1 diabetes is of SPK in comparison with kidney trans- pre-emptive SPK transplant procedures accompanied by considerable health plantation alone, either from a living or (36%) (13). Deceased-donor kidney and care costs, estimated at ;10,000 US deceased donor, on long-term survival SPKtransplantswereperformedfollowing dollars per patient per year (3). in a nationwide cohort including all Dutch donation after brain death procedures in Patients with type 1 diabetes have a patients with type 1 diabetes who have 95% of cases. high cumulative risk of 7% to develop required renal replacement therapy in end-stage renal disease requiring renal the past 30 years. Regional Differences in Treatment replacement therapy within 30 years (4). Strategy Compared with dialysis, kidney trans- RESEARCH DESIGN AND METHODS The postal code of the patient with type 1 plant recipients have a substantially im- Study Population diabetes strictly determines treatment proved survival and quality of life (5,6). In We included consecutive (n 5 2,833) in a defined dialysis center, and each contrast to a kidney transplant alone, patients with type 1 diabetes aged at dialysis center is affiliated with a specific a simultaneous pancreas–kidney (SPK) least 18 years, who started on chronic transplant center. Since the first pan- transplantation may also restore endog- dialysis or received a first kidney trans- creas transplant in the Netherlands in enous insulin production and, at least plant in the Netherlands between 1 Jan- 1984, the Dutch Ministry of Health con- partially, reverses progression of diabetic uary 1986 and 1 January 2016. We sidered SPK transplantation an experi- micro- and macrovascular complications excluded patients who received a pan- mental and restricted procedure. The (7). Controversy remains, however, as to creas transplantation alone (n 5 17) or a results have been that the vast majority whether an SPK compared with a kidney pancreas after kidney transplantation of the SPK transplants have been per- transplant alone improves patient sur- (n 5 20); thus, 2,796 patients were formed in Leiden, which is only one of vival. Specifically, it is unknown whether eligible for the present analysis. In total, eight Dutch transplant centers. These an SPK should be preferred over a living- 1,800 patients were on chronic dialysis policies created regional differences in donor kidney transplant. only, and 414, 161, and 421 patients the assignment of SPK transplantation to For practical or ethical reasons, no received a deceased- or living-donor kid- patients with type 1 diabetes, in essence randomized clinical trials have compared ney or SPK, respectively (Supplementary largely based on their place of residence. survival after SPK versus kidney trans- Fig. 1). Weused data from two mandatory We therefore defined two transplant plantation alone. We previously showed, nationwide Dutch registries. The Nether- areas: the Leiden area, with an average in Dutch patients with type 1 diabe- lands Organ Transplant Registry includes population of 2.5 million inhabitants tes between 1985 and 1996, that patients who received a kidney transplant during the 30-year follow-up period, a treatment strategy favoring SPK over from all eight Dutch kidney transplant and the rest of the Netherlands, with a deceased-donor kidney transplant centers, containing information on donor 14.0 million inhabitants. In the Leiden alone was associated with a 47% lower and recipient characteristics as well as area, consisting of one transplantation 10-year mortality risk (8). In a US registry outcome parameters. The registry com- center, the primary intention is to treat study among 18,549 patients with type 1 bines the donor, procurement, and allo- patients with type 1 diabetes with end- diabetes during 1987–1996, 8-year sur- cation data from the Eurotransplant stage renal disease with an SPK trans- vival after SPK or a living-donor kidney Network Information System with trans- plant.Thus, SPKtransplantwasofferedto transplant was similar at 72% and better plant center-specific data and is updated the majority of patients with type 1 di- as compared with 55% in deceased- annually.Registrationofeachorgantrans- abetes. In contrast, in the non-Leiden donor kidney transplant recipients (9). In plantation is mandatory and coordinated area, consisting of seven transplantation the same registry during 2000–2007, by the government via the Dutch Trans- centers, a kidney transplant alone has recipients of a living-donor kidney trans- plant Foundation. The Dutch Renal Reg- been the preferred treatment, and SPK plant had a better 6-year survival as istry (Registratie Nierfunctievervanging transplantation is performed in a
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