|
1
|
Martinez EJ, Pham PH, Wang JF, Stalter LN, Welch BM, Leverson G, Marka N, Al-Qaoud T, Mandelbrot D, Parajuli S, Sollinger HW, Kaufman DB, Redfield RR, Odorico JS. Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation. Transpl Int 2024; 37:13087. [PMID: 39364120 PMCID: PMC11446817 DOI: 10.3389/ti.2024.13087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/10/2024] [Indexed: 10/05/2024]
Abstract
Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.
Collapse
Affiliation(s)
- Eric J. Martinez
- Anette C and Harold C Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Phuoc H. Pham
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
- Department of Medicine, School of Medicine, Creighton University, Omaha, NE, United States
| | - Jesse F. Wang
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Lily N. Stalter
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Bridget M. Welch
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Glen Leverson
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Nicholas Marka
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Talal Al-Qaoud
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Hans W. Sollinger
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Dixon B. Kaufman
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Robert R. Redfield
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Jon Scott Odorico
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| |
Collapse
|
|
2
|
Pancreas Transplantation in Minorities including Patients with a Type 2 Diabetes Phenotype. URO 2022. [DOI: 10.3390/uro2040026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background: Prior to year 2000, the majority of pancreas transplants (PTx) were performed as simultaneous pancreas-kidney transplants (SPKTs) in Caucasian adults with end stage renal failure secondary to type 1 diabetes mellitus (T1DM) who were middle-aged. In the new millennium, improving outcomes have led to expanded recipient selection that includes patients with a type 2 diabetes mellitus (T2DM) phenotype, which excessively affects minority populations. Methods: Using PubMed® to identify appropriate citations, we performed a literature review of PTx in minorities and in patients with a T2DM phenotype. Results: Mid-term outcomes with SPKT in patients with uremia and circulating C-peptide levels (T2DMphenotype) are comparable to those patients with T1DM although there may exist a selection bias in the former group. Excellent outcomes with SPKT suggests that the pathophysiology of T2DM is heterogeneous with elements consisting of both insulin deficiency and resistance related to beta-cell failure. As a result, increasing endogenous insulin (Cp) production following PTx may lead to freedom checking blood sugars or taking insulin, better metabolic counter-regulation, and improvements in quality of life and life expectancy compared to other available treatment options. Experience with solitary PTx for T2DM or in minorities is limited but largely mirrors the trends reported in SPKT. Conclusions: PTx is a viable treatment option in patients with pancreas endocrine failure who are selected appropriately regardless of diabetes type or recipient race. This review will summarize data that unconventional patient populations with insulin-requiring diabetes may gain value from PTx with an emphasis on contemporary experiences and appropriate selection in minorities in the new millennium.
Collapse
|
|
3
|
Gopal JP, McLean A, Crane J, Herbert P, Papalois V, Dor FJMF, Muthusamy AR. Pancreas Transplantation in Black, Asian and Minority Ethnic Patients-Single Centre Experience in the UK. Transpl Int 2022; 35:10490. [PMID: 35781938 PMCID: PMC9240992 DOI: 10.3389/ti.2022.10490] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022]
Abstract
Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients (n = 171; Caucasians = 118/Black Asian Ethnic Minorities, BAME = 53) from 2006 to 2020 was done. The median follow-up was 80 months. Patient & pancreas graft survival, rejection rate, steroid free maintenance rate, HbA1c, weight gain, and the incidence of secondary diabetic complications post-transplant were compared between the groups. p < 0.003 was considered significant (corrected for multiple hypothesis testing). Immunosuppression consisted of alemtuzumab induction and steroid free maintenance with tacrolimus and mycophenolate mofetil. Pancreas graft & patient survival were equivalent in both the groups. BAME recipients had a higher prevalence of type-2 diabetes mellitus pre-transplant (BAME = 30.19% vs. Caucasians = 0.85%, p < 0.0001), and waited for a similar time to transplantation once waitlisted, although pre-emptive SPK transplantation rate was higher for Caucasian recipients (Caucasians = 78.5% vs. BAME = 0.85%, p < 0.0001). Despite equivalent rejections & steroid usage, BAME recipients gained more weight (BAME = 7.7% vs. Caucasians = 1.8%, p = 0.001), but had similar HbA1c (functioning grafts) at 3-,12-, 36-, and 60-months post-transplant.
Collapse
Affiliation(s)
- Jeevan Prakash Gopal
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Adam McLean
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Jeremy Crane
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Paul Herbert
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Vassilios Papalois
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Frank J. M. F. Dor
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Anand Rathnasamy Muthusamy
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| |
Collapse
|
|
4
|
Pancreas Transplantation for Type 2 Diabetes: A Systematic Review, Critical Gaps in the Literature, and a Path Forward. Transplantation 2022; 106:1916-1934. [PMID: 35576270 DOI: 10.1097/tp.0000000000004113] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Pancreas transplantation in patients with type 2 diabetes (T2D) remains relatively uncommon compared with pancreas transplantation in patients with type 1 diabetes (T1D); however, several studies have suggested similar outcomes between T2D and T1D, and the practice has become increasingly common. Despite this growing interest in pancreas transplantation in T2D, no study has systematically summarized the data to date. We systematically reviewed the literature on pancreas transplantation in T2D patients including patient and graft survival, glycemic control outcomes, and comparisons with outcomes in T2D kidney transplant alone and T1D pancreas transplant recipients. We searched biomedical databases from January 1, 2000, to January 14, 2021, and screened 3314 records, of which 22 full texts and 17 published abstracts met inclusion criteria. Full-text studies were predominantly single center (73%), whereas the remaining most often studied the Organ Procurement and Transplantation Network database. Methodological quality was mixed with frequent concern for selection bias and concern for inconsistent definitions of both T2D and pancreas graft survival across studies. Overall, studies generally reported favorable patient survival, graft survival, and glycemic control outcomes for pancreas transplantation in T2D and expressed a need to better characterize the T2D patients who would benefit most from pancreas transplantation. We suggest guidance for future studies, with the aim of supporting the safe and evidence-based treatment of end-stage T2D and judicious use of scarce resources.
Collapse
|
|
5
|
Gurram V, Gurung K, Rogers J, Farney AC, Orlando G, Jay C, Reeves-Daniel A, Mena-Gutierrez A, Sakhovskaya N, Doares W, Kaczmorski S, Sharda B, Gautreaux MD, Stratta RJ. Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study. Clin Transplant 2021; 36:e14498. [PMID: 34599533 DOI: 10.1111/ctr.14498] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/17/2021] [Accepted: 09/27/2021] [Indexed: 11/27/2022]
Abstract
Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp- (level < 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p = .15), and pancreas graft survival (60% versus 86%, p = .03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p = .026) or rejection (17% Cp+ versus 6.5% Cp-, p = .2). Post-transplant weight gain > 5 kg occurred in 72% of Cp+ versus 26% of Cp- patients (p = .0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.
Collapse
Affiliation(s)
- Venkat Gurram
- Departments of General Surgery, (Section of Transplantation)
| | - Komal Gurung
- Departments of General Surgery, (Section of Transplantation)
| | - Jeffrey Rogers
- Departments of General Surgery, (Section of Transplantation)
| | - Alan C Farney
- Departments of General Surgery, (Section of Transplantation)
| | | | - Colleen Jay
- Departments of General Surgery, (Section of Transplantation)
| | | | | | | | | | | | - Berjesh Sharda
- Departments of General Surgery, (Section of Transplantation)
| | - Michael D Gautreaux
- Department of Pathology, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA
| | | |
Collapse
|
|
6
|
Shyr BS, Shyr BU, Chen SC, Loong CC, Shyr YM, Wang SE. A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus. Hepatobiliary Surg Nutr 2021; 10:443-453. [PMID: 34430523 DOI: 10.21037/hbsn-19-422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 09/19/2019] [Indexed: 11/06/2022]
Abstract
Background Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged. Methods In total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups. Results Majority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups. Conclusions T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.
Collapse
Affiliation(s)
- Bor-Shiuan Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Bor-Uei Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei.,Division of Transplant Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Shih-Chin Chen
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Che-Chuan Loong
- Division of Transplant Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Shin-E Wang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| |
Collapse
|
|
7
|
Cao Y, Liu X, Lan X, Ni K, Li L, Fu Y. Simultaneous pancreas and kidney transplantation for end-stage kidney disease patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Langenbecks Arch Surg 2021; 407:909-925. [PMID: 34279713 PMCID: PMC9151548 DOI: 10.1007/s00423-021-02249-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/13/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE The indications for patients with type 2 diabetes mellitus (T2DM) combined with end-stage kidney disease (ESKD) undertaking simultaneous pancreas and kidney transplantation (SPK) remain an unresolved issue. This study aimed to systematically review the survival outcomes of SPK among T2DM-ESKD patients. METHODS Online databases including PubMed, MEDLINE, EMBASE, and the CENTRAL Library, CNKI, Chinese Biomedical Literature Database, and Wan-Fang database were used to locate the studies of ESKD patients with T2DM undertaking SPK up to May 2021. A third reviewer was consulted if there were disagreements. Data were analyzed with STATA (15.0). RESULTS Nine cohort studies were identified. The pooled 1-year, 3-year, and 5-year patient survival rates of patients with T2DM and ESKD after SPK were 98%, 95%, and 91% respectively. Comparing the treatment effect of SPK between type 1 diabetes mellitus (T1DM) and T2DM, the survival estimates were comparable. For T2DM patients, SPK had a survival advantage compared with KTA. CONCLUSIONS The synthesized clinical outcomes of T2DM patients with ESKD after SPK were relatively better than KTA, but a subset of T2DM-ESKD patients who would benefit the most from SPK was to be defined. PROSPERO registration number CRD42019118321. Date of registration: 14 Jan 2019 (retrospectively registered).
Collapse
Affiliation(s)
- Yu Cao
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Xiaoli Liu
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Xiangyu Lan
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Kaiwen Ni
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Lin Li
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Yingxin Fu
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China.
| |
Collapse
|
|
8
|
Ling JEH, Polkinghorne KR, Kanellis J. Results from an International Survey of Donor and Recipient Eligibility for Solid Organ Pancreas Transplantation. Ann Transplant 2021; 26:e930787. [PMID: 34031355 PMCID: PMC8166651 DOI: 10.12659/aot.930787] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background Current solid organ pancreas transplantation protocols have differing donor criteria for donor pancreas acceptance and recipient eligibility criteria for transplant workup. We quantified this variation and compared current Australia and New Zealand (ANZ) solid pancreas transplant eligibility criteria with current international practice. Material/Methods A survey of donor and recipient eligibility criteria for solid pancreas transplantation was disseminated to 85 transplant units in 23 countries. Responses were grouped by regions (ANZ, North America, Eurotransplant, Europe, United Kingdom) and analyzed for significant differences between regions and for ANZ compared to all other regions. Results Responding UK pancreas transplant units reported the highest mean donor upper age limit (61 years old) and the highest mean donation after cardiac death donor (DCD) age limit (55 years old). All responding UK and USA units utilized DCD pancreas donors and accepted suitable type 2 diabetes (T2DM) recipients for pancreas transplantation; however, this was less common among responding European or Eurotransplant units. ANZ mean standard and DCD pancreas donor upper age limits (47 and 35 years old, respectively) were lower compared to all other regions (54 years old and 48 years old, respectively). Conclusions Pancreas donor age limits, DCD pancreas donor utilization, and transplanting T2DM recipients differ between responding pancreas transplant units. ANZ units have more conservative donor upper age limits compared to other responding units. Increased utilization of DCD pancreas donors and T2DM recipients while standardizing pancreas donor age limits might increase donor numbers and improve access to solid pancreas transplantation both locally and abroad.
Collapse
Affiliation(s)
- Jonathan E H Ling
- Department of Nephrology, Monash Health, Clayton, Victoria, Australia.,Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia
| | - Kevan R Polkinghorne
- Department of Nephrology, Monash Health, Clayton, Victoria, Australia.,Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.,Department of Epidemiology and Preventative Medicine, Monash University, Clayton, Victoria, Australia
| | - John Kanellis
- Department of Nephrology, Monash Health, Clayton, Victoria, Australia.,Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia
| |
Collapse
|
|
9
|
Xie WY, McAlister VC, Fiorini K, Sener A, Luke PP. Elevated C-peptide Levels Are Associated With Acute Rejection in Kidney Pancreas Transplantation. Transplant Proc 2020; 52:987-991. [PMID: 32143871 DOI: 10.1016/j.transproceed.2020.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/10/2019] [Accepted: 01/02/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND We assessed whether allograft rejection or failure can be predicted by an acute increase in C-peptide production from the transplanted pancreas. METHODS Patients with a minimum of 5 years of follow-up post simultaneous pancreas-kidney transplant were identified. C-peptide levels were obtained during clinic visits routinely. Graft failure was defined as return to dependence on insulin therapy or return to dialysis for pancreas and kidney grafts, respectively. Protocol kidney allograft biopsies were performed at 3 and 12 months. For-cause biopsies were also performed. RESULTS Acute rejections were detected in 11 patients on biopsy results of the renal allograft. C-peptide levels drawn prior to documented rejections were significantly higher in patients with acute rejection than patients with borderline or no rejection (P = .006). Receiver operating characteristics curves for C-peptide indicated greater accuracy in predicting rejection than simultaneously drawn serum creatinine or lipase. CONCLUSIONS Higher C-peptide levels in simultaneous pancreas-kidney recipients is associated with acute rejection vs nonrejection.
Collapse
Affiliation(s)
- Wen Y Xie
- Department of Urology, London Health Sciences Center, London, Ontario, Canada; University of Western Ontario, London, Ontario, Canada
| | - Vivian C McAlister
- University of Western Ontario, London, Ontario, Canada; Department of General Surgery, London Health Sciences Center, London, Ontario, Canada
| | - Kyle Fiorini
- Department of Urology, London Health Sciences Center, London, Ontario, Canada
| | - Alp Sener
- Department of Urology, London Health Sciences Center, London, Ontario, Canada; University of Western Ontario, London, Ontario, Canada
| | - Patrick P Luke
- Department of Urology, London Health Sciences Center, London, Ontario, Canada; University of Western Ontario, London, Ontario, Canada.
| |
Collapse
|
|
10
|
Hau HM, Jahn N, Brunotte M, Lederer AA, Sucher E, Rasche FM, Seehofer D, Sucher R. Short and long-term metabolic outcomes in patients with type 1 and type 2 diabetes receiving a simultaneous pancreas kidney allograft. BMC Endocr Disord 2020; 20:30. [PMID: 32106853 PMCID: PMC7045477 DOI: 10.1186/s12902-020-0506-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 02/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease. METHODS Medical data (2001-2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period. RESULTS Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period. CONCLUSION Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.
Collapse
Affiliation(s)
- Hans-Michael Hau
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Dresden, Fetcherstrasse 74, 01307 Dresden, Germany
| | - Nora Jahn
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Maximilian Brunotte
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
- Department of Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Andri Arnosson Lederer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Elisabeth Sucher
- Department of Gastroenterology and Rheumatology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Franz Maximilian Rasche
- Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Diabetology and Nephrology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Robert Sucher
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| |
Collapse
|
|
11
|
Rohan V, Taber D, Palanisamy A, Mcgillicuddy J, Chavin K, Baliga P, Bratton C. Impact of Type 1 and Type 2 Diabetes Mellitus on Pancreas Transplant Outcomes. EXP CLIN TRANSPLANT 2019; 17:796-802. [DOI: 10.6002/ect.2017.0296] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
|
|
12
|
Abstract
PURPOSE OF REVIEW Pancreas transplantation in type 2 diabetes mellitus (T2DM) candidates remains disproportionately lower than in type 1 diabetes mellitus (T1DM); however, outcomes in carefully selected patients mirrors that of T1DM. Despite the 2014 United Network for Organ Sharing (UNOS) eligibility criteria for simultaneous pancreas/kidney transplant (SPK) transplantation in T2DM patients, an expected increase in the number of transplants was not observed. RECENT FINDINGS In an updated International Pancreas and Transplant Registry (IPTR) analysis, 1514 primary deceased donor pancreas transplants were performed in T2DM recipients [1995-2015, SPK 88%, pancreas after kidney (PAK) 9%, pancreas transplant alone (PTA) 3%]. In contrast to the declining number of SPK transplants for T1DM, the number of primary SPK transplants in T2DM patients is increasing over time in the USA. Improvement over time was noted for T2DM SPK patient and graft survival, and the rate of technical failures decreased, paralleling similar overall trends for pancreas transplants in general. Long-term follow-up data of pancreas outcomes in C-peptide positive vs. negative demonstrate noninferior outcomes. BMI does not appear to impact outcomes in carefully selected T2DM candidates. SUMMARY The current UNOS regulations that currently limit access of T2DM to pancreas transplantation based on strict BMI criteria and C-peptide levels need to be liberated.
Collapse
|
|
13
|
Abstract
β cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of approximately 85% and 50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection, and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation offers a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue. β cell clusters derived from embryonic or induced pluripotent stem cells represent another promising unlimited source of insulin producing cells, but clinical application is pending further advances in the function of the β cell like clusters. Exciting developments and rapid progress in all areas of β cell replacement prompted a lively debate by members of the young investigator committee of the International Pancreas and Islet Transplant Association at the 15th International Pancreas and Islet Transplant Association Congress in Melbourne and at the 26th international congress of The Transplant Society in Hong Kong. This international group of young investigators debated which modality of β cell replacement would predominate the landscape in 10 years, and their arguments are summarized here.
Collapse
|
|
14
|
Gruessner AC, Laftavi MR, Pankewycz O, Gruessner RWG. Simultaneous Pancreas and Kidney Transplantation-Is It a Treatment Option for Patients With Type 2 Diabetes Mellitus? An Analysis of the International Pancreas Transplant Registry. Curr Diab Rep 2017; 17:44. [PMID: 28478590 DOI: 10.1007/s11892-017-0864-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Pancreas transplantation remains the best long-term treatment option to achieve euglycemia and freedom from insulin in patients with labile diabetes mellitus. It is an approved procedure for type 1 (T1DM), but it is still considered controversial for type 2 diabetes mellitus (T2DM). RECENT FINDINGS This study analyzed all primary deceased donor pancreas transplants in patients with T2DM reported to IPTR/UNOS between 1995 and 2015. Characteristics, outcomes, and risk factors over time were determined using univariate and multivariate methods. The focus was on simultaneous pancreas/kidney (SPK) transplants, the most common pancreas transplant category. Patient, pancreas, and kidney graft survival rates increased significantly over time and reached 95.8, 83.3, and 91.1%, respectively, at 3 years posttransplant for transplants performed between 2009 and 2015. SPK is a safe procedure with excellent pancreas and kidney graft outcome in patients with T2DM. The procedure restores euglycemia and freedom from insulin and dialysis. Based on our results, SPK should be offered to more uremic patients with labile T2DM.
Collapse
Affiliation(s)
- Angelika C Gruessner
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA.
| | - Mark R Laftavi
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA
| | - Oleh Pankewycz
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Rainer W G Gruessner
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA
| |
Collapse
|
|
15
|
Chakkera HA, Kudva YC, Chang YHH, Heilman RL, Singer AL, Mathur AK, Hewitt WR, Khamash HA, Huskey JL, Katariya NN, Moss AA, Behmen S, Reddy KS. Glucose homeostasis after simultaneous pancreas and kidney transplantation: a comparison of subjects with C-peptide-positive non-type 1 diabetes mellitus and type 1 diabetes mellitus. Clin Transplant 2015; 30:52-9. [DOI: 10.1111/ctr.12658] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2015] [Indexed: 11/30/2022]
Affiliation(s)
| | - Yogish C. Kudva
- Division of Endocrinology and Metabolic Diseases; Mayo Clinic; Rochester MN USA
| | - Yu-Hui H. Chang
- Department of Research Biostatistics; Mayo Clinic; Phoenix AZ USA
| | | | | | - Amit K. Mathur
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
| | | | | | | | | | - Adyr A. Moss
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
| | | | - Kunam S. Reddy
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
| |
Collapse
|
|
16
|
Gullo-Neto S, Padoin AV, Queiroz de Carvalho JE, Wendling R, Traesel MA, Kroth L, Miranda C, Balestro AC, Siqueira R, Chao Lisot B, Lima S, Mottin CC, Saitovitch D. Metabolic surgery for the treatment of type 2 diabetes in pancreas after kidney transplant candidates. Transplant Proc 2015; 46:1741-4. [PMID: 25131025 DOI: 10.1016/j.transproceed.2014.05.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM) in patients not morbidly obese (BMI <35) has been widely studied. Taking into account that ∼12% of pancreas transplants are performed in patients with T2DM, our goal was to evaluate the impact of metabolic surgery on the management of obese patients with T2DM on waiting lists for a pancreas transplant. We performed a Roux-en-Y gastrointestinal bypass in 5 patients with insulin-dependent T2DM who were candidates for pancreas after kidney transplant and with a BMI <35. Three patients became insulin independent by the end of the first year while the other 2 reduced their insulin requirements by 70%. Furthermore, all patients achieved improved control of lipid levels. We concluded that the surgery was effective in controlling blood glucose and lipid metabolism in these obese T2DM kidney transplant recipients. In this population, a pancreas transplant, along with its associated morbidity, may be avoided.
Collapse
Affiliation(s)
- S Gullo-Neto
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; General and Digestive Tract Surgery Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | - A Vontobel Padoin
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; General and Digestive Tract Surgery Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | | | - R Wendling
- Anesthesiology Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | - M A Traesel
- Nephrology Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | - L Kroth
- Nephrology Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | - C Miranda
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - A Colombo Balestro
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - R Siqueira
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - B Chao Lisot
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - S Lima
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - C Corá Mottin
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; General and Digestive Tract Surgery Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil
| | - D Saitovitch
- Medical School of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Nephrology Service, São Lucas Hospital-PUCRS, Porto Alegre, Brazil.
| |
Collapse
|
|
17
|
|
|
18
|
Weems P, Cooper M. Pancreas transplantation in type II diabetes mellitus. World J Transplant 2014; 4:216-221. [PMID: 25540731 PMCID: PMC4274592 DOI: 10.5500/wjt.v4.i4.216] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Revised: 06/04/2014] [Accepted: 07/15/2014] [Indexed: 02/05/2023] Open
Abstract
Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.
Collapse
|
|
19
|
Stratta RJ, Rogers J, Farney AC, Orlando G, El-Hennawy H, Gautreaux MD, Reeves-Daniel A, Palanisamy A, Iskandar SS, Bodner JK. Pancreas transplantation in C-peptide positive patients: does "type" of diabetes really matter? J Am Coll Surg 2014; 220:716-27. [PMID: 25667140 DOI: 10.1016/j.jamcollsurg.2014.12.020] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 12/15/2014] [Indexed: 01/01/2023]
Abstract
BACKGROUND In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT). STUDY DESIGN We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥ 2.0 ng/mL or < 2.0 ng/mL. RESULTS From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥ 2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥ 5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2). CONCLUSIONS Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be used exclusively to determine candidacy for SPKT.
Collapse
Affiliation(s)
- Robert J Stratta
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC.
| | - Jeffrey Rogers
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Alan C Farney
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Giuseppe Orlando
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Hany El-Hennawy
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael D Gautreaux
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC; Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Amber Reeves-Daniel
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Amudha Palanisamy
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Samy S Iskandar
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jason K Bodner
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| |
Collapse
|
|
20
|
Rogers J, Farney AC, Orlando G, Iskandar SS, Doares W, Gautreaux MD, Kaczmorski S, Reeves-Daniel A, Palanisamy A, Stratta RJ. Pancreas transplantation: The Wake Forest experience in the new millennium. World J Diabetes 2014; 5:951-961. [PMID: 25512802 PMCID: PMC4265886 DOI: 10.4239/wjd.v5.i6.951] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 07/09/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression.
METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide.
RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.
CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.
Collapse
|
|
21
|
Otsuki K, Yoshikawa K, Kenmoshi T, Akutsu N, Maruyama M, Asano T, Saigo K, Hasegawa M, Aoyama H, Matsumoto I, Ito T, Uchino Y. Evaluation of insulin independence using 11C-methionine positron emission tomography after living-donor and brain-dead donor pancreas transplantation. Transplant Proc 2014; 46:1913-6. [PMID: 25131069 DOI: 10.1016/j.transproceed.2014.05.069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.
Collapse
Affiliation(s)
- K Otsuki
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan.
| | - K Yoshikawa
- National Institute of Radiological Sciences, Chiba, Japan
| | - T Kenmoshi
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - N Akutsu
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Maruyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Asano
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - K Saigo
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Hasegawa
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - H Aoyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - I Matsumoto
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Ito
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - Y Uchino
- Chiba Ryogo Center, PET Imaging Division, Chiba, Japan
| |
Collapse
|
|
22
|
Fourtounas C. Transplant options for patients with type 2 diabetes and chronic kidney disease. World J Transplant 2014; 4:102-110. [PMID: 25032099 PMCID: PMC4094945 DOI: 10.5500/wjt.v4.i2.102] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 03/20/2014] [Accepted: 05/14/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic kidney disease (CKD) has become a real epidemic around the world, mainly due to ageing and diabetic nephropathy. Although diabetic nephropathy due to type 1 diabetes mellitus (T1DM) has been studied more extensively, the vast majority of the diabetic CKD patients suffer from type 2 diabetes mellitus (T2DM). Renal transplantation has been established as a first line treatment for diabetic nephropathy unless there are major contraindications and provides not only a better quality of life, but also a significant survival advantage over dialysis. However, T2DM patients are less likely to be referred for renal transplantation as they are usually older, obese and present significant comorbidities. As pre-emptive renal transplantation presents a clear survival advantage over dialysis, all T2DM patients with CKD should be referred for early evaluation by a transplant center. The transplant center should have enough time in order to examine their eligibility focusing on special issues related with diabetic nephropathy and explore the best options for each patient. Living donor kidney transplantation should always be considered as the first line treatment. Otherwise, the patient should be listed for deceased donor kidney transplantation. Recent progress in transplantation medicine has improved the "transplant menu" for T2DM patients with diabetic nephropathy and there is an ongoing discussion about the place of simultaneous pancreas kidney (SPK) transplantation in well selected patients. The initial hesitations about the different pathophysiology of T2DM have been forgotten due to the almost similar short- and long-term results with T1DM patients. However, there is still a long way and a lot of ethical and logistical issues before establishing SPK transplantation as an ordinary treatment for T2DM patients. In addition recent advances in bariatric surgery may offer new options for severely obese T2DM patients with CKD. Nevertheless, the existing data for T2DM patients with advanced CKD are rather scarce and bariatric surgery should not be considered as a cure for diabetic nephropathy, but only as a bridge for renal transplantation.
Collapse
|
|
23
|
Sayed BA, Turgeon NA. Pancreas Transplantation of Non-Traditional Recipients. CURRENT TRANSPLANTATION REPORTS 2014. [DOI: 10.1007/s40472-014-0011-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
24
|
Abstract
Transplantation of the whole vascularized pancreas can provide insulin secretion in patients with insulin-dependent, type 1 diabetes mellitus (T1D). It restores euglycemia in most patients, with the potential to impact the chronic diabetic complications and quality of life. Pancreas transplantation (PT) is presently controversial for type 2 diabetes mellitus (T2D). For those patients with severe glycemic dysregulation, T2D can be associated with the same life-threatening sequelae as T1D such as severe hypoglycemia and kidney failure that could be corrected by pancreas (and kidney) transplantation. Thus, clinical indications and patient selection criteria are very important. This chapter will review the current status of PT for T2D and discuss the options and evolution of transplant perspectives.
Collapse
Affiliation(s)
- Gaetano Ciancio
- The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA,
| | | |
Collapse
|
|
25
|
Abstract
PURPOSE OF REVIEW This review will provide evidence that selected patients with type 2 diabetes mellitus (T2DM) may benefit from vascularized pancreas transplantation (PTX). RECENT FINDINGS Initial experience with simultaneous pancreas-kidney transplantation (SPKT) in patients with T2DM and end-stage renal disease (ESRD) suggested that augmentation of endogenous insulin production by PTX in patients with C-peptide-positive, insulin-requiring diabetes resulted in insulin independence, improved glucose counter-regulation, and enhanced quality of life. A number of single-center retrospective studies have documented equivalent outcomes in patients with either type 1 diabetes mellitus (T1DM) or T2DM undergoing predominantly SPKT, although clearly a selection bias exists for patients in the latter category. Selection criteria for SPKT in T2DM include patients less than 55-60 years of age with a BMI less than 30-32 kg/m², insulin-requiring for a minimum of 5 years with a total daily insulin requirement less than 1 u/kg/day, a fasting C-peptide level less than 10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of 'complicated' diabetes. Data from the International Pancreas Transplant Registry show that up to 7% of SPKT recipients are classified as having T2DM and that outcomes in these patients are comparable to those undergoing SPKT and classified as having T1DM. SUMMARY Consequently, characterization of the 'type' of diabetes may be irrelevant and insulin-requiring diabetic patients with ESRD should be evaluated for PTX based exclusively on their predicted ability to tolerate the surgical procedure and requisite immunosuppression as well as comply with a stringent posttransplant follow-up regimen.
Collapse
|
|
26
|
Light J, Tucker M. Simultaneous pancreas kidney transplants in diabetic patients with end-stage renal disease: the 20-yr experience. Clin Transplant 2013; 27:E256-63. [PMID: 23480129 DOI: 10.1111/ctr.12100] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2012] [Indexed: 02/06/2023]
Abstract
INTRODUCTION We are reporting the results over a 20 yr period of simultaneous pancreas-kidney transplants in patients with end-stage renal disease and diabetes mellitus. The outcomes of the transplants, performed between 1989 and 2008, are stratified by pretransplant c-peptide value. METHODS One hundred and seventy-three patients with end-stage renal disease due to diabetes, and were stratified according to undetectable c-peptide (x < 0.8 ng/mL) and detectable c-peptide (x > 0.8 ng/mL) levels. RESULTS Patients with detectable c-peptide (x > 0.8 ng/mL) were the oldest at diabetes diagnosis (24.2 vs. 15.4 yr, p < 0.0001), and oldest at transplant (42.8 vs. 38.5, p < 0.0001) had fewer years of insulin use (19.19 vs. 22.57 yr, p = 0.012), and were heavier pre transplant (BMI: 26.09 vs. 23.1, p < 0.0001), and heavier post transplant (29.8 vs. 24.7, p < 0.0001). Those with detectable c-peptide levels (x > 0.8 ng/mL) had better graft survival than those with an undetectable c-peptide level (x < 0.8 ng/mL), p = 0.064; while those with undetectable levels, had better patient survival than those with detectable c-peptide levels (p = 0.019). CONCLUSION Despite the differences between groups by BMI, age of onset of insulin use, and age at transplant, there was a difference in patient but not graft survival within the 20 yr follow-up period.
Collapse
Affiliation(s)
- Jimmy Light
- Division of Transplantation, Washington Hospital Center, Washington, DC 20010, USA
| | | |
Collapse
|
|
27
|
Abstract
SPK transplant is the definitive treatment of type 1 diabetes combined with end-stage renal disease. Long-term graft function can lead to improvement in diabetes-related complications and, in patients younger than 50 years, can lead to improved overall survival. PAK transplant and PA transplant do not result in similar improvements in patient survival, but with appropriate patient selection, they can improve quality of life by rendering patients insulin-free. Pancreas transplant is associated with more surgical complications and higher perioperative morbidity and mortality than KTA. Therefore, careful donor and recipient selection along with meticulous surgical technique are mandatory for optimal outcomes.
Collapse
Affiliation(s)
- Kiran K Dhanireddy
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| |
Collapse
|
|
28
|
Wiseman AC, Gralla J. Simultaneous pancreas kidney transplant versus other kidney transplant options in patients with type 2 diabetes. Clin J Am Soc Nephrol 2012; 7:656-64. [PMID: 22344508 DOI: 10.2215/cjn.08310811] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND OBJECTIVES Current organ allocation policy prioritizes placement of kidneys (with pancreas) to patients listed for simultaneous pancreas-kidney transplantation (SPK). Patients with type 2 diabetes mellitus (T2DM) may undergo SPK, but it is unknown whether these patients enjoy a survival advantage with SPK versus deceased-donor kidney transplantation alone (DDKA) or living-donor kidney transplantation alone (LDKA). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the Scientific Registry of Transplant Recipients database, patients with T2DM, age 18-59 years, body mass index 18-30 kg/m(2), who underwent SPK, DDKA, or LDKA from 2000 through 2008 were identified. Five-year patient and kidney graft survival rates were compared, and multivariable analysis was performed to determine donor, recipient, and transplant factors influencing these outcomes. RESULTS Of 6416 patients identified, 4005, 1987, and 424 underwent DDKA, LDKA, and SPK, respectively. On unadjusted analysis, patient and kidney graft survival rates were superior for LDKA versus SPK, whereas patient but not graft survival was higher for SPK versus DDKA. On multivariable analysis, survival advantage for SPK versus DDKA was related not to pancreas transplantation but younger donor and recipient ages in the SPK cohort. CONCLUSIONS Good outcomes can occur with SPK in selected patients with T2DM, but no patient or graft survival advantage is provided by added pancreas transplantation compared with DDKA; outcomes were superior with LDKA. These results support cautious use of SPK in T2DM when LDKA is not an option, with close oversight of the effect of kidney (with pancreas) allocation priority over other transplant candidates.
Collapse
Affiliation(s)
- Alexander C Wiseman
- Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, 80045, USA.
| | | |
Collapse
|
|
29
|
Rogers J, Farney AC, Al-Geizawi S, Iskandar SS, Doares W, Gautreaux MD, Hart L, Kaczmorski S, Reeves-Daniel A, Winfrey S, Ghanta M, Adams PL, Stratta RJ. Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center. Rev Diabet Stud 2011; 8:17-27. [PMID: 21720669 DOI: 10.1900/rds.2011.8.17] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.
Collapse
Affiliation(s)
- Jeffrey Rogers
- Department of General Surgery, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Sampaio MS, Kuo HT, Bunnapradist S. Outcomes of simultaneous pancreas-kidney transplantation in type 2 diabetic recipients. Clin J Am Soc Nephrol 2011; 6:1198-206. [PMID: 21441123 DOI: 10.2215/cjn.06860810] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Type 2 diabetic patients with end-stage renal disease may receive a simultaneous pancreas-kidney (SPK) transplant. However, outcomes are not well described. Risks for death and graft failure were examined in SPK type 2 diabetic recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the United Network for Organ Sharing database, outcomes of SPK transplants were compared between type 2 and type 1 diabetic recipients. All primary SPK adult recipients transplanted between 2000 and 2007 (n=6756) were stratified according to end-stage pancreas disease diagnosis (type 1: n=6141, type 2: n=582). Posttransplant complications and risks for death and kidney/pancreas graft failure were compared. RESULTS Of the 6756 SPK transplants, 8.6% were performed in recipients with a type 2 diabetes diagnosis. Rates of delayed kidney graft function and primary kidney nonfunction were higher in the type 2 diabetics. Five-year overall and death-censored kidney graft survival were inferior in type 2 diabetics. After adjustment for other risk factors, including recipient (age, race, body weight, dialysis time, and cardiovascular comorbidities), donor, and transplant immune characteristics, type 2 diabetes was not associated with increased risk for death or kidney or pancreas failure when compared with type 1 diabetic recipients. CONCLUSIONS After adjustment for other risk factors, SPK recipients with type 2 diabetes diagnosis were not at increased risk for death, kidney failure, or pancreas failure when compared with recipients with type 1 diabetes.
Collapse
Affiliation(s)
- Marcelo Santos Sampaio
- Department of Medicine, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California 90024, USA
| | | | | |
Collapse
|
|
31
|
Fridell JA, Mangus RS, Taber TE, Goble ML, Milgrom ML, Good J, Vetor R, Powelson JA. Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation. Clin Transplant 2011; 25:E366-74. [DOI: 10.1111/j.1399-0012.2011.01422.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
|
|
32
|
Jahansouz C, Kumer SC, Ellenbogen M, Brayman KL. Evolution of β-Cell Replacement Therapy in Diabetes Mellitus: Pancreas Transplantation. Diabetes Technol Ther 2011; 13:395-418. [PMID: 21299398 DOI: 10.1089/dia.2010.0133] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus remains one of the leading causes of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention, approximately 23.6 million people in the United States are affected. Of these individuals, 5-10% have been diagnosed with type 1 diabetes mellitus (TIDM), an autoimmune disease. Although it often appears in childhood, T1DM may manifest at any age. The effects of T1DM can be devastating, as the disease often leads to significant secondary complications, morbidity, and decreased quality of life. Since the late 1960s, surgical treatment for diabetes mellitus has continued to evolve and has become a viable alternative to chronic insulin administration. In this review, the historical evolution, current status, graft efficacy, benefits, and complications of pancreas transplantation are explored.
Collapse
Affiliation(s)
- Cyrus Jahansouz
- University of Virginia School of Medicine, Charlottesville, Virginia, USA.
| | | | | | | |
Collapse
|
|
33
|
Knight R, Lawless A, Patel S, Gaber A. Simultaneous Kidney-Pancreas Transplantation for End-Stage Renal Disease Patients with Insulin-Dependent Diabetes and Detectable C-Peptide. Transplant Proc 2010; 42:4195-6. [DOI: 10.1016/j.transproceed.2010.09.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2010] [Accepted: 09/03/2010] [Indexed: 10/18/2022]
|
|
34
|
Chakkera HA, Bodner JK, Heilman RL, Mulligan DC, Moss AA, Mekeel KL, Mazur MJ, Hamawi K, Ray RM, Beck GL, Reddy KS. Outcomes after simultaneous pancreas and kidney transplantation and the discriminative ability of the C-peptide measurement pretransplant among type 1 and type 2 diabetes mellitus. Transplant Proc 2010; 42:2650-2. [PMID: 20832562 PMCID: PMC3060052 DOI: 10.1016/j.transproceed.2010.04.065] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 04/20/2010] [Indexed: 12/21/2022]
Abstract
BACKGROUND Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease. METHODS To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT. RESULTS Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM. CONCLUSION SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.
Collapse
|
|
35
|
Abstract
The use of pancreas transplantation for type 2 diabetes mellitus is an emerging concept. Several lines of laboratory and clinical evidence suggest that in a carefully selected group of patients, long-term glycemic control and allograft function are similar to that observed for pancreas transplants performed for type 1 diabetes.
Collapse
|