|
1
|
Giri G, Doherty D, Azmi S, Khambalia H, Giuffrida G, Moinuddin Z, van Dellen D. The impact of pancreas transplantation on diabetic complications: A systematic review. Transplant Rev (Orlando) 2025; 39:100910. [PMID: 39864231 DOI: 10.1016/j.trre.2025.100910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 01/15/2025] [Accepted: 01/19/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND Pancreas Transplantation (PT) provides optimal treatment for patients with severe complicated Type 1 Diabetes Mellitus (T1DM). Restoration of beta-cell mass allows return to euglycaemia and insulin independence. We aimed to examine its impact on the secondary complications associated with severe T1DM including diabetic eye disease, neuropathy and cardiovascular disease. METHODS A database search using MedLINE to identify publications to April 2023 was conducted. Searches were performed using MeSH terms 'Pancreas Transplantation' AND 'Diabetes Mellitus, Type 1' 'Diabetic Retinopathy' OR 'Heart Disease' OR 'Cardiovascular Diseases' OR 'Peripheral Vascular Disease' OR "Amputation' OR 'Neuropathy." RESULTS All articles were retrospective with 51.1 % (n = 23) case control studies and 48.9 % (n = 22) cohort studies. 82.2 % (n = 37) examined simultaneous pancreas and kidney (SPK) transplantation and 17.8 % (n = 8) analysed pancreas transplant alone (PTA). Heterogenous outcomes metrics were employed. 15 studies examined diabetic retinopathy (DR) with 53.3 % (n = 8) demonstrated improvements after PT, while the remainder (n = 7) exhibited stabilisation. 16 studies assessed neuropathy and 87.5 % (n = 14) demonstrated beneficial effects of PT on nerve conduction studies, vibration perception threshold or corneal confocal microscopy. There was a positive effect on cardiovascular disease by reduction in the incidence of cardiac events, improvement in metabolic profile and increased left ventricular ejection fraction. 14 studies examined cardiovascular disease (71.4 % (n = 10) improvement; 14.2 % (n = 2) stabilisation; 14.2 % (n = 2) progression). CONCLUSION SPK and PTA have beneficial effects in ameliorating or stabilising diabetes complications. Future work should seek to reduce heterogeneity of outcome metrics assessing T1DM complication profile to facilitate robust comparison of beta-cell replacement interventions.
Collapse
Affiliation(s)
- Gayathri Giri
- Faculty of Biology, Medicine & Health, University of Manchester, UK
| | - Daniel Doherty
- Faculty of Biology, Medicine & Health, University of Manchester, UK; Manchester Centre for Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK.
| | - Shazli Azmi
- Department of Diabetes & Endocrinology, Manchester University NHS Foundation Trust, UK
| | - Hussein Khambalia
- Faculty of Biology, Medicine & Health, University of Manchester, UK; Manchester Centre for Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK
| | - Giuseppe Giuffrida
- Manchester Centre for Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK
| | - Zia Moinuddin
- Faculty of Biology, Medicine & Health, University of Manchester, UK; Manchester Centre for Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK
| | - David van Dellen
- Faculty of Biology, Medicine & Health, University of Manchester, UK; Manchester Centre for Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK
| |
Collapse
|
|
2
|
Diabetic Neuropathy Is Independently Associated With Worse Graft Outcomes and Incident Cardiovascular Disease After Pancreas Transplantation: A Retrospective Cohort Study in Type 1 Diabetes. Transplantation 2023; 107:475-484. [PMID: 35969040 DOI: 10.1097/tp.0000000000004275] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Information about the impact of diabetic neuropathy (DN) on outcomes after pancreas transplantation (PT) is scarce. We assessed the independent relationship between DN markers with both graft survival and incident cardiovascular disease (CVD) after transplantation. METHODS A cohort study in individuals with type 1 diabetes and end-stage kidney disease who underwent PT between 1999 and 2015 was conducted. DN was assessed with vibration perception thresholds (VPTs) and orthostatic hypotension (pre-PT and 6 mo, 2-3, 5-6, and 8-10 y after transplantation). Pretransplantation and posttransplantation DN markers were related with graft failure/dysfunction and incident CVD during follow-up. RESULTS We included 187 participants (70% men, age 39.9 ± 7.1 y, diabetes duration 27.1 y), with a median follow-up of 11.3 y. Abnormal VPTs (≥25 V) were observed in 53%. After transplantation, VPTs improved (22.4 ± 8.4 pretransplant versus 16.1 ± 6.1 V at 8-10 y post-PT; P < 0.001); additionally, the prevalence of abnormal VPTs decreased (53% pretransplant versus 24.4% at 8-10 y; P < 0.001). After adjusting for age, sex, diabetes duration, blood pressure, body mass index, and previous CVD, pretransplant VPTs ≥25 V were independently associated with pancreas graft failure/dysfunction (hazard ratio [HR], 2.01 [1.01-4.00]) and incident CVD (HR, 2.57 [1.17-5.64]). Furthermore, persistent abnormal VPTs after 6 mo posttransplantation were associated with the worst outcomes (HR, 2.80 [1.25-6.23] and HR, 3.19 [1.14-8.96], for graft failure/dysfunction and incident CVD, respectively). CONCLUSIONS In individuals with type 1 diabetes and end-stage kidney disease, PT was associated with an improvement of VPTs. This simple and widely available DN study was independently associated with pancreas graft function and CVD posttransplantation.
Collapse
|
|
3
|
Boggi U, Vistoli F, Andres A, Arbogast HP, Badet L, Baronti W, Bartlett ST, Benedetti E, Branchereau J, Burke GW, Buron F, Caldara R, Cardillo M, Casanova D, Cipriani F, Cooper M, Cupisti A, Davide J, Drachenberg C, de Koning EJP, Ettorre GM, Fernandez Cruz L, Fridell JA, Friend PJ, Furian L, Gaber OA, Gruessner AC, Gruessner RW, Gunton JE, Han D, Iacopi S, Kauffmann EF, Kaufman D, Kenmochi T, Khambalia HA, Lai Q, Langer RM, Maffi P, Marselli L, Menichetti F, Miccoli M, Mittal S, Morelon E, Napoli N, Neri F, Oberholzer J, Odorico JS, Öllinger R, Oniscu G, Orlando G, Ortenzi M, Perosa M, Perrone VG, Pleass H, Redfield RR, Ricci C, Rigotti P, Paul Robertson R, Ross LF, Rossi M, Saudek F, Scalea JR, Schenker P, Secchi A, Socci C, Sousa Silva D, Squifflet JP, Stock PG, Stratta RJ, Terrenzio C, Uva P, Watson CJ, White SA, Marchetti P, Kandaswamy R, Berney T. First World Consensus Conference on pancreas transplantation: Part II - recommendations. Am J Transplant 2021; 21 Suppl 3:17-59. [PMID: 34245223 PMCID: PMC8518376 DOI: 10.1111/ajt.16750] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 02/07/2023]
Abstract
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.
Collapse
|
|
4
|
Abstract
BACKGROUND Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). METHODS We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search terms included small fiber neuropathy,diffuse peripheral neuropathy, quantitative sensory testing, nerve conduction testing, intra-epidermal nerve fiber density, corneal confocal reflectance microscopy, aldose reductase inhbitors, nerve growth factor, alpha-lipoic acid, ruboxistaurin, nerve growth factor antibody, and cibinetide. RESULTS Over the past half century, there have been a number of agents undergoing unsuccessful trials for treatment of DPN.There are several approved agents for relief of pain caused by diabetic neuropathy, but these do not affect the pathologic process. EXPERT OPINION The failure to find treatments for diabetic neuropathy can be ascribed to (1) the complexity of design of studies and (2) the slow progression of the condition, necessitating long duration trials to prove efficacy.We propose a modification of the regulatory process to permit early introduction of agents with demonstrated safety and suggestion of benefit as well as prolongation of marketing exclusivity while long term trials are in progress to prove efficacy.
Collapse
Affiliation(s)
- Marc S Rendell
- The Association for Diabetes Investigators , Newport Coast, California. USA
| |
Collapse
|
|
5
|
Fensom B, Harris C, Thompson SE, Al Mehthel M, Thompson DM. Islet cell transplantation improves nerve conduction velocity in type 1 diabetes compared with intensive medical therapy over six years. Diabetes Res Clin Pract 2016; 122:101-105. [PMID: 27825059 DOI: 10.1016/j.diabres.2016.10.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 10/02/2016] [Accepted: 10/12/2016] [Indexed: 11/21/2022]
Abstract
BACKGROUND Neuropathy is a common diabetic complication that can result in significant disability. Few treatment options exist to reverse this process. METHODS We conducted a one-way crossover cohort study comparing intensive medical treatment and islet cell transplantation for type 1 diabetes on the change in nerve conduction velocity over six years. FINDINGS For subjects with some neuropathy at baseline (Z score below -1), nerve conduction velocity significantly improved post-transplant (slope (0.073±0.042) while it worsened in medically treated patients (-0.136±0.081) (p<.05). INTERPRETATION Islet cell transplantation improves nerve conduction velocity and could be further investigated as a treatment for neuropathy in type 1 diabetes.
Collapse
Affiliation(s)
- Blake Fensom
- Department of Medicine, Vancouver General Hospital and University of British Columbia, Canada
| | - Claire Harris
- Department of Medicine, Vancouver General Hospital and University of British Columbia, Canada
| | - Sharon E Thompson
- Department of Medicine, Vancouver General Hospital and University of British Columbia, Canada
| | - Mohammed Al Mehthel
- Department of Medicine, Vancouver General Hospital and University of British Columbia, Canada
| | - David M Thompson
- Department of Medicine, Vancouver General Hospital and University of British Columbia, Canada.
| |
Collapse
|
|
6
|
Jacewicz M, Marino CR. Neurologic complications of pancreas and small bowel transplantation. HANDBOOK OF CLINICAL NEUROLOGY 2014; 121:1277-1293. [PMID: 24365419 DOI: 10.1016/b978-0-7020-4088-7.00087-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
In the past decade, substantial improvements in patient and graft survival for pancreas and small bowel transplants have been achieved. Despite this progress, many patients still develop neurologic complications in the course of their illness. Small bowel transplants produce more neurologic complications because of the complex metabolic environment in which the procedure is performed and because of the intense immune suppression necessitated by the greater immunogenicity of the intestinal mucosa. Pancreas transplants stabilize and/or improve the signs and symptoms of diabetic neuropathy over time. Because transplantation of the pancreas is often coupled with a kidney transplant and small intestine with liver, neurologic complications in these patients sometimes reflect problems involving the organ partner or both organs. The spectrum of neurologic complications for pancreas and small bowel transplant recipients is similar to other organ transplants but their frequency varies depending on the type of transplant performed.
Collapse
Affiliation(s)
- Michael Jacewicz
- Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
| | - Christopher R Marino
- Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| |
Collapse
|
|
7
|
Pancreas-kidney transplantation is associated with reduced fracture risk compared with kidney-alone transplantation in men with type 1 diabetes. Kidney Int 2013; 83:471-8. [PMID: 23283136 PMCID: PMC3587361 DOI: 10.1038/ki.2012.430] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Both type 1 diabetes mellitus and end stage renal disease are associated with increased fracture risk, likely due to metabolic abnormalities that reduce bone strength. Simultaneous pancreas-kidney transplantation is a treatment of choice for patients with both disorders, yet the effects of simultaneous pancreas-kidney versus kidney transplantation alone on post-transplantation fracture risk are unknown. From the United States Renal Data System we identified 11, 145 adults with type 1 diabetes undergoing transplantation of whom 4,933 had a simultaneous pancreas-kidney while 6, 212 had a kidney alone transplant between 2000 and 2006. Post-transplantation fractures resulting in hospitalization were identified from discharge codes. Time to first fracture was modeled and propensity score adjustment was used to balance covariates between groups. Fractures occurred in significantly fewer (4.7%) of pancreas-kidney compared to kidney-alone transplant (5.9%) cohorts. After gender stratification and adjustment for fracture covariates, pancreas-kidney transplantation was associated with a significant 31% reduction in fracture risk in men (hazard risk 0.69). Older age, white race, prior dialysis and pre transplantation fracture were also associated with increased fracture risk. Prospective studies are needed to determine the gender-specific mechanisms by which pancreas-kidney transplantation reduces fracture risk in men.
Collapse
|
|
8
|
Hartemann A, Attal N, Bouhassira D, Dumont I, Gin H, Jeanne S, Said G, Richard JL. Painful diabetic neuropathy: Diagnosis and management. DIABETES & METABOLISM 2011; 37:377-88. [DOI: 10.1016/j.diabet.2011.06.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Accepted: 06/13/2011] [Indexed: 01/01/2023]
|
|
9
|
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
|
|
10
|
Abstract
Chronic kidney disease (CKD) is a critical and rapidly growing global health problem. Neurological complications occur in almost all patients with severe CKD, potentially affecting all levels of the nervous system, from the CNS through to the PNS. Cognitive impairment, manifesting typically as a vascular dementia, develops in a considerable proportion of patients on dialysis, and improves with renal transplantation. Patients on dialysis are generally weaker, less active and have reduced exercise capacity compared with healthy individuals. Peripheral neuropathy manifests in almost all such patients, leading to weakness and disability. Better dialysis strategies and dietary modification could improve outcomes of transplantation if implemented before surgery. For patients with autonomic neuropathy, specific treatments, including sildenafil for impotence and midodrine for intradialytic hypotension, are effective and well tolerated. Exercise training programs and carnitine supplementation might be beneficial for neuromuscular complications, and restless legs syndrome in CKD responds to dopaminergic agonists and levodopa treatment. The present Review dissects the pathophysiology of neurological complications related to CKD and highlights the spectrum of therapies currently available.
Collapse
Affiliation(s)
- Arun V Krishnan
- Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
| | | |
Collapse
|
|
11
|
|
|
12
|
Abstract
Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin A1c levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events (even with only partial islet function evident). Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pre-transplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the long-term viability and function of the graft to maintain improved glucose control over time.
Collapse
Affiliation(s)
- R Mark Meloche
- Department of Surgery, University of British Columbia, 5th Floor Diamond Centre, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
| |
Collapse
|
|
13
|
Abstract
Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin A1c levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events (even with only partial islet function evident). Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pre-transplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the long-term viability and function of the graft to maintain improved glucose control over time.
Collapse
|
|
14
|
Abstract
Organ transplantation is a procedure that can save and prolong the life of individuals with end-stage heart, lung, liver, kidney, pancreas and small bowel diseases. The goal of transplantation is not only to ensure their survival, but also to offer patients the sort of health they enjoyed before the disease, achieving a good balance between the functional efficacy of the graft and the patient's psychological and physical integrity. Quality of life (QoL) assessments are used to evaluate the physical, psychological and social domains of health, seen as distinct areas that are influenced by a person's experiences, beliefs, expectations and perceptions, and QoL is emerging as a new medical indicator in transplantation medicine too. This review considers changes in overall QoL after organ transplantation, paying special attention to living donor transplantation, pediatric transplantation and particular aspects of QoL after surgery, e.g. sexual function, pregnancy, schooling, sport and work.
Collapse
Affiliation(s)
- Patrizia Burra
- Gastroenterology Section, Department of Surgical and Gastroenterological Sciences, Padua University, Padua, Italy.
| | | |
Collapse
|
|
15
|
Abstract
Pancreas or islet transplantation can provide good glycaemic control and insulin independence. Pancreas transplantation has been associated with improvement in diabetic retinopathy, nephropathy, neuropathy and vasculopathy, but has the associated morbidity of major surgery. Both forms of therapy require long-term immunosuppression and its attendant risks and both achieve insulin independence rates of about 80% at 1 year. Pancreas transplantation at the same time as a renal transplant is a worthwhile option to employ, especially if the diabetes has been difficult to control. Diabetes associated with frequent severe hypoglycaemia or extreme lability, despite optimization of diabetes management, may benefit from either pancreas or islet transplant alone with the latter being the lower-risk procedure. More quantitative measures of hypoglycaemia and lability are now available to facilitate the assessment of the severity of these problems with glucose control. Diabetic patients with renal involvement (macroproteinuria, but no major elevation of creatinine) and unstable diabetes may be helped with an islet or pancreas transplant, but this approach should still be considered experimental and such a transplant may hasten the need for renal replacement therapy. In the setting of well-controlled diabetes and intact renal function, it is difficult to justify pancreas or islet transplant alone given the risks of immunosuppression.
Collapse
Affiliation(s)
- Edmond A Ryan
- Department of Medicine, Clinical Islet Transplant Program, University of Alberta and Capital Health, Edmonton, Alberta, Canada.
| | | | | |
Collapse
|
|
16
|
Eberl N, Piehlmeier W, Dachauer S, König A, Land W, Landgraf R. Blood flow in the skin of type 1 diabetic patients before and after combined pancreas/kidney transplantation. Diabetes Metab Res Rev 2005; 21:525-32. [PMID: 15880479 DOI: 10.1002/dmrr.555] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND To analyze effects of long-term glucose normalization after pancreas transplantation, different parameters of skin microcirculation were assessed by laser Doppler fluxmetry. METHODS Forty-two type 1 diabetic patients after successful simultaneous pancreas/kidney transplantation (Group A, median 32.3 months posttransplant), 28 patients with functioning kidney grafts, but insulin therapy (Group B, median 64.9 months posttransplant) and 13 diabetic pretransplant patients (Group C, median 14.2 months on dialysis) were compared with 33 healthy subjects (Group D). Resting blood flow, postocclusive hyperemia, venoarteriolar response on the right foot and decrease in blood flow during cold pressure test on the left finger was assessed. RESULTS Postocclusive hyperemia, decrease in blood flow during cold pressure test and venoarteriolar response were higher in Group D than in all patient groups. Resting blood flow in Group A was significantly lower than in Groups B and C (following values as median): 3.6 perfusion units (PU) versus 7.4 PU in Group B, p < 0.01 and 12.1 PU in Group C, p < 0.001, respectively, and was not significantly different to controls (Group D, 5.2 PU). Postocclusive hyperemia was higher in Group A than in Groups B and C (266.7% vs 160.0%, p < 0.05 and 79.4% n.s., respectively), but significantly less than in Group D (563.5%). The microangiopathy index-high values reflecting less or no microangiopathy-was significantly higher in Group A than in Groups B and C (11.0 vs 4.3, p < 0.001 and 4.7, p < 0.05, respectively), and was very much comparable to the values in healthy controls (Group D, 10,3). The decrease in blood flow during cold pressure test was higher in Group A compared to Groups B and C (25.2% vs 21.1% and 13.8%, n.s., respectively), but much less than in Group D (65,7%). CONCLUSION These data suggest an improvement without complete normalization of skin microcirculation by long-term blood glucose normalization achieved by pancreas transplantation.
Collapse
Affiliation(s)
- Nicola Eberl
- Department of Internal Medicine Innenstadt, University of Munich, Germany.
| | | | | | | | | | | |
Collapse
|
|
17
|
Marroquin CE, Edwards EB, Collins BH, Desai DM, Tuttle-Newhall JE, Kuo PC. Half-Life Analysis of Pancreas and Kidney Transplants. Transplantation 2005; 80:272-5. [PMID: 16041274 DOI: 10.1097/01.tp.0000165094.94020.03] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Although graft and patient survival data are available for pancreas and kidney transplants, they are rarely reported in terms of half-life. Our aim was to determine whether a more relevant measure of outcome is patient and allograft half-life. Using the data from the Organ Procurement and Transplantation Network Registry on kidney and pancreas transplants from January 1988 to December 1996, patient and graft half-life and 95% confidence intervals were calculated and demographic variables compared. No significant differences were found between demographic variables. Kidneys transplanted in diabetics as a simultaneous kidney-pancreas (SPK) fared better than diabetics receiving a kidney alone (9.6 vs. 6.3 years). Pancreatic graft survival in an SPK pair was better than pancreas after kidney transplant or pancreas transplant alone (11.2 vs. 2.5 years). Because kidney and pancreatic grafts have a longer half-life when transplanted with their mate grafts, we should consider the relative benefits of SPKs over pancreas after kidney transplant or pancreas transplant alone to limit the loss of precious resources.
Collapse
Affiliation(s)
- Carlos E Marroquin
- Duke University Medical Center, Department of Surgery, Durham, NC 27710, USA.
| | | | | | | | | | | |
Collapse
|
|
18
|
Cantarovich D, Karam G, Hourmant M, Dantal J, Blancho G, Giral M, Soulillou JP. Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation. Am J Transplant 2005; 5:1332-8. [PMID: 15888038 DOI: 10.1111/j.1600-6143.2005.00816.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Two steroid-sparing immunosuppressive regimens were prospectively compared in recipients of simultaneous pancreas-kidney transplants, one did not include steroids at all and the other included steroids for the first 3 months following transplantation. All patients received rabbit anti-thymocyte globulin, mycophenolate mofetil (MMF) and cyclosporine. Fifty patients were randomised in an open-label, single center and prospective study. The incidence of biopsy-proven acute rejection during the first 12 months after transplantation was the primary endpoint of the study. The incidence of biopsy-proven acute rejection was 4% in both groups. No statistically significant difference in patient (96 and 100%), kidney (96 and 100%) or pancreas (84 and 92%) survival was observed 1 year after transplantation in the steroid avoidance and steroid withdrawal groups, respectively. The total number of adverse events (including severe ones), length of hospitalization and infectious episodes did not differ between groups. Blood glucose and insulin levels, lipid profile and hemoglobin A1C levels did not differ statistically between the two groups. However, the 1-year serum creatinine level was significantly higher in the steroid avoidance group (132 vs. 114 micromol/L; p = 0.02). Steroid avoidance and steroid withdrawal 3 months after transplantation are safe and effective regimens for diabetic patients with pancreas-kidney transplants.
Collapse
Affiliation(s)
- Diego Cantarovich
- Institut de Transplantation et de Recherche en Transplantation (ITERT), Centre Hospitalier et Universitaire de Nantes, France.
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Abstract
Pancreas transplantation continues to evolve as a strategy in the management of diabetes mellitus. The first combined pancreas-kidney transplant was reported in 1967, but pancreas transplant now represents a number of procedures, each with different indications, risks, benefits, and outcomes. This review will summarize these procedures, including their risks and outcomes in comparison to kidney transplantation alone, and how or if they affect the consequences of diabetes: hyperglycemia, hypoglycemia, and microvascular and macrovascular complications. In addition, the new risks introduced by immunosuppression will be reviewed, including infections, cancer, osteoporosis, reproductive function, and the impact of immunosuppression medications on blood pressure, lipids, and glucose tolerance. It is imperative that an endocrinologist remain involved in the care of the pancreas transplant recipient, even when glucose is normal, because of the myriad of issues encountered post transplant, including ongoing management of diabetic complications, prevention of bone loss, and screening for failure of the pancreas graft with reinstitution of treatment when indicated. Although long-term patient and graft survival have improved greatly after pancreas transplant, a multidisciplinary team is needed to maximize long-term quality, as well as quantity, of life for the pancreas transplant recipient.
Collapse
Affiliation(s)
- Jennifer L Larsen
- Section of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, 983020 Nebraska Medical Center, Omaha, Nebraska 69198-3020, USA.
| |
Collapse
|
|
20
|
Esmatjes E, Flores L, Vidal M, Rodriguez L, Cortés A, Almirall L, Ricart MJ, Gomis R. Hypoglycaemia after pancreas transplantation: usefulness of a continuous glucose monitoring system. Clin Transplant 2003; 17:534-8. [PMID: 14756270 DOI: 10.1046/j.1399-0012.2003.00101.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND After pancreas transplantation (PTx) some patients report occasional symptoms of hypoglycaemia and at times, serious hypoglycaemia. Continuous blood glucose monitoring (CBGM) allows determination of the daily glucose profile and detection of unrecognized hypoglycaemia. The aims of our study were to determine the incidence of hypoglycaemia in PTx and evaluate whether the use of CBGM helps to detect unrecognized nocturnal hypoglycaemia. PATIENTS AND METHODS We studied 12 patients (six males) with normal functioning PTx and kidney transplantation for more than 3 yr, with systemic drainage of endocrine secretion and stable immunosuppression. A 24-h CBGM using a microdialysis technique (GlucoDay, A. Menarini Diagnostics, Florence, Italy) was performed in all the patients. RESULTS Three patients had asymptomatic recorded glucose levels below 3.3 nmol/L during the nocturnal period (01:00-07:00 hours) with the glucose levels during these episodes being 2.6, 2.5 and 2.5 nmol/L, and the duration of nocturnal hypoglycaemia being 27, 62 and 93 min, respectively, rising spontaneously without intervention. Patients with hypoglycaemia presented lower glycosylated haemoglobin levels when compared with those not presenting hypoglycaemic episodes, although basal glucose and insulin levels and insulin antibody titres were similar. In one of the three patients presenting hypoglycaemia CBGM was re-evaluated after including an extra snack at bedtime, with subsequent normalization of the blood glucose profile being observed. CONCLUSION Unrecognized nocturnal hypoglycaemia is relatively frequent in patients with PTx and 24-h CBMG may be useful to detect these episodes.
Collapse
Affiliation(s)
- Enric Esmatjes
- Diabetes Unit, Hospital Clínic Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, C/Villarroel, Barcelona, Spain.
| | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Dyck PJ, Velosa JA, Pach JM, Sterioff S, Larson TS, Norell JE, O'Brien PC, Dyck PJ. Increased weakness after pancreas and kidney transplantation. Transplantation 2001; 72:1403-8. [PMID: 11685112 DOI: 10.1097/00007890-200110270-00013] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.
Collapse
Affiliation(s)
- P J Dyck
- Peripheral Neuropathy Research Center, Department of Ophthalmology, Mayo Clinic, 200 First Street, SW, Rochester MN 55905, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
22
|
White SA, Kimber R, Veitch PS, Nicholson ML. Surgical treatment of diabetes mellitus by islet cell and pancreas transplantation. Postgrad Med J 2001; 77:383-7. [PMID: 11375451 PMCID: PMC1742087 DOI: 10.1136/pmj.77.908.383] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- S A White
- Department of Transplantation Surgery, University of Leicester, UK
| | | | | | | |
Collapse
|
|
23
|
Abstract
We compared a conventional method of measurement of sciatic motor and sensory nerve conduction velocity, with a novel procedure that measures conduction in an 8-mm segment of the rat sural nerve. Conventional procedures gave reductions in velocity of 20% and 14% for motor and sensory fibers, respectively, whereas sural sensory fibers showed a 40% reduction (P <0.05). Changes were attenuated by treatment with either an aldose reductase inhibitor or a gamma-linolenic acid-alpha-lipoic acid conjugate, such that values from conventional procedures were not significantly different from controls and the sural sensory deficit halved. Putative motor fibers of the sural nerve showed no conduction velocity deficit in diabetic rats. Measurement of chronaxie and rheobase in sural sensory fibers revealed mild reductions in excitability in diabetics, with prevention of the chronaxie change by the treatments. Thus, measurement of sensory conduction in distal nerve segments show more profound defects in diabetic rats and may give a truer picture of preventive drug efficacy.
Collapse
Affiliation(s)
- J Patel
- Department of Pharmacology, St. Bartholomews's and Royal London Hospital School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK
| | | |
Collapse
|
|
24
|
Bonham CA, Kapur S, Dodson SF, Dvorchik I, Corry RJ. Potential use of marginal donors for pancreas transplantation. Transplant Proc 1999; 31:612-3. [PMID: 10083259 DOI: 10.1016/s0041-1345(98)01579-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- C A Bonham
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA
| | | | | | | | | |
Collapse
|
|
25
|
Kapur S, Bonham CA, Dodson SF, Dvorchik I, Corry RJ. Strategies to expand the donor pool for pancreas transplantation. Transplantation 1999; 67:284-90. [PMID: 10075595 DOI: 10.1097/00007890-199901270-00017] [Citation(s) in RCA: 68] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. METHODS A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. RESULTS Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. CONCLUSIONS Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.
Collapse
Affiliation(s)
- S Kapur
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, USA
| | | | | | | | | |
Collapse
|
|
26
|
Nymann T, Hathaway DK, Bertorini TE, Shokouh-Amiri MH, Gaber AO. Studies of the impact of pancreas-kidney and kidney transplantation on peripheral nerve conduction in diabetic patients. Transplant Proc 1998; 30:323-4. [PMID: 9532060 DOI: 10.1016/s0041-1345(97)01288-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- T Nymann
- Department of Surgery, and Neurology, University of Tennessee, Memphis 38163, USA
| | | | | | | | | |
Collapse
|
|
27
|
Navarro X, Sutherland DE, Kennedy WR. Long-term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol 1997; 42:727-36. [PMID: 9392572 DOI: 10.1002/ana.410420509] [Citation(s) in RCA: 263] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Restoration of a long-lasting euglycemic state by a functioning pancreatic transplantation (PTx) is the most logical treatment for insulin-dependent diabetes mellitus and for amelioration of secondary complications, including neuropathy. We evaluated neurological function by clinical examination, nerve conduction studies, and autonomic function tests in 115 patients with a functioning PTx and in 92 control patients treated with insulin, at baseline and 1, 2, 3.5, 5, 7, and 10 years later. In control patients, neuropathy progressively worsened during follow-up. The clinical examination score and composite indices of abnormality of motor and sensory nerve conduction decreased significantly at all intervals tested. Autonomic function indices also decreased, but significantly only after 1 year. In patients who received a successful PTx the neuropathy improved. The motor and sensory nerve conduction indices increased significantly at all intervals after transplantation, whereas the clinical examination and autonomic tests improved only slightly. Patients who received either a PTx alone, a PTx after a kidney graft, or simultaneous pancreatic and kidney transplantations improved similarly over the follow-up. These results indicate that a functioning PTx halts the progression and improves the signs of diabetic polyneuropathy by restoration of a normoglycemic state.
Collapse
Affiliation(s)
- X Navarro
- Department of Neurology, University of Minnesota, Minneapolis 55455, USA
| | | | | |
Collapse
|
|
28
|
Sugitani A, Gritsch HA, Egidi F, Shapiro R, Corry RJ. En bloc pancreas and kidney transplantation in a patient with limited vascular access. Transplantation 1997; 63:1683-5. [PMID: 9197366 DOI: 10.1097/00007890-199706150-00024] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We report a successful en bloc pancreas and kidney transplantation on a type I diabetic patient with advanced peripheral arterial calcific disease, who had frequent life-threatening episodes of hypoglycemia. The en bloc double organ, created by joining the graft renal artery to the arterial Y graft of the pancreas, was implanted to the proximal left common iliac artery, which was the only site available for an arterial anastomosis. Under appropriate circumstances, this procedure would be an option for potential combined pancreas-kidney transplant recipients with severe calcific arterial disease.
Collapse
Affiliation(s)
- A Sugitani
- Department of Surgery, Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA
| | | | | | | | | |
Collapse
|
|
29
|
Schlenker E, Feldmeyer F, Hoster M, Rühle KH. [Effect of noninvasive ventilation on pulmonary artery pressure in patients with severe kyphoscoliosis]. MEDIZINISCHE KLINIK (MUNICH, GERMANY : 1983) 1997; 92 Suppl 1:40-4. [PMID: 9235474 DOI: 10.1007/bf03041809] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Many studies have shown, that non invasive ventilation via nasal access can normalize alveolar ventilation for individuals due to kyphoscoliotic deformity. The purpose of this study was to evaluate the effect of nasal IPPV on the pulmonary artery pressures (Pam) and the sleep efficiency of kyphoscoliotic individuals. PATIENTS AND METHODS Five patients were studied (4 men, 1 woman; age 50.5 +/- 6.9 years): all patients showed hypoxemia and hypercapnia before therapy. We followed the patients about 6 months under NIPPV. We measured PImax, PaO2, PaCO2, Pam before and after 6 months with NIPPV. RESULTS PImax increased from 4.9 +/- 2.3 kPa to 6.5 +/- 1.3 kPa, PaO2 increased from 46.2 +/- 12.2 mmHg to 56.7 +/- 8.5 mmHg. PaCO2 decreased from 53.0 +/- 3.2 to 45.3 +/- 3.2. Pam decreased from 41.0 +/- 15.1 to 23.2 +/- 10.7 in 6 months of NIPPV. Total sleep time increased from 222 +/- 52 min to 326 +/- 43 min with NIPPV. CONCLUSION Similar to O2 long-term therapy in patients with COPD. NIPPV delivers in patients with kyphoscoliotic deformity a significant reduction of pulmonary artery pressure and increase of sleep quality.
Collapse
|
|
30
|
Allen RD, Al-Harbi IS, Morris JG, Clouston PD, O'Connell PJ, Chapman JR, Nankivell BJ. Diabetic neuropathy after pancreas transplantation: determinants of recovery. Transplantation 1997; 63:830-8. [PMID: 9089222 DOI: 10.1097/00007890-199703270-00007] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.
Collapse
Affiliation(s)
- R D Allen
- Department of Neurology, Westmead Hospital, Sydney, Australia
| | | | | | | | | | | | | |
Collapse
|
|
31
|
Bruce DS, Newell KA, Josephson MA, Woodle ES, Piper JB, Millis JM, Seaman DS, Carnrike CL, Huss E, Thistlethwaite JR. Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year. Transplantation 1996; 62:451-6. [PMID: 8781609 DOI: 10.1097/00007890-199608270-00005] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.
Collapse
Affiliation(s)
- D S Bruce
- Department of Surgery, University of Chicago, Illinois 60637, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Abstract
Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The usual pattern is a distal symmetrical sensory polyneuropathy, associated with autonomic disturbances. Less often, diabetes is responsible for a focal or multifocal neuropathy affecting cranial nerves, especially oculomotor nerves, and roots and nerves innervating proximal muscles of the lower limbs. Metabolic abnormalities due to hyperglycaemia, lack of insulin and their consequences and ischaemic phenomena secondary to diabetic microangiopathy account for nerve lesions.
Collapse
Affiliation(s)
- G Said
- Service de Neurologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
| |
Collapse
|
|
33
|
Sutherland DE, Gruessner RW, Gores PF, Brayman K, Wahoff D, Gruessner A. Pancreas transplantation: an update. DIABETES/METABOLISM REVIEWS 1995; 11:337-363. [PMID: 8718495 DOI: 10.1002/dmr.5610110404] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- D E Sutherland
- University of Minnesota Hospital and Clinic, Minneapolis 55455, USA
| | | | | | | | | | | |
Collapse
|
|
34
|
Abstract
Vascularized pancreas transplantation has assumed an increasing role in the treatment of diabetes mellitus. Through 1994, over 6000 pancreas transplants had been performed worldwide, with over 80% being combined pancreas-kidney transplants. Overall 1-year patient survival exceeds 90% and graft survival (complete insulin independence) exceeds 70%. Although successful pancreas transplantation achieves euglycemia and complete insulin independence, this occurs at the expense of hyperinsulinemia and chronic immunosuppression. The net effect of these changes on diabetic complications in the long term remains to be determined. In the short term, improvement in the quality of life and possible prevention of further morbidity associated with diabetes makes pancreas transplantation an important therapeutic option, particularly when combined with a kidney transplant, in appropriately selected diabetic patients.
Collapse
Affiliation(s)
- R J Stratta
- Department of Surgery, University of Nebraska Medical Center, Omaha 68198-3280, USA
| | | | | | | |
Collapse
|
|
35
|
Stratta RJ, Taylor RJ, Larsen JL, Cushing K. Pancreas transplantation. INTERNATIONAL JOURNAL OF PANCREATOLOGY : OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION OF PANCREATOLOGY 1995; 17:1-13. [PMID: 8568329 DOI: 10.1007/bf02788353] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Affiliation(s)
- R J Stratta
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | | | | | | |
Collapse
|
|
36
|
van Gerven JM, Tjon-A-Tsien AM. The efficacy of aldose reductase inhibitors in the management of diabetic complications. Comparison with intensive insulin treatment and pancreatic transplantation. Drugs Aging 1995; 6:9-28. [PMID: 7696781 DOI: 10.2165/00002512-199506010-00002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Recently, aldose reductase inhibitors (ARIs) have been registered in several countries for the improvement of glycaemic control. However, their efficacy is still controversial. ARIs inhibit the enhanced flux of glucose through the polyol pathway. As such, they can never be more effective than normoglycaemia, and so their potential benefits and limitations should be considered relative to the effects of prolonged euglycaemia. The clinical effects of ARIs can be put into perspective by assessing the effects of improved glycaemic control attained in randomised trials of intensive insulin treatment [such as the Diabetes Control and Complications Trial (DCCT)] and after pancreatic transplantation. Although direct comparison of these 3 interventions is hampered by differences in patient populations, duration and methods of follow-up and in the potency of ARIs, the effects of these 3 metabolic interventions and their course in time appear remarkably similar. For neuropathy, all 3 interventions induce an increase in average motor nerve conduction velocity of approximately 1 m/sec during the first months of treatment. At the same time, improvement of painful symptoms may occur. These changes probably largely represent a metabolic amelioration of the condition of the nerves. Around the second year of treatment with all 3 forms of metabolic improvement, an acceleration of nerve conduction of a similar magnitude occurs, with signs of structural nerve regeneration and some sensory recuperation. Experience with ARIs in nephropathy is still limited, but similar improvements in glomerular filtration rate and, less consistently, in urinary albumin excretion were found during short term normoglycaemia produced by all 3 forms of treatment. Comparison of a small number of studies, however, shows differences between intensive insulin regimens, pancreatic transplantation and ARIs in effects on retinopathy. Retinopathy often temporarily deteriorates in the early phases of improved glycaemic control, but this is not noted with ARIs. New microaneurysm formation was slightly reduced in a single long term study with the ARI sorbinil, but the preventive effects on the overall levels of retinopathy seemed less strong than in normoglycaemia trials of similar duration. However, the pharmacodynamic effects on inhibiting the polyol pathway differ among ARIs, and the half-life of the inhibiting effect of sorbinil may have been too short for a complete reduction of polyol pathway activity. The trials of prolonged intensive insulin therapy and pancreatic transplantation have demonstrated that very strict metabolic control must be maintained continuously for many years before a significant reduction of complications can be demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)
Collapse
Affiliation(s)
- J M van Gerven
- Centre for Human Drug Research, University Hospital, Leiden, The Netherlands
| | | |
Collapse
|
|
37
|
Abstract
Over the last thirty years, organ transplantation has become a practical treatment option for many otherwise fatal diseases. New immunosuppressive agents, advances in tissue matching, and improvements in surgical technique have increased both the number and type of transplants performed. Kidney, bone marrow, heart, lung, liver, and pancreas transplants are now used regularly in the treatment of end-stage disease. However, these advances have come at a price. Transplant recipients are subject to numerous complications, many of which involve the nervous system. Depending on the type of organ transplanted, 30 to 60% of transplant recipients experience neurological problems. Most neurological complications, especially those related to immunosuppression, are common to all transplant types; other complications are associated predominantly with specific transplant types. This report reviews the general categories of neurological complications as well as the specific problems associated with each kind of transplant.
Collapse
Affiliation(s)
- R A Patchell
- Department of Neurology, University of Kentucky Medical Center, Lexington 40536-0084
| |
Collapse
|