Islet Transplantation Is Associated with Improvement of Renal Function among Uremic Patients with Type I Diabetes Mellitus and Kidney Transplants

Fiorina, Paolo; Folli, Franco; Zerbini, Gianpaolo; Maffi, Paola; Gremizzi, Chiara; Carlo, V. Di; Socci, C.; Bertuzzi, Federico; Kashgarian, Michael; Secchi, Antonio

doi:10.1097/01.asn.0000077339.20759.a3

Cited by 157 publications

(95 citation statements)

References 35 publications

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“…In patients who underwent simultaneous pancreas-kidney or islet-kidney transplantation, improved cumulative survival, kidney graft size, and function were reported in the group with a functioning pancreas or islets (9). Furthermore, insulin independence was not required for a positive effect on kidney function (8), supporting the EDIC finding that patients with type 1 diabetes with residual C-peptide function have a lower risk of diabetic nephropathy (2). The question of how to balance the risks and benefits of islet transplantation in regard to kidney function is still unanswered.…”

Section: Diabetes Who Received Islet Transplantation Alone and The Edmentioning

confidence: 74%

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Kidney Function After Islet Transplant Alone in Type 1 Diabetes

et al. 2007

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OBJECTIVE -Islet transplantation alone is an alternative for the replacement of pancreatic endocrine function in patients with type 1 diabetes. The aim of our study was to assess the impact of the Edmonton immunosuppressive protocol (tacrolimus-sirolimus association) on kidney function. RESEARCH DESIGN AND METHODS-Nineteen patients with type 1 diabetes and metabolic instability received islet transplantation alone and immunosuppressive therapy according to the Edmonton protocol. Serum creatinine (sCr), creatinine clearance (CrCl), and 24-h urinary protein excretion (UPE) were assessed at baseline and during a follow-up of 339 patientmonths.RESULTS -After islet transplantation we observed 1) sCr within the normal range in all but two patients in whom sCr increased immediately after islet transplantation, and despite withdrawal of immunosuppression, patients progressed to end-stage renal disease (ESRD); 2) CrCl remained within the normal range for those patients who had normal baseline values and decreased, progressing to ESRD in two patients with a decreased baseline CrCl; and 3) 24-h UPE worsened (Ͼ300 mg/24 h) in four patients. In the two patients who progressed to ESRD, the worsening of 24-h UPE occurred immediately after islet transplantation. In one patient 24-h UPE worsening occurred at 18 months, and, after withdrawal of immunosuppression, it returned to the normal range. In another patient 24-h UPE increased at 24 months and remained stable while immunosuppression was continued.CONCLUSIONS -In type 1 diabetic patients receiving islet transplantation alone, the association of tacrolimus and sirolimus should be used only in patients with normal kidney function. Alternative options for immunosuppressive treatment should be considered for patients with even a mild decrease of kidney function. Diabetes Care 30:1150 -155, 2007T he Diabetes Control and Complications Trial has shown that in patients with type 1 diabetes, intensive diabetes treatment reduces incidence and delays progression of long-term complications (1). The Epidemiology of Diabetes Intervention and Complications (EDIC) study, a follow-up of the original Diabetes Control and Complications Trial cohort, has shown a sustained effect of intensive diabetes treatment on the development and progression of nephropathy and macrovascular disease (2). Furthermore, the EDIC study has shown that patients with type 1 diabetes with some endogenous Cpeptide reserve have a lower risk of progression of retinopathy and neuropathy (2). However, the benefits of intensive diabetes treatment come with the price of severe hypoglycemia and increased body weight (1).Several studies have reported a high rate of insulin independence and normalization of blood glucose and A1C levels after either pancreas or islet transplantation (3-7). In patients with type 1 diabetes, pancreas or islet transplantation has improved kidney graft survival (8,9), whereas the positive impact of pancreas transplantation on the native kidney has been counterbalanced by the nephrotoxicity of immun...

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Section: Diabetes Who Received Islet Transplantation Alone and The Edmentioning

confidence: 74%

“…In patients with type 1 diabetes, pancreas or islet transplantation has improved kidney graft survival (8,9), whereas the positive impact of pancreas transplantation on the native kidney has been counterbalanced by the nephrotoxicity of immunosuppressants, namely calcineurin inhibitors (10,11).…”

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confidence: 99%

Kidney Function After Islet Transplant Alone in Type 1 Diabetes

et al. 2007

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“…Furthermore, it positively correlated with an increased rate of urine flow, which was observed in the DM animals in this study (Fiorina et al. 2003; Song et al. 2003; Castiglione et al.…”

Section: Discussionmentioning

confidence: 99%

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

et al. 2017

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Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC‐5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24‐h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC‐5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real‐time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC‐5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low‐molecular‐weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats.

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“…Despite the promises, the only existing, feasible therapeutic alternatives to insulin injections for type 1 diabetic patients are pancreas and islet allo-transplantations from deceased or living organ donors [4][5][6][7]. Encouraging achievements in the field of pancreas and islet transplantation, at least in a selected cohort of adult type 1 diabetic patients, have been obtained in recent years [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Suitability of human juvenile pancreatic islets for clinical use

et al. 2006

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Aims/hypothesis The limited availability of deceased donor pancreases suitable for pancreas and islet transplantation calls for a broader utilisation of donor tissue for transplantation purposes. Young donors, representing, fortunately, a minor but significant pool of individuals, have been largely under-employed, mainly because of anatomical and functional incompatibilities with potential recipients. For islet transplantation, the isolation of pancreatic islets from young donors rarely occurs, because of technical problems. As a result of the peculiar characteristics of young donor pancreases, the standard isolation procedure does not allow efficient separation of the islets from the surrounding exocrine tissue, and favours the generation of mantled islets. Nonetheless, young donor islets offer high qualitative and clinically appealing characteristics. Subjects and methods We standardised a modified methodology to obtain purified and mantle-free human islets from young donors. This method principally involves efficient delivery of isolation enzyme with reduced mechanical disruption of the pancreas combined with additional filtration steps. Results We were able to obtain purified and mantle-free human islets from donors as young as 6 months of age with good morphological and functional properties. The good qualitative characteristics of the islets, evidenced in vitro, were proven in vivo, as they were qualitatively superior to islets of older donors in transplantation studies. Conclusions/interpretation This study justifies the utilisation of islets derived from young donors for islet transplantation.

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Islet Transplantation Is Associated with Improvement of Renal Function among Uremic Patients with Type I Diabetes Mellitus and Kidney Transplants

Cited by 157 publications

References 35 publications

Kidney Function After Islet Transplant Alone in Type 1 Diabetes

Kidney Function After Islet Transplant Alone in Type 1 Diabetes

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

Suitability of human juvenile pancreatic islets for clinical use

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