University of Wisconsin Solution with Trypsin Inhibitor Pefabloc Improves Survival of Viable Human and Primate Impure Islets During Storage

Background. Recent studies suggest that impure islets (islets which have not been isolated from exocrine tissue and other parts of the pancreas) have great potential for successful transplantation. The evidence that supports this view includes findings that embedded islets (islets surrounded by exocrine tissue) undergo less apoptosis, peripancreatic lymph nodes prevent recurrence of IDDM (insulin dependent diabetes mellitus), and that islet yields and insulin content decrease during the purification process. Improved protocols have also been developed to prevent allorejection of impure islets. Despite these promising results, the storage of impure islets remains difficult, and was a method sought to decrease storage losses. Methods. Storage methods of impure human and non-human primate islets were compared, using either culture media or University of Wisconsin solution (UW). The effects of trypsin inhibition using Pefabloc (Roche Molecular Biochemicals, Indianapolis, IN) during storage period were also examined. Results. Low temperature and inhibition of trypsin activity during storage of impure islets improved both islet yield and viability. It was found that using UW solution and trypsin inhibition allowed perfect preservation of viable impure islets up to 48 h. A functional assay by glucose stimulation test showed these impure islet responded to glucose stimulation after 24 h. Conclusion. The benefits of storing impure islets using UW solution and Pefabloc at low temperature have been established. This improved method of preserving impure islets makes this model of transplantation even more viable

University of Wisconsin Solution with Trypsin Inhibitor Pefabloc Improves Survival of Viable Human and Primate Impure Islets During Storage

Background. Recent studies suggest that impure islets (islets which have not been isolated from exocrine tissue and other parts of the pancreas) have great potential for successful transplantation. The evidence that supports this view includes findings that embedded islets (islets surrounded by exocrine tissue) undergo less apoptosis, peripancreatic lymph nodes prevent recurrence of IDDM (insulin dependent diabetes mellitus), and that islet yields and insulin content decrease during the purification process. Improved protocols have also been developed to prevent allorejection of impure islets. Despite these promising results, the storage of impure islets remains difficult, and was a method sought to decrease storage losses. Methods. Storage methods of impure human and non-human primate islets were compared, using either culture media or University of Wisconsin solution (UW). The effects of trypsin inhibition using Pefabloc (Roche Molecular Biochemicals, Indianapolis, IN) during storage period were also examined. Results. Low temperature and inhibition of trypsin activity during storage of impure islets improved both islet yield and viability. It was found that using UW solution and trypsin inhibition allowed perfect preservation of viable impure islets up to 48 h. A functional assay by glucose stimulation test showed these impure islet responded to glucose stimulation after 24 h. Conclusion. The benefits of storing impure islets using UW solution and Pefabloc at low temperature have been established. This improved method of preserving impure islets makes this model of transplantation even more viable

Successful Urgent Transplantation of an Adult Kidney into a Child with Inferior Vena Cava Thrombosis

Poor venous drainage options following inferior vena cava (IVC) thrombosis have been considered to complicate or preclude renal transplantation of adult kidneys into pediatric patients. We describe urgent renal transplantation in a 5-year-old (15.3 kg) male with IVC thrombosis using an adult living donor. Preoperative magnetic resonance venography revealed a patent infrahepatic/suprarenal vena cava and portal system. In surgery, the right liver lobe was mobilized sufficiently to anastomose the graft renal vein to the native IVC at the confluence of the native left renal vein and proximal vena cava. Graft function has remained excellent with serum creatinine of 0.5 mg/dL at 36 months. IVC thrombosis need not preclude successful transplantation of adult-sized kidneys into children

Albuminuria after Renal Transplantation: Maintenance with Sirolimus/Low-Dose Tacrolimus vs. Mycophenolate Mofetil/High-Dose Tacrolimus

Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine–tryptophan–ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications

Acute Transverse Myelitis and Paralysis in a Kidney–Pancreas Recipient

Acute transverse myelitis (ATM), a group of neurologic disorders with an incidence of one to four cases per million people per year, is characterized by focal inflammation of the spinal cord resulting in sensory, motor, and autonomic dysfunction. ATM may be caused by infection, spinal cord infarction, pre-existing inflammatory disease (e.g., SLE) or de novo autoimmunity (idiopathic)

Acute Transverse Myelitis and Paralysis in a Kidney–Pancreas Recipient

Acute transverse myelitis (ATM), a group of neurologic disorders with an incidence of one to four cases per million people per year, is characterized by focal inflammation of the spinal cord resulting in sensory, motor, and autonomic dysfunction. ATM may be caused by infection, spinal cord infarction, pre-existing inflammatory disease (e.g., SLE) or de novo autoimmunity (idiopathic)

Acute Transverse Myelitis and Paralysis in a Kidney–Pancreas Recipient

Acute transverse myelitis (ATM), a group of neurologic disorders with an incidence of one to four cases per million people per year, is characterized by focal inflammation of the spinal cord resulting in sensory, motor, and autonomic dysfunction. ATM may be caused by infection, spinal cord infarction, pre-existing inflammatory disease (e.g., SLE) or de novo autoimmunity (idiopathic)