Philippe Klee1,2, Mirjam Dirlewanger3,4, Vanessa Lavallard5, Valerie A McLin6, Anne Mornand7, Nadine Pernin5, Laetitia-Marie Petit6, Paola M Soccal8, Barbara E Wildhaber9, Urs Zumsteg10, Jean-Louis Blouin11, Thierry Berney12, Valerie M Schwitzgebel3,4. 1. Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, University Hospitals of Geneva, Geneva, Switzerlandphilippe.klee@hcuge.ch. 2. Diabetes Center of the Faculty of Medicine, University of Geneva, Geneva, Switzerlandphilippe.klee@hcuge.ch. 3. Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, University Hospitals of Geneva, Geneva, Switzerland. 4. Diabetes Center of the Faculty of Medicine, University of Geneva, Geneva, Switzerland. 5. Cell Isolation and Transplantation Center, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 6. Division of Pediatric Gastroenterology, Department of Pediatrics, University Hospitals of Geneva, Geneva, Switzerland. 7. Pediatric Pneumology Unit, Department of Pediatrics, University Hospitals of Geneva, Geneva, Switzerland. 8. Service of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland. 9. Division of Pediatric Surgery, University Centre of Pediatric Surgery of Western Switzerland, University Hospitals of Geneva, Geneva, Switzerland. 10. Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, University of Basel Children's Hospital, Basel, Switzerland. 11. Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 12. Division of Transplantation, Department of Surgery, University Hospitals of Geneva, Geneva, Switzerland.
Abstract
BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is the most frequent extrapulmonary complication of cystic fibrosis (CF). METHODS: We report the first combined pancreatic islet-lung-liver transplantation in a 14-year-old adolescent. CFTR was analyzed by Sanger sequencing. Further genes were analyzed by high-throughput sequencing. RESULTS: The patient was diagnosed with CF at the age of 14 months. Nine years later, after diagnosis of CFRD, the patient's BMI and lung function began to decline. Bilateral lung transplantation with simultaneous liver transplantation was performed at the age of 14.5 years. The first islet transplantation (IT) was carried out 10 days later. Six months later, C-peptide secretion after arginine stimulation showed peak values of 371 pmol/L (vs. 569 pmol/L before IT) and insulin doses had slightly increased (1.40 vs. 1.11 units/kg/day before IT). A second IT was performed at the age of 15 years, a third at 16 years. Two years after the first IT, arginine-stimulated C-peptide secretion increased to 2,956 pmol/L and insulin doses could be reduced to 0.82 units/kg/day. HbA1c decreased from 7.3% (57.4 mmol/mol) to 5.9% (41.0 mmol/mol). CONCLUSION: IT following lung and liver transplantation, with injection of islets into a transplanted organ, is feasible. It improves C-peptide secretion, decreases insulin needs, and lowers HbA1c.
BACKGROUND:Cystic fibrosis-related diabetes (CFRD) is the most frequent extrapulmonary complication of cystic fibrosis (CF). METHODS: We report the first combined pancreatic islet-lung-liver transplantation in a 14-year-old adolescent. CFTR was analyzed by Sanger sequencing. Further genes were analyzed by high-throughput sequencing. RESULTS: The patient was diagnosed with CF at the age of 14 months. Nine years later, after diagnosis of CFRD, the patient's BMI and lung function began to decline. Bilateral lung transplantation with simultaneous liver transplantation was performed at the age of 14.5 years. The first islet transplantation (IT) was carried out 10 days later. Six months later, C-peptide secretion after arginine stimulation showed peak values of 371 pmol/L (vs. 569 pmol/L before IT) and insulin doses had slightly increased (1.40 vs. 1.11 units/kg/day before IT). A second IT was performed at the age of 15 years, a third at 16 years. Two years after the first IT, arginine-stimulated C-peptide secretion increased to 2,956 pmol/L and insulin doses could be reduced to 0.82 units/kg/day. HbA1c decreased from 7.3% (57.4 mmol/mol) to 5.9% (41.0 mmol/mol). CONCLUSION: IT following lung and liver transplantation, with injection of islets into a transplanted organ, is feasible. It improves C-peptide secretion, decreases insulin needs, and lowers HbA1c.
Authors: Thierry Berney; Axel Andres; Melena D Bellin; Eelco J P de Koning; Paul R V Johnson; Thomas W H Kay; Torbjörn Lundgren; Michael R Rickels; Hanne Scholz; Peter G Stock; Steve White Journal: Transpl Int Date: 2022-08-11 Impact factor: 3.842