title: APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair.
abstract: We report an occurrence of progressive loss of transplant function and ultimately transplant failure after living related kidney transplantation involving monozygotic twin brothers of Afro-Caribbean origin who were both heterozygous for the G1 and G2 kidney disease risk alleles in the APOL1 gene, which encodes apolipoprotein L-I. A 21-year-old man with end-stage kidney disease of unknown cause received a kidney from his brother, who was confirmed as a monozygotic twin by microsatellite analysis. Thirty months after transplantation, the patient presented with proteinuria and decreased estimated glomerular filtration rate; a biopsy of the transplant showed typical focal segmental glomerulosclerosis lesions. He received steroid therapy, but progressed to kidney failure 5 years later. The twin brother had normal kidney function without proteinuria at the time of transplantation; however, 7 years later, he was found to have decreased estimated glomerular filtration rate (40mL/min/1.73m(2)) and proteinuria (protein excretion of 2.5g/d). APOL1 genotyping revealed that both donor and recipient were heterozygous for the G1 and G2 alleles. This case is in stark contrast to the expected course of kidney transplantation in identical twins and suggests a role for APOL1 polymorphisms in both the donor and recipient.
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France. Electronic address: thomas.kofman@hmn.aphp.fr.
authors: Tomek
authors: T
authors: Kofman
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Vincent
authors: V
authors: Audard
authors: Université Paris Descartes, INSERM UMR-S 775, APHP, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire, Paris, France.
authors: Céline
authors: C
authors: Narjoz
authors: INSERM U983, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors: Olivier
authors: O
authors: Gribouval
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Marie
authors: M
authors: Matignon
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Claire
authors: C
authors: Leibler
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Dominique
authors: D
authors: Desvaux
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Philippe
authors: P
authors: Lang
authors: Service de Néphrologie et Transplantation, Hôpital Henri Mondor, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U955, Université Paris Est Créteil, APHP (Assistance Publique-Hôpitaux de Paris, Créteil), Créteil, France.
authors: Philippe
authors: P
authors: Grimbert
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D004200:Diseases in Twins; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D019520:Living Donors; D008297:Male; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: APOL1 polymorphism; African ancestry; focal segmental glomerulosclerosis (FSGS); kidney transplantation; living donor; monozygotic twin; renal disease; risk allele