title: Acute kidney transplant rejection mediated by angiotensin II type 1 receptor antibodies in a pediatric hyperimmune patient.
abstract: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome.
  
  
  
  We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d. Test results were negative for donor-specific antibodies against human leukocyte antigens (HLA-DSA) and MHC class I-related chain A (MICA) but positive for AT1R-Ab. Retrospective testing of the sera collected during the first kidney transplant was also positive for AT1R-Ab. We therefore hypothesized that the failure of the first transplant was secondary to the same cause. Losartan was immediately introduced into the therapeutic regimen, and the patient showed an excellent clinical and histological recovery.
  
  
  
  Testing for AT1R-Ab in any hypertensive patient with acute rejection who tests negative or weakly positive for C4d and negative for HLA-DSA and who is refractory to therapy is highly advisable. Pre-transplant AT1R-Ab may be indicative of the outcome in patients whose first transplant failed. Prompt initiation of treatment with losartan-immediately after transplantation in patients with pre-existing AT1R-Ab-should be encouraged.
authors.affiliation: Nephrology Unit, Department of Pediatrics, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy. isabella.guzzo@opbg.net.
authors.forename: Isabella
authors.identifier: 0000-0003-4960-3083
authors.initials: I
authors.lastname: Guzzo
authors.affiliation: Nephrology Unit, Department of Pediatrics, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Morolli
authors.affiliation: Pathology Unit, Department of Laboratories, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Francesca Diomedi
authors.initials: FD
authors.lastname: Camassei
authors.affiliation: National Council of Researches, IFT Unit of Rome S. Camillo Hospital - Regional Transplant Center Lazio, S. Camillo Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Piazza
authors.affiliation: National Council of Researches, IFT Unit of Rome S. Camillo Hospital - Regional Transplant Center Lazio, S. Camillo Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Poggi
authors.affiliation: Nephrology Unit, Department of Pediatrics, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dello Strologo
mesh_terms: D000293:Adolescent; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D056724:Immunity, Humoral; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan
keywords: AT1R-Ab; Acute rejection; HLA-DSA; Kidney transplant