title: The prognostic values of caveolin-1 immunoreactivity in peritubular capillaries in patients with kidney transplantation.
abstract: The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection (CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts (ENDATs). We previously showed that the ENDAT caveolin-1 (CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients. Ninety-eight kidney transplant recipients were included in this study. The prognostic value of CAV-1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV-1 and pathologische Anatomie Leiden endothelium (PAL-E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV-1/PAL-E<50% and CAV-1/PAL-E≥50%. Kaplan-Meier curves showed that CAV-1/PAL-E≥50% patients had a significantly worse prognosis than that of CAV-1/PAL-E<50% patients (log-rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log-rank; P=.345), whereas in a multivariate Cox regression analysis, CAV-1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV-1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakada
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. izumi26@jikei.ac.jp.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamamoto
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Mafune
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Katsumata
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Katsuma
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kawabe
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yudo
authors.initials: Y
authors.lastname: Tanno
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ohkido
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuboi
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.|Department of Internal Medicine, Atsugi City Hospital, Kanagawa, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Okumi
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoo
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000276:immunology / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C495540:CAV1 protein, human; D051242:Caveolin 1
keywords: caveolae; caveolin-1; chronic active antibody-mediated rejection; kidney graft survival; transplant glomerulopathy