TY - JOUR
T1 - Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy
T2 - A Multicenter Case Series
AU - Batal, Ibrahim
AU - Vasilescu, Elena Rodica
AU - Dadhania, Darshana M.
AU - Adel, Aidoud Abderrahmane
AU - Husain, S. Ali
AU - Avasare, Rupali
AU - Serban, Geo
AU - Santoriello, Dominick
AU - Khairallah, Pascale
AU - Patel, Ankita
AU - Moritz, Michael J.
AU - Latulippe, Eva
AU - Riopel, Julie
AU - Khallout, Karim
AU - Swanson, Sidney J.
AU - Bomback, Andrew S.
AU - Mohan, Sumit
AU - Ratner, Lloyd
AU - Radhakrishnan, Jai
AU - Cohen, David J.
AU - Appel, Gerald B.
AU - Stokes, Michael B.
AU - Markowitz, Glen S.
AU - Seshan, Surya V.
AU - De Serres, Sacha A.
AU - Andeen, Nicole
AU - Loupy, Alexandre
AU - Kiryluk, Krzysztof
AU - D'Agati, Vivette D.
N1 - Funding Information:
Ibrahim Batal, MD, Elena-Rodica Vasilescu, MD, Darshana M. Dadhania, MD, Aidoud Abderrahmane Adel, MD, S. Ali Husain, MD, Rupali Avasare, MD, Geo Serban, PhD, Dominick Santoriello, MD, Pascale Khairallah, MD, Ankita Patel, MD, Michael J. Moritz, MD, Eva Latulippe, MD, Julie Riopel, MD, Karim Khallout, PhD, Sidney J. Swanson, MD, Andrew S. Bomback, MD, Sumit Mohan, MD, Lloyd Ratner, MD, Jai Radhakrishnan, MD, David J. Cohen, MD, Gerald B. Appel, MD, Michael B. Stokes, MD, Glen S. Markowitz, MD, Surya V. Seshan, MB, Sacha A. De Serres, MD, Nicole Andeen, MD, Alexandre Loupy, MD, Krzysztof Kiryluk, MD, and Vivette D. D'Agati, MD. Research idea and study design: IB, KKiryluk, VDD; data acquisition: IB, DS, EL, JRiopel, JRadhakrishnan, MBS, GSM, SVS, NA, ERV, PK, DMD, AAA, SAH, RA, GS, AP, MJM, ASB, SM, KKiryluk, KKhallout, LR, DJC, GBA, SADS, SJS, AL; data analysis/interpretation: IB, KKiryluk, VDD, AL, SADS, NA, DMD, SVS; statistical analysis: IB, SAH, SM. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author's own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Dr Batal is supported by a grant from the American Society of Transplantation Research Network. Dr Kiryluk is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant numbers RC2-DK116690 and R01-DK105124. Dr Mohan is supported by the National Institutes of Health (NIDDK/National Institute on Minority Health and Health Disparities/National Institute of Allergy and Infectious Diseases; R01 DK114893 and U01 DK116066). Dr Husain is supported by a Young Investigator Award from the National Kidney Foundation. The funders and the authors’ institutions had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. The authors declare that they have no relevant financial interests. We thank Dr David J. Salant and Megan Troxell for valuable insights and Yuancheng Wang, Patricia Maldonado, Hope Dzameshie, and Maria Lourdes Diaz Belvis of CUIMC and Lori Fletcher from OHSU for excellent technical assistance. Received August 28, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form January 7, 2020. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
Dr Batal is supported by a grant from the American Society of Transplantation Research Network. Dr Kiryluk is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant numbers RC2-DK116690 and R01-DK105124 . Dr Mohan is supported by the National Institutes of Health ( NIDDK / National Institute on Minority Health and Health Disparities / National Institute of Allergy and Infectious Diseases ; R01 DK114893 and U01 DK116066 ). Dr Husain is supported by a Young Investigator Award from the National Kidney Foundation . The funders and the authors’ institutions had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
Publisher Copyright:
© 2020 National Kidney Foundation, Inc.
PY - 2020/9
Y1 - 2020/9
N2 - Rationale & Objectives: Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood. Study Design: Multicenter case series. Setting & Participants: We included 77 patients from 5 North American and European medical centers with post–kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls. Findings: Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence. Limitations: Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies. Conclusions: De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.
AB - Rationale & Objectives: Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood. Study Design: Multicenter case series. Setting & Participants: We included 77 patients from 5 North American and European medical centers with post–kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls. Findings: Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence. Limitations: Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies. Conclusions: De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.
KW - HLA
KW - HLA-A3
KW - Membranous nephropathy (MN)
KW - allograft
KW - allograft biopsy
KW - allograft survival
KW - antibody-mediated rejection (AMR)
KW - case series
KW - de novo glomerulonephritis
KW - humoral alloimmunity
KW - pathology
KW - phospholipase A receptor (PLAR)
KW - recurrent glomerulonephritis
KW - renal transplantation
KW - steroid-free immunosuppression
UR - http://www.scopus.com/inward/record.url?scp=85083827580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083827580&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2020.01.009
DO - 10.1053/j.ajkd.2020.01.009
M3 - Article
C2 - 32359820
AN - SCOPUS:85083827580
SN - 0272-6386
VL - 76
SP - 374
EP - 383
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -