Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal Antibodies

El-Zoghby, Ziad M.; Grande, Joseph P.; Fraile, Miguel; Norby, Suzanne M.; Fervenza, Fernando C.; Cosio, Fernando G.

doi:10.1111/j.1600-6143.2009.02851.x

Cited by 100 publications

(106 citation statements)

References 26 publications

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“…PVAN, poor allograft quality) may result in progressive deterioration of histology and graft failure months to years later (10). Similarly, GN and cAMR diagnosed at 1 year are often subclinical but cause late graft failure (29,9). Of interest, early alloimmune events not mediated by antibodies may trigger de novo DSA formation and cAMR (3,30).…”

Section: Discussionmentioning

confidence: 99%

Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

Cosio

Ters

Cornell

et al. 2016

American Journal of Transplantation

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Allograft histology 1 year posttransplant is an independent correlate to long-term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999-2010, followed for 93.4 AE 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio .00], p < 0.0001) or glomerulonephritis .0], p < 0.0001). Compared to unfavorable, in grafts with favorable histology, failure was most commonly due to death (42% vs. 70%, p < 0.0001) and less commonly due to alloimmune causes (27% vs. 10%, p < 0.0001). In 80% of cases, favorable histology persisted at 2 years. However, de novo 2-year unfavorable histology (15.3%) or glomerulonephritis (4.7%) related to reduced survival. The proportion of favorable grafts increased during this period (odds ratio ¼ 0.920 [0.871-0.972], p ¼ 0.003, per year) related to fewer DGF, rejections, polyoma-associated nephropathy (PVAN), and better function. Graft survival also improved ], p ¼ 0.015) related to better histology and function. Evolution of graft histologic early posttransplant relate to long-term survival. Avoiding risk factors associated with unfavorable histology relates to improved histology and graft survival.

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Section: Discussionmentioning

confidence: 99%

Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

Cosio

Ters

Cornell

et al. 2016

American Journal of Transplantation

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“…In such cases, genetic differences in the expression and/or conformation of PLA 2 R within the allograft may be unfavorable for in situ immune complex formation or the induction therapy and transplant immunosuppression may be sufficient to achieve immunological remission. In those with persistence or re-development of anti-PLA 2 R for longer durations, full-blown recurrent MN can occur, often requiring additional immunosuppressive agents such as rituximab (82,83).…”

Section: Recurrent Mnmentioning

confidence: 99%

Membranous nephropathy: from models to man

Beck¹,

Salant²

2014

J. Clin. Invest.

149

138

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As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A 2 receptor 1 (PLA 2 R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA 2 R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.

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“…Rituximab, a chimeric anti-CD20 monoclonal antibody used for anti-B cell therapy, has recently been investigated as a promis-ing agent for the treatment of membranous nephropathy (MN) in the native kidney and for recurrent MN in the allograft. [2][3][4][5][6][7] Treatment response has been assessed by the attainment of a complete or partial clinical remission, whereas other laboratory parameters have not been useful in monitoring therapy.…”

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confidence: 99%

Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy

Beck

Fervenza

Beck

et al. 2011

Journal of the American Society of Nephrology

412

315

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Autoantibodies to the M-type phospholipase A 2 receptor (PLA 2 R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA 2 R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA 2 R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA 2 R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA 2 R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA 2 R. In summary, measuring anti-PLA 2 R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

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Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal Antibodies

Cited by 100 publications

References 26 publications

Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

Membranous nephropathy: from models to man

Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy

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