Long-term outcomes of patients with end-stage kidney disease due to membranous nephropathy: A cohort study using the Australia and New Zealand Dialysis and Transplant Registry

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Abstract

Background

Clinical outcomes of patients with end-stage kidney disease (ESKD) secondary to membranous nephropathy (MN) have not been well described. This study aimed to evaluate patient and/or allograft outcomes of dialysis or kidney transplantation in patients with ESKD secondary to MN.

Material and methods

All adult patients with ESKD commencing renal replacement therapy in Australia and New Zealand from January 1998 to December 2010 were extracted retrospectively from ANZDATA registry on 31 ^st December 2013. Outcomes of MN were compared to other causes of ESKD. In a secondary analysis, outcomes of MN were compared to all patients with ESKD due to other forms of glomerulonephritis.

Results

Of 32,788 included patients, 417 (1.3%) had MN. Compared to other causes of ESKD, MN experienced lower mortality on dialysis (adjusted hazard ratio [aHR] 0.79, 95% CI 0.68–0.92, p = 0.002) and following kidney transplantation (aHR 0.57, 95% CI 0.33–0.97, p = 0.04), had a higher risk of death-censored kidney allograft failure (aHR 1.55, 95% CI: 1.00–2.41, p = 0.05) but comparable risk of overall kidney allograft failure (aHR 1.35, 95% CI 0.91–2.01, p = 0.13). Similar results were obtained using competing-risk regression analyses. MN patients were significantly more likely to receive a kidney transplant (aHR 1.38, 95% CI 1.16–1.63, p<0.001) and to experience primary kidney disease recurrence in the allograft (aHR 4.92, 95% CI 3.02–8.01, p<0.001). Compared to other forms of glomerulonephritis, MN experienced comparable dialysis and transplant patient survival, but higher rates of kidney transplantation, primary renal disease recurrence and death-censored allograft failure.

Conclusion

MN was associated with superior survival on dialysis and following kidney transplantation compared to patients with other causes of ESKD, and comparable patient survival compared to patients with other forms of glomerulonephritis. However, patients with MN exhibited a higher rate of death-censored allograft loss as a result of primary kidney disease recurrence.

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Most cited references 37

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Primary Membranous Nephropathy.

William G. Couser (2017)

Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.

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Pathophysiological advances in membranous nephropathy: time for a shift in patient's care.

Pierre Ronco, Hanna Debiec (2015)

Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insufficient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specific to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identified as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A2 receptor (PLA2R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA2R antibodies in serum and detection of PLA2R antigen in glomerular deposits can now be done routinely. Anti-PLA2R antibodies have high specificity (close to 100%), sensitivity (70-80%), and predictive value. PLA2R detection in immune deposits allows for retrospective diagnosis of PLA2R-related membranous nephropathy in archival kidney biopsies. These tests already have a major effect on diagnosis and monitoring of treatment, including after transplantation.

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Risk of renal allograft loss from recurrent glomerulonephritis.

David Atkins, E Briganti, Clayton J. McNeil … (2002)

Recurrent glomerulonephritis is a known cause of renal allograft loss; however, the incidence of this complication is poorly defined. We determined the incidence, timing, and relative importance of allograft loss due to the recurrence of glomerulonephritis. A total of 1505 patients with biopsy-proved glomerulonephritis received a primary renal transplant in Australia from 1988 through 1997. Recurrence was confirmed by renal biopsy. The Kaplan-Meier method was used to estimate the 10-year incidence of allograft failure due to recurrent glomerulonephritis, and this incidence was compared with the incidence of acute rejection, chronic rejection, and death with a functioning allograft. Characteristics of the recipients and donors were examined as potential predictors of recurrence. Allograft loss due to the recurrence of glomerulonephritis occurred in 52 recipients, with a 10-year incidence of 8.4 percent (95 percent confidence interval, 5.9 to 12.0). The type of glomerulonephritis, the sex of the recipient, and the peak level of panel-reactive antibodies were independent predictors of the risk of recurrence. Recurrence was the third most frequent cause of allograft loss at 10 years, after chronic rejection and death with a functioning allograft. Despite the effect of recurrence, the overall 10-year incidence of allograft loss was similar among transplant recipients with biopsy-proved glomerulonephritis and among those with other causes of renal failure (45.4 percent [95 percent confidence interval, 40.9 to 50.2] vs. 45.8 percent [95 percent confidence interval, 42.3 to 49.3], P=0.09). Recurrence is an important cause of allograft loss for those with renal failure due to glomerulonephritis. No risk factors for recurrence were identified that warrant altering the approach to transplantation. However, accurate estimates of risk can now be provided to potential recipients of renal allografts.

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Author and article information

Contributors

Wen-ling Yang:

ORCID: http://orcid.org/0000-0002-6348-7747

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing

Bhadran Bose: Role: Formal analysisRole: InvestigationRole: Writing – review & editing

Lei Zhang: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing

Megan Mcstea: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – review & editing

Yeoungjee Cho: Role: InvestigationRole: Writing – review & editing

Magid Fahim: Role: InvestigationRole: Writing – review & editing

Carmel M. Hawley: Role: SupervisionRole: Writing – review & editing

Elaine M. Pascoe:

ORCID: http://orcid.org/0000-0003-1653-5803

Role: Writing – review & editing

David W. Johnson:

ORCID: http://orcid.org/0000-0001-5491-3460

Zhanjun Jia: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 23 August 2019

Publication date Collection: 2019

Volume: 14

Issue: 8

Electronic Location Identifier: e0221531

Affiliations

[1 ] Department of Nephrology, Peking University Third Hospital, Beijing, China

[2 ] Division of Nephrology, Princess Alexandra Hospital, Brisbane, Australia

[3 ] Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, Adelaide, Australia

[4 ] Australasian Kidney Trials Network, The University of Queensland, Queensland, Australia

[5 ] Department of Nephrology, Nepean Hospital, Kingswood, Australia

[6 ] Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

[7 ] Translational Research Institute, Brisbane, Australia

University of Utah School of Medicine, UNITED STATES

Author notes

Competing Interests: DJ has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare ( https://www.baxterhealthcare.com.au), Fresenius Medical Care ( https://www.fmc-au.com/) and Amgen ( www.amgen.com.au) Australia Pty Ltd. He is supported by a National Health and Medical Research Council (NHMRC) Practitioner Fellowship. YC has received research grants from Baxter Healthcare ( https://www.baxterhealthcare.com.au) and Fresenius Medical Care ( https://www.fmc-au.com/). She is supported by a NHMRC early career fellowship. CH has received research grants form Baxter Health ( https://www.baxterhealthcare.com.au), Fresenius Medical Care ( https://www.fmc-au.com/) and Amgen ( www.amgen.com.au). All others have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

‡ Wen-ling Yang and Bhadran Bose are equal first authors on this work.

* E-mail: yanglw2003@ 123456hotmail.com

Author information

Wen-ling Yang http://orcid.org/0000-0002-6348-7747

Elaine M. Pascoe http://orcid.org/0000-0003-1653-5803

David W. Johnson http://orcid.org/0000-0001-5491-3460

Article

Publisher ID: PONE-D-19-10701

DOI: 10.1371/journal.pone.0221531

PMC ID: 6707602

PubMed ID: 31442267

SO-VID: 58a2ac4a-55f9-488a-96b7-26e30747da09

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 22 April 2019

Date accepted : 8 August 2019

Page count

Figures: 4, Tables: 2, Pages: 15

Funding

The author(s) received no specific funding for this work.

Custom metadata

Data Availability All relevant data are within the paper and its Supporting Information files.

Long-term outcomes of patients with end-stage kidney disease due to membranous nephropathy: A cohort study using the Australia and New Zealand Dialysis and Transplant Registry

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Abstract

Background

Material and methods

Results

Conclusion

Related collections

PLOS Climate

Most cited references 37

Primary Membranous Nephropathy.

Pathophysiological advances in membranous nephropathy: time for a shift in patient's care.

Risk of renal allograft loss from recurrent glomerulonephritis.

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Contributors

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