Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
Autoři:
Maida Mahmud aff001; Hans O. Pinnschmidt aff002; Linda Reinhard aff001; Sigrid Harendza aff001; Thorsten Wiech aff003; Rolf A. K. Stahl aff001; Elion Hoxha aff001
Působiště autorů:
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff001; Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff002; Division of Nephropathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0221293
Souhrn
Background
Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A2 receptor 1 (PLA2R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA2R1-ab levels correlate with disease activity and treatment response. However, their predictive role for long-term renal outcome is not clear.
Methods
The aim of this prospective observational multicenter study was to investigate the predictive role of PLA2R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA2R1-associated MN. Statistical analyses included Cox proportional hazard models. The primary study endpoint was defined prior to data collection as doubling of serum creatinine or development of end-stage renal disease.
Results
During the median follow-up time of 48 months, 36 (15%) patients reached the study endpoint. Independent predictors for reaching the study endpoint were baseline PLA2R1-ab levels (HR = 1.36, 95%CI 1.11–1.66, p = 0.01), percentage of tubular atrophy and interstitial fibrosis (HR = 1.32, 95%CI 1.03–1.68, p = 0.03), PLA2R1-ab relapse during follow-up (HR = 3.22, 95%CI 1.36–7.60, p = 0.01), and relapse of proteinuria (HR = 2.60, 95%CI 1.17–5.79, p = 0.02). Fifty-four (22%) patients received no immunosuppressive treatment during the study, in 41 (76%) of them PLA2R1-ab spontaneously disappeared during follow-up, 29 (54%) patients had a complete remission of proteinuria, and 19 (35%) had a partial remission. Patients not treated with immunosuppression were more often females and had lower PLA2R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression. However, no conclusion on the efficacy of immunosuppressive therapies can be made, since this was not a randomized controlled study and treatment decisions were not made per-protocol.
Conclusions
PLA2R1-ab levels are, in addition to pre-existing renal damage, predictive factors for long-term outcome and should therefore be considered when deciding the treatment of patients with MN.
Klíčová slova:
Medicine and health sciences – Diagnostic medicine – Signs and symptoms – Proteinuria – Immune suppression – Pathology and laboratory medicine – Pharmacology – Drugs – Immunosuppressives – Cyclophosphamide – Immunology – Pharmaceutics – Drug therapy – Biology and life sciences – Biochemistry – Biomarkers – Creatinine – Developmental biology – Fibrosis – Research and analysis methods – Mathematical and statistical techniques – Statistical methods – Regression analysis – Physical sciences – Mathematics – Statistics
Zdroje
1. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11–21. doi: 10.1056/NEJMoa0810457 19571279
2. Hoxha E, Kneißler U, Stege G, Zahner G, Thiele I, Panzer U, et al. Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy. Kidney Int. 2012;82(7):797–804. doi: 10.1038/ki.2012.209 22673885
3. Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy. Nephrol Dial Transplant. 2013;28(7):1839–1844. doi: 10.1093/ndt/gfs439 23223223
4. Hofstra JM, Debiec H, Short CD, Pellé T, Kleta R, Mathieson PW, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23(10):1735–1743. doi: 10.1681/ASN.2012030242 22956816
5. Timmermans SA, Ayalon R, van Paassen P, Beck LH Jr, van Rie H, Wirtz JJ, et al. Anti-phospholipase A2 receptor antibodies and malignancy in membranous nephropathy. Am J Kidney Dis. 2013;62(6): 1223–1225. doi: 10.1053/j.ajkd.2013.07.019 24021909
6. Hoxha E, Thiele I, Zahner G, Panzer U, Harendza S, Stahl RA. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy. J Am Soc Nephrol. 2014;25(6):1357–1366. doi: 10.1681/ASN.2013040430 24610926
7. Stahl R, Hoxha E, Fechner K. PLA2R autoantibodies and recurrent membranous nephropathy after transplantation. N Engl J Med. 2010;363(5):496–498. doi: 10.1056/NEJMc1003066 20818871
8. Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pellé T, Gaspari F, et al. Anti-phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol. 2015;26(10):2545–2558. doi: 10.1681/ASN.2014070640 25804280
9. Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011;22(8):1543–1550. doi: 10.1681/ASN.2010111125 21784898
10. Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, et al. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017;28(1):348–358. doi: 10.1681/ASN.2016040449 27352623
11. Hoxha E, Harendza S, Pinnschmidt H, Panzer U, Stahl RA. PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system. PLoS One. 2014;9(10):e110681. doi: 10.1371/journal.pone.0110681 25313791
12. Bech AP, Hofstra JM, Brenchley PE, Wetzels JF. Association of anti-PLA2R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(8):1386–1392. doi: 10.2215/CJN.10471013 25035272
13. De Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC. A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2017;28(2):421–430. doi: 10.1681/ASN.2016070776 27777266
14. Kanigicherla D, Gummadova J, McKenzi EA, Roberts SA, Harris S, Nikam M, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int. 2013;83(5):940–948. doi: 10.1038/ki.2012.486 23364522
15. Hoxha E, Harendza S, Pinnschmidt H, Panzer U, Stahl RA. M-type phospholipase A2 receptor autoantibodies and renal function in patients with primary membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(11):1883–1890. doi: 10.2215/CJN.03850414 25267554
16. Thompson A, Cattran DC, Blank M, Nachman PH. Complete and Partial Remission as Surrogate End Points in Membranous Nephropathy. J Am Soc Nephrol. 2015;26(12):2930–2937. doi: 10.1681/ASN.2015010091 26078365
17. Ehrenreich T, Churg J. Pathology of membranous nephropathy. Path Ann. 1968;3 : 145–186.
18. Hoxha E, Beck LH Jr, Wiech T, Tomas NM, Probst C, Mindorf S, et al. An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy. J Am Soc Nephrol. 2017;28(2):520–531. doi: 10.1681/ASN.2016010050 27436855
19. Dähnrich C, Komorowski L, Probst C, Seitz-Polski B, Esnault V, Wetzels JF, et al. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy. Clin Chim Acta. 2013;421 : 213–218. doi: 10.1016/j.cca.2013.03.015 23541686
20. Linting M, Meulman JJ, Groenen PJF, van der Koojj AJ. Nonlinear principal components analysis: introduction and application. Psychol Methods. 2007;12(3):336–358. doi: 10.1037/1082-989X.12.3.336 17784798
21. Linting M, van der Kooij AJ. Nonlinear principal components analysis with CATPCA: a tutorial. J Pers Assess. 2012;94(1):12–25. doi: 10.1080/00223891.2011.627965 22176263
22. Kleinbaum DG, Klein M. Logistic regression. A Self-learning Text. 2nd ed. New York: Springer; 2002. pp. 513.
23. Wei SY, Wang YX, Li JS, Zhao SL, Diao TT, Wang Y, et al. Serum anti-PLA2R antibody predicts treatment outcome in idiopathic membranous nephropathy. Am J Nephrol. 2016;43(2):129–140. doi: 10.1159/000445361 27058841
24. Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, et al. An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant. 2011;26(8):2526–2532. doi: 10.1093/ndt/gfr247 21633097
Článek vyšel v časopise
PLOS One
2019 Číslo 9
- Různé složky stravy mění střevní mikrobiotu. Co to dělá s imunitou?
- Jaké jsou nutriční kompetence (nejen) lékařů napříč světem?
- Prasečí plíce, mRNA vakcíny proti HIV, vypínač jídla a pivaři pod drobnohledem – „jednohubky“ z výzkumu 2025/29
- Nová sonda umí rozsvítit nádory v mozku
- Metamizol v neuropatické bolesti – analgetikum s imunomodulačním potenciálem
Nejčtenější v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania
Zvyšte si kvalifikaci online z pohodlí domova
BONE ACADEMY 2025
nový kurzVšechny kurzy