İdiopatik Membranöz Nefropatide Tedavi Öncesi Serum Kompleman 3 Seviyesi ve Rituksimab Yanıtı

Year 2023, Volume: 18 Issue: 3, 47 - 50, 20.11.2023

Engin Onan Dilek Torun Rüya Özelsancak Hasan Micozkadıoğlu

https://doi.org/10.17517/ksutfd.1366987

Abstract

Amaç: İdiyopatik membranöz nefropati (MN) hastalarında rituksimabın etkinliği rapor edilmiştir. Merkezimizde diğer tedavilere yanıt vermeyen idiyopatik MN hastalarında tanıda kullanılan biyokimyasal testler, immünhistokimyasal profil ve rituksimab yanıtı arasındaki ilişkiyi değerlendirmeyi amaçladık.

Gereç ve Yöntemler: Bu çalışmada 2017-2022 yılları arasında diğer immünsüpresif tedavileri alan ve merkezimizde böbrek biyopsisi yapılan idiyopatik MN'li dokuz hasta değerlendirildi. Tedavi öncesi fosfolipaz A2 antikor düzeyi 6 hastada pozitifti, 3 hastada ise antikor analizi yapılamadı. Tüm hastalara renin-anjiyotensin-aldosteron sistemi (RAAS) blokeri, siklofosfamid, steroid ve kalsinörin inhibitörlerinin ardından ≥2 gram rituksimab verildi.

Bulgular: Çalışmaya dahil edilen dokuz hastanın 7'si (%78,2) erkek olup yaş ortalaması 39,7±13,2 yıl idi. Dört hastada rituksimab tedavisi ile tam remisyon (KR), beş hastada ise kısmi remisyon (PR) görüldü. Renal biyopside sklerotik glomerül sayısı, IgG, A, M, C1q, C3, C4d, fibrinojen, kappa ve lambda boyanması, tübüler atrofi ve interstisyel fibrozis bulguları benzerdi. Ancak serum kompleman 3 (C3) düzeyi normal sınırlar içinde anlamlı derecede düşüktü (1,22 ± 0,26 vs 1,560 ± 0,56 p=0,016). Ortalama arter basıncı kısmi remisyonda olan hastalarda tam remisyonda olanlara göre anlamlı derecede yüksekti (96.22.5 mmHg vs 84.754.27 mmHg, p: 0.018).

Sonuç: İdiyopatik membranöz nefropatili hastalarda tedavi öncesinde normal sınırlar içerisinde düşük bir bazal serum C3 düzeyi, diğer immünsüpresif tedavilere yanıtsızlığın ve rituksimab tedavisine kısmi yanıtın öngörülmesinde yardımcı olabilir.

Keywords

Membranöz Nefropati, Serum Kompleman 3, Rituksimab

Ethical Statement

This study was approved by Baskent University Medical and Health Sciences Research Board.

Supporting Institution

Baskent University

Project Number

1

Pre-Treatment Serum Complement 3 Levels And Rituximab Response In Idiopathic Membranous Nephropathy

Abstract

Objective: The efficacy of rituximab has been reported in patients with idiopathic membranous nephropathy (MN). We aimed to evaluate the relationship between biochemical tests at diagnosis, immunohistochemical profile, and rituximab response in patients with idiopathic MN unresponsive to other therapies in our center.

Material and Methods: In this study, nine patients with idiopathic MN who received other immunosuppressive therapies between 2017-2022 and who underwent renal biopsy in our center were evaluated. Pre-treatment phospholipase A2 antibody levels were positive in 6 patients, and antibodies could not be analyzed in 3 patients. All patients received rituximab ≥2 grams after renin-angiotensin-aldosterone system (RAAS) blocker, cyclophosphamide, steroid, and calcineurin inhibitors.

Results: Of the nine patients included in the study, 7 (78.2%) were male, and the mean age was 39.713.2 years. Four patients had complete remission (CR) with rituximab treatment, and five had partial remission (PR). Sclerotic glomeruli count, IgG, A, M, C1q, C3, C4d, fibrinogen, kappa and lambda staining, tubular atrophy, and interstitial fibrosis findings on renal biopsy were similar. However, the serum complement 3 (C3) level was significantly lower within normal limits (1.22  0.26 vs 1.560  0.56 p=0.016). The mean arterial pressure was significantly higher (96.22.5 mmHg vs 84.754.27 mmHg, p=0.018) in patients with partial remission compared to those with complete remission.

Conclusion: A low baseline serum C3 level within normal limits before treatment in patients with idiopathic membranous nephropathy may help predicting unresponsiveness to other immunosuppressive therapies and partial response to rituximab treatment.

Keywords

Serum Complement 3, Rituximab, membranous nephropathy

Ethical Statement

This study was approved by Baskent University Medical and Health Sciences Research Board.

Supporting Institution

Baskent University

Project Number

1

References

• Salant DJ, Quigg RJ, Cybulsky AV. Heymann nephritis: mechanisms of renal injury. Kidney Int. 1989;35(4):976-84.
• Doi T, Mayumi M, Kanatsu K, Suehiro F, Hamashima Y. Distribution of IgG subclasses in membranous nephropathy. Clin Exp Immunol. 1984;58:57-62.
• Segawa Y, Hisano S, Matsushita M, Fujita T, Hirose S, Takeshita M, et al. IgG subclasses and complement pathway in segmental and global membranous nephropathy. Pediatr Nephrol. 2010;25(6):1091-9.
• Zhang R, Zheng ZY, Lin JS, Qu LJ, Zheng F. The continual presence of C3d but not IgG glomerular capillary deposition in stage I idiopathic membranous nephropathy in patients receiving corticosteroid treatment. Diagn Pathol. 2012;7:109.
• Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276.
• Ligtenberg G, Arends S, Stegeman CA, De Leeuw K. Predictors of Renal Flares and Long-Term Renal Outcome in Patients with Lupus Nephritis: Results from Daily Clinical Practice. Clin. Exp. Rheumatol. 2022;40:33–38.
• Rossi GM, Maggiore U, Peyronel F, Fenaroli P, Delsante M, Benigno GD, et al. Persistent Isolated C3 Hypocomplementemia as a Strong Predictor of End-Stage Kidney Disease in Lupus Nephritis. Kidney Int. Rep. 2022;7:2647–2656.
• Liu J, Zha Y, Zhang P, He P, He L. The Association Between Serum Complement 4 and Kidney Disease Progression in Idiopathic Membranous Nephropathy: A Multicenter Retrospective Cohort Study. Front Immunol. 2022;13:896654.
• Zhang Y, Duan SW, Chen P, Yin Z, Wang Y, Cai GY, et al. Relationship between serum C3/C4 ratio and prognosis of immunoglobulin A nephropathy based on propensity score matching. Chin Med J (Engl). 2020;133(6):631-637.
• Di Gaetano N, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E, et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol. 2003;171(3):1581-7.
• Cragg MS, Morgan SM, Chan HT, Morgan BP, Filatov AV, et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood. 2003;101(3):1045-1052.
• Anderson DR, Grillo-López A, Varns C, Chambers KS, Hanna N. Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma. Biochem Soc Trans. 1997;25(2):705-708.
• Van der Kolk LE, Grillo-López AJ, Baars JW, Hack CE, van Oers MH. Complement activation plays a key role in the side-effects of rituximab treatment. Br J Haematol. 2001;115(4):807-811.