THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION  IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY

Oto Özgür; Dirim Ahmet; Şafak Seda; Güller Nurana; Demir Erol; Artan Ayşe Serra; Özlük Mesude; Uçar Ali; Soltanova Lala; Nuriyev Kanan; Yazıcı Halil; Kerem Çalışkan Yaşar

doi:https://dx.doi.org/10.26650/IUITFD.1126241

Research Article

DOI :10.26650/IUITFD.1126241 IUP :10.26650/IUITFD.1126241 Full Text (PDF)

THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY

Özgür Akın Oto, Şafak Mirioğlu, Ahmet Burak Dirim, Seda Şafak, Nurana Güller, Erol Demir, Ayşe Serra Artan, Mesude Yasemin Özlük, Ali Rıza Uçar, Lala Soltanova, Kanan Nuriyev, Halil Yazıcı, Yaşar Kerem Çalışkan

Objective: The purpose of this study was to investigate the impact of glomerular C3 accumulation density on clinical, histopathological parameters and outcomes in elderly (>60 years) individuals with primary membranous nephropathy (PMN). Material and Methods: In this study, we examined the patients (n=105) in two groups according to the C3 staining density in kidney biopsy samples as low intensity (C3: 1+; LI group) and high intensity (C3: 2+ or C3: 3+; HI group). The primary endpoint of our study was the end-stage renal disease, and the secondary endpoints were the development of partial remission (PR) or complete remission (CR). Results: At the end of the follow-up (mean 30.6 months), more patients achieved the primary endpoint, and fewer patients achieved the secondary endpoints in the HI group compared to the LI group. (p=0.015 and p=0.016, respectively). Moreover, the glomerular filtration rate (eGFR) was lower (p<0.001), and proteinuria was higher in the HI group (p=0.018). Kaplan-Meier survival analysis revealed that renal survival (p=0.031) was lower in the HI group compared to the LI group. In the multivariate logistic regression analyses, no predictive parameters could be detected for the endpoints. Conclusion: Intense glomerular C3 deposition in elderly (>60 years) patients with PMN may be related to poor clinical outcomes.

Keywords: Complementary system, C3, older age, membranous nephropathy

DOI :10.26650/IUITFD.1126241 IUP :10.26650/IUITFD.1126241 Full Text (PDF)

İLERİ YAŞLI PRİMER MEMBRANÖZ NEFROPATİLİ HASTALARDA GLOMERÜLER C3 BİRİKİMİNİN ÖNEMİ

Amaç: Bu çalışmada, primer membranöz nefropatili (PMN) yaşlı (>60 yaş) hastalarda glomerüler C3 birikim yoğunluğunun klinik, histopatolojik özellikler ve hastalığın seyri üzerindeki etkilerini araştırmayı amaçladık. Gereç ve Yöntem: Bu retrospektif gözlemsel çalışmaya dahil ettiğimiz PMN’li 105 hastayı böbrek biyopsi örneklerinde C3 birikiminin yoğunluğuna göre düşük yoğunluklu (C3 1+; LI) ve yüksek yoğunluklu (C3 2+ veya C3 3+; HI) olmak üzere iki grupta inceledik. Birincil sonlanım noktası son evre böbrek hastalığı, ikincil sonlanım noktaları ise tam (CR) veya kısmi remisyon (PR) idi. Bulgular: İzlem sonunda (ortanca 30,6 ay), HI grubunda LI grubuna kıyasla daha fazla hasta birincil noktaya ulaşırken daha az hasta ikincil son noktalara erişti (sırasıyla p=0,015 ve p=0,016). Ayrıca HI grubunda LI grubuna göre glomerüler filtrasyon hızı (eGFR) daha düşük (p<0,001), proteinüri ise daha fazlaydı (p=0,018). Kaplan-Meier analizlerinde böbrek sağ kalımının (p=0,031) HI grubunda LI grubundan daha düşük olduğu saptandı. Çok değişkenli lojistik regresyon analizlerinde, son noktalar öngördürücü bir parametre saptanamadı. Sonuç: Yoğun glomerüler C3 birikimi, PMN’li yaşlı hastalarda olumsuz klinik sonuçlarla ilişkilidir.

Keywords: Kompleman sistemi, C3, ileri yaş, membranöz nefropati

References

1. Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: A 50-year odyssey. Am J Kidney Dis 2010;56(1):157-67. [CrossRef] google scholar
2. Zeng CH, Chen HM, Wang RS, Chen Y, Zhang SH, Liu L, et al. Etiology and clinical characteristics of membranous nephropathy in Chinese patients. Am J Kidney Dis 2008;52(4):691-8. [CrossRef] google scholar
3. Feng Z, Wang S, Huang Y, Liang X, Shi W, Zhang B. A follow-up analysis of positron emission tomography/computed tomography in detecting hidden malignancies at the time of diagnosis of membranous nephropathy. Oncotarget 2016;7(9):9645. [CrossRef] google scholar
4. Seitz-Polski B, Dolla G, Payre C, Girard CA, Polidori J, Zorzi K, et al. Epitope spreading of autoantibody response to PLA2R associates with poor prognosis in membranous nephropathy. J Am Soc Nephrol 2016;27(5):1517-33. [CrossRef] google scholar
5. Beck Jr LH, 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. [CrossRef] google scholar
6. Tomas NM, Beck Jr LH, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 2014;371(24):2277-87. [CrossRef] google scholar
7. Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, et al. Exostosin 1/exostosin 2-associated membranous nephropathy. J Am Soc Nephrol 2019;30(6):1123-36. [CrossRef] google scholar
8. Pei Y, Cattran D, Greenwood C. Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. Kidney Int 1992;42(4):960-6. [CrossRef] google scholar
9. Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, et al. prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993;329(2):85-9. [CrossRef] google scholar
10. Kanigicherla D, Gummadova J, McKenzie 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):940-8. [CrossRef] google scholar
11. Davison A, Cameron J, Kerr D, Ogg C, Wilkinson R. The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults. Clin Nephrol 1984;22(2):61-7. google scholar
12. Ma H, Sandor DG, Beck Jr LH. The role of complement in membranous nephropathy. Semin Nephrol 2013;33(6):531-42. [CrossRef] google scholar
13. Sethi S, Nasr SH, De Vriese AS, Fervenza FC. C4d as a diagnostic tool in proliferative GN. J Am Soc Nephrol 2015;26(11):2852-9. [CrossRef] google scholar
14. Ma H, Sandor DG, Beck LH, Jr. The role of complement in membranous nephropathy. Semin Nephrol 2013;33(6):531-42. [CrossRef] google scholar
15. Oto OA, Demir E, Mirioglu S, Dirim AB, Ozluk Y, Cebeci E, et al. Clinical significance of glomerular C3 deposition in primary membranous nephropathy. J Nephrol 2021;34(2):581-7. [CrossRef] google scholar
16. Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol 2016;12(7):383-401. [CrossRef] google scholar
17. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, et al. Augmented Wnt signaling in a mammalian model of accelerated aging. Science 2007;317(5839):803-06. [CrossRef] google scholar
18. Liu D, Lun L, Huang Q, Ning Y, Zhang Y, Wang L, et al. Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice. Kidney Int 2018;94(2):268-79. [CrossRef] google scholar
19. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, et al. Cyclosporine in patients with steroid-resistant membranous nephropathy: A randomized trial. Kidney Int 2001;59(4):1484-90. [CrossRef] google scholar
20. Cattran DC, Feehally J, Cook HT, Liu ZH, Fervenza F, Mezzano S, et al. Kidney disease: Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Supplements 2012;2:139-274. google scholar
21. Ehrenreich T, Porush JG, Churg J, Garfinkel L, Glabman S, Goldstein MH, et al. Treatment of idiopathic membranous nephropathy. N Engl J Med 1976;295(14):741-6. [CrossRef] google scholar
22. Franzin R, Stasi A, Fiorentino M, Stallone G, Cantaluppi V, Gesualdo L, et al. Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage. Front Immunol 2020;11:734. [CrossRef] google scholar
23. McGeer EG, Klegeris A, McGeer PL. Inflammation, the complement system and the diseases of aging. Neurobiol Aging 2005;26(1):94-7. [CrossRef] google scholar
24. Cribbs DH, Berchtold NC, Perreau V, Coleman PD, Rogers J, Tenner AJ, et al. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. J Neuroinflammation 2012;9(1):1-18. [CrossRef] google scholar
25. Stephan AH, Madison DV, Mateos JM, Fraser DA, Lovelett EA, Coutellier L, et al. A dramatic increase of C1q protein in the CNS during normal aging. J Neurosci 2013;33(33):13460-74. [CrossRef] google scholar
26. Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol 2016;12(7):383-401. [CrossRef] google scholar
27. Castellano G, Trouw LA, Fiore N, Daha MR, Schena FP, van Kooten C. Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis. Mol Immunol 2010;47(11-12):2129-37. [CrossRef] google scholar
28. Fearn A, Sheerin NS. Complement activation in progressive renal disease. World J Nephrol 2015;4(1):31-40. [CrossRef] google scholar
29. Thurman JM. Complement in kidney disease: core curriculum 2015. Am J Kidney Dis 2015;65(1):156-68. [CrossRef] google scholar
30. Erwin D. The clinical course of idiopathic membranous nephropathy. Mayo Clin Proc 1973;48:697-712. google scholar
31. Beregi E, Varga I. Analysis of 260 cases of membranous glomerulonephritis in renal biopsy material. Clin Nephrol 1974;2(6):215-21. google scholar
32. Abe S, Amagasaki Y, Konishi K, Kato E, Iyori S, Sakaguchi H. Idiopathic membranous glomerulonephritis: aspects of geographical differences. J Clin Pathol 1986;39(11):1193-8. [CrossRef] google scholar
33. Brenchley PE, Coupes B, Short CD, O’Donoghue DJ, Ballardie FW, Mallick NP. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy. Kidney Int 1992;41(4):933-7. [CrossRef] google scholar
34. 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. Ped Nephrol 2010;25(6):1091-9. [CrossRef] google scholar
35. Borza DB. Alternative pathway dysregulation and the conundrum of complement activation by IgG4 immune complexes in membranous nephropathy. Front Immunol 2016;7:157. [CrossRef] google scholar
36. Marx BE, Marx M. Prediction in idiopathic membranous nephropathy. Kidney Int 1999;56(2):666-73. [CrossRef] google scholar
37. Troyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int 2006;69(9):1641-8. [CrossRef] google scholar
38. Zhang XD, Cui Z, Zhang MF, Wang J, Zhang YM, Qu Z, et al. Clinical implications of pathological features of primary membranous nephropathy. BMC Nephrol 2018;19(1):1-9. [CrossRef] google scholar
39. Yoshimoto K, Yokoyama H, Wada T, Furuichi K, Sakai N, Iwata Y, et al. Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy. Kidney Int 2004;65(1):148-53. [CrossRef] google scholar
40. Cattran D. Management of membranous nephropathy: when and what for treatment. J Am Soc Nephrol 2005;16(5):1188-94. [CrossRef] google scholar
41. Sprangers B, Bomback AS, Cohen SD, Radhakrishnan J, Valeri A, Markowitz GS, et al. Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol 2012;36(1):78-89. [CrossRef] google scholar

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APA

Oto, Ö.A., Mirioğlu, Ş., Dirim, A.B., Şafak, S., Güller, N., Demir, E., Artan, A., Özlük, M.Y., Uçar, A.R., Soltanova, L., Nuriyev, K., Yazıcı, H., & Kerem Çalışkan, Y. (2022). THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY. Journal of Istanbul Faculty of Medicine, 85(4), 541-547. https://doi.org/10.26650/IUITFD.1126241

AMA

Oto Ö A, Mirioğlu Ş, Dirim A B, Şafak S, Güller N, Demir E, Artan A, Özlük M Y, Uçar A R, Soltanova L, Nuriyev K, Yazıcı H, Kerem Çalışkan Y. THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY. Journal of Istanbul Faculty of Medicine. 2022;85(4):541-547. https://doi.org/10.26650/IUITFD.1126241

ABNT

Oto, Ö.A.; Mirioğlu, Ş.; Dirim, A.B.; Şafak, S.; Güller, N.; Demir, E.; Artan, A.; Özlük, M.Y.; Uçar, A.R.; Soltanova, L.; Nuriyev, K.; Yazıcı, H.; Kerem Çalışkan, Y. THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 85, n. 4, p. 541-547, 2022.

Chicago: Author-Date Style

Oto, Özgür Akın, and Şafak Mirioğlu and Ahmet Burak Dirim and Seda Şafak and Nurana Güller and Erol Demir and Ayşe Serra Artan and Mesude Yasemin Özlük and Ali Rıza Uçar and Lala Soltanova and Kanan Nuriyev and Halil Yazıcı and Yaşar Kerem Çalışkan. 2022. “THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY.” Journal of Istanbul Faculty of Medicine 85, no. 4: 541-547. https://doi.org/10.26650/IUITFD.1126241

Chicago: Humanities Style

Oto, Özgür Akın, and Şafak Mirioğlu and Ahmet Burak Dirim and Seda Şafak and Nurana Güller and Erol Demir and Ayşe Serra Artan and Mesude Yasemin Özlük and Ali Rıza Uçar and Lala Soltanova and Kanan Nuriyev and Halil Yazıcı and Yaşar Kerem Çalışkan. “THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY.” Journal of Istanbul Faculty of Medicine 85, no. 4 (Nov. 2024): 541-547. https://doi.org/10.26650/IUITFD.1126241

Harvard: Australian Style

Oto, ÖA & Mirioğlu, Ş & Dirim, AB & Şafak, S & Güller, N & Demir, E & Artan, A & Özlük, MY & Uçar, AR & Soltanova, L & Nuriyev, K & Yazıcı, H & Kerem Çalışkan, Y 2022, 'THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY', Journal of Istanbul Faculty of Medicine, vol. 85, no. 4, pp. 541-547, viewed 18 Nov. 2024, https://doi.org/10.26650/IUITFD.1126241

Harvard: Author-Date Style

Oto, Ö.A. and Mirioğlu, Ş. and Dirim, A.B. and Şafak, S. and Güller, N. and Demir, E. and Artan, A. and Özlük, M.Y. and Uçar, A.R. and Soltanova, L. and Nuriyev, K. and Yazıcı, H. and Kerem Çalışkan, Y. (2022) ‘THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY’, Journal of Istanbul Faculty of Medicine, 85(4), pp. 541-547. https://doi.org/10.26650/IUITFD.1126241 (18 Nov. 2024).

MLA

Oto, Özgür Akın, and Şafak Mirioğlu and Ahmet Burak Dirim and Seda Şafak and Nurana Güller and Erol Demir and Ayşe Serra Artan and Mesude Yasemin Özlük and Ali Rıza Uçar and Lala Soltanova and Kanan Nuriyev and Halil Yazıcı and Yaşar Kerem Çalışkan. “THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY.” Journal of Istanbul Faculty of Medicine, vol. 85, no. 4, 2022, pp. 541-547. [Database Container], https://doi.org/10.26650/IUITFD.1126241

Vancouver

Oto ÖA, Mirioğlu Ş, Dirim AB, Şafak S, Güller N, Demir E, Artan A, Özlük MY, Uçar AR, Soltanova L, Nuriyev K, Yazıcı H, Kerem Çalışkan Y. THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY. Journal of Istanbul Faculty of Medicine [Internet]. 18 Nov. 2024 [cited 18 Nov. 2024];85(4):541-547. Available from: https://doi.org/10.26650/IUITFD.1126241 doi: 10.26650/IUITFD.1126241

ISNAD

Oto, ÖzgürAkın - Mirioğlu, Şafak - Dirim, AhmetBurak - Şafak, Seda - Güller, Nurana - Demir, Erol - Artan, Ayşe Serra - Özlük, MesudeYasemin - Uçar, AliRıza - Soltanova, Lala - Nuriyev, Kanan - Yazıcı, Halil - Kerem Çalışkan, Yaşar. “THE IMPORTANCE OF GLOMERULAR C3 ACCUMULATION IN ELDERLY PATIENTS WITH PRIMARY MEMBRANOUS NEPHROPATHY”. Journal of Istanbul Faculty of Medicine 85/4 (Nov. 2024): 541-547. https://doi.org/10.26650/IUITFD.1126241

Volume 85, Issue 42022, P. 541-547

TIMELINE

Submitted	05.06.2022
Accepted	05.07.2022
Published Online	17.08.2022

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Journal of Istanbul Faculty of Medicine