Clinicopathological and long-term prognostic features of membranous nephropathy with crescents: a Japanese single-center experience

Abstract

Background

Three recent studies from the United States and China reported the clinicopathological features and short-term prognosis in patients with membranous nephropathy (MN) and crescents in the absence of secondary MN, anti-glomerular basement membrane (GBM) antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA).

Methods

We compared clinicopathological and prognostic features in 16 MN patients with crescents (crescent group) and 38 MN patients without crescents (control group), in the absence of secondary MN, anti-GBM antibodies, and ANCA. Median follow-up periods in the crescent and control groups were 79 and 50 months, respectively.

Results

Decreased estimated glomerular filtration rates (<50 mL/min/1.73 m2), glomerulosclerosis, and moderate-to-severe interstitial fibrosis were more frequently observed in the crescent group than in the control group (P = 0.043, P = 0.004, and P = 0.035, respectively). Positive staining rates for glomerular IgG2 and IgG4 were significantly different between the 2 groups (P = 0.032, P = 0.006, respectively). Doubling of serum creatinine during follow-up was more frequently observed in the crescent group than in the control group (P = 0.002), although approximately two-thirds of patients in the crescent group were treated with immunosuppressive therapy. Crescent formation and interstitial fibrosis were risks for doubling of serum creatinine [hazard ratio (HR) = 10.506, P = 0.012; HR = 1.140, P = 0.009, respectively].

Conclusions

This is the first Japanese study demonstrating significant differences in clinicopathological and prognostic features between the 2 groups. Most patients in the crescent group may develop a long-term decline in renal function despite immunosuppressive therapy.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    Francis JM, Beck LH Jr, Salant DJ. Membranous nephropathy: a journey from bench to bedside. Am J Kidney Dis. 2016;68:138–47.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    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;361:11–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Akiyama S, Akiyama M, Imai E, Ozaki T, Matsuo S, Maruyama S. Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol. 2015;19:653–60.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Iwakura T, Ohashi N, Kato A, Baba S, Yasuda H. Prevalence of enhanced granular expression of thrombospondin type-1 domain-containing 7A in the glomeruli of Japanese patients with idiopathic membranous nephropathy. PLoS ONE. 2015;10:e0138841.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125:S41–52.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Imai H, Hamai K, Komatsuda A, Ohtani H, Miura AB. IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis. Kidney Int. 1997;51:270–6.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Omokawa A, Komatsuda A, Nara M, Fujiwara S, Sato R, Togashi M, et al. Distribution of IgG subclass deposits in patients with membranous nephropathy and anti-U1 ribonucleoprotein antibody. Nephrol Dial Transplant. 2012;27:1937–41.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Nagahama K, Matsushita H, Hara M, Ubara Y, Hara S, Yamada A. Bucillamine induces membranous glomerulonephritis. Am J Kidney Dis. 2002;39:706–12.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Ohtani H, Wakui H, Komatsuda A, Okuyama S, Masai R, Maki N, et al. Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrol Dial Transplant. 2004;19:574–9.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Moroni G, Ponticelli C. Rapidly progressive crescentic glomerulonephritis: early treatment is a must. Autoimmun Rev. 2014;13:723–9.

    Article  PubMed  Google Scholar 

  11. 11.

    Basford AW, Lewis J, Dwyer JP, Fogo AB. Membranous nephropathy with crescents. J Am Soc Nephrol. 2011;22:1804–8.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Nasr SH, Said SM, Valeri AM, Stokes MB, Masani NN, D’Agati VD, et al. Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis. Clin J Am Soc Nephrol. 2009;4:299–308.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Barrett CM, Troxell ML, Larsen CP, Houghton DC. Membranous glomerulonephritis with crescents. Int Urol Nephrol. 2014;46:963–71.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Kwan JT, Moore RH, Dodd SM, Cunningham J. Crescentic transformation in primary membranous glomerulonephritis. Postgrad Med J. 1991;67:574–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Tse WY, Howie AJ, Adu D, Savage CO, Richards NT, Wheeler DC, et al. Association of vasculitic glomerulonephritis with membranous nephropathy: a report of 10 cases. Nephrol Dial Transplant. 1997;12:1017–27.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Arrizabalaga P, Boix AS, Rabassa AT, Tey AD, Torrellas LR. Monoclonal antibody analysis of crescentic membranous glomerulonephropathy. Am J Nephrol. 1998;18:77–82.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Unver S, Haholu A, Atasoyu EM, Karatas M, Akcan R, Evrenkaya TR. A rare complication of idiopathic membranous nephropathy: crescent transformation. Ren Fail. 2008;30:573–5.

    Article  PubMed  Google Scholar 

  18. 18.

    Gadonski G, Poli-de-Figueiredo CE, Fervenza FC, Singh AK, Tettamanzy FM, Antonello IC, et al. Rapidly deteriorating kidney function in a young man previously diagnosed with membranous nephropathy. Nephron Clin Pract. 2010;115:c100–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Rodriguez EF, Nasr SH, Larsen CP, Sethi S, Fidler ME, Cornell LD. Membranous nephropathy with crescents: a series of 19 cases. Am J Kidney Dis. 2014;64:66–73.

    Article  PubMed  Google Scholar 

  20. 20.

    Wang J, Zhu P, Cui Z, Qu Z, Zhang Y, Wang F, et al. Clinical features and outcomes in patients with membranous nephropathy and crescent formation. Medicine. 2015;94:e2294.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Qian Y, Zuo K, Shijun L, Li X, Zeng C, Liu Z, et al. Clinicopathological analysis of membranous nephropathy with crescents. Int J Clin Pathol. 2016;9:1947–53.

    Google Scholar 

  22. 22.

    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    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;26:2526–32.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Ozawa M, Komatsuda A, Ohtani H, Nara M, Sato R, Togashi M, et al. Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience. Clin Exp Nephrol. 2017;21:212–27.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Komatsuda A, Masai R, Ohtani H, Maki N, Sawada K, Wakui H. Monoclonal immunoglobulin deposition disease associated with membranous features. Nephrol Dial Transplant. 2008;23:3888–94.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl. 2012;2:186–97.

    Article  Google Scholar 

  27. 27.

    Schwartz MM. Membranous glomerulonephritis. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, editors. Heptinstall’s pathology of the kidney. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 205–51.

    Google Scholar 

Download references

Acknowledgements

The authors thank all the doctors in our affiliated hospitals for the referral of patients.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Atsushi Komatsuda.

Ethics declarations

Disclosure

All the authors have declared no competing interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 1026) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saito, M., Komatsuda, A., Sato, R. et al. Clinicopathological and long-term prognostic features of membranous nephropathy with crescents: a Japanese single-center experience. Clin Exp Nephrol 22, 365–376 (2018). https://doi.org/10.1007/s10157-017-1465-y

Download citation

Keywords

  • Clinicopathological study
  • Crescent formation
  • IgG-subclass
  • Membranous nephropathy
  • Prognosis