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Clinical significance of mesangial IgM deposition in patients with IgA nephropathy

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Abstract

Background

Glomerular immunoglobulin G deposition in patients with immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM) deposition in these patients remains to be proven.

Methods

One hundred patients who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were divided into two groups based on mesangial IgM deposition status. Groups were compared for demographic, clinical, and pathologic variables at baseline and in follow-up. Cox regression analysis was performed to evaluate the effect of mesangial IgM positivity on renal survival.

Results

IgM-positive group included 51% of participants. Baseline demographic and clinical parameters were not significantly different between groups. Mesangial IgM deposition was significantly associated with a higher segmental sclerosis score (p = 0.008). At last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the combined primary outcome which includes doubling in serum creatinine or evolution to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p = 0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9–4.5; p < 0.001) and mesangial IgM deposition (HR, 13.2; 95% CI 1.9–93.1; p = 0.01) were found to be independent predictors of unfavorable renal outcomes.

Conclusions

In conclusion, we demonstrated that mesangial IgM deposition independently associated with worse renal outcomes in patients with IgA nephropathy.

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References

  1. Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int. 2004;66(3):920.

    Article  PubMed  Google Scholar 

  2. Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002;347(10):738.

    Article  PubMed  CAS  Google Scholar 

  3. Moriyama T, Tanaka K, Iwasaki C, et al. Prognosis in IgA Nephropathy: 30-year analysis of 1012 Patients at a Single Center in Japan. PLoS One. 2014;9(3):e91756.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;368(25):2402–14.

    Article  PubMed  CAS  Google Scholar 

  5. D’Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histologicalprognostic factors. Am J Kidney Dis 2000;36(2):227–37.

    Article  PubMed  Google Scholar 

  6. Shin DH, Lim BJ, Han IM, et al. Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy. Mod Pathol. 2016;29(7):743.

    Article  PubMed  CAS  Google Scholar 

  7. Strassheim D, Renner B, Panzer S, et al. IgM contributes to glomerular injury in FSGS. J Am Soc Nephrol. 2013;24(3):393–406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Panzer SE, Laskowski J, Renner B, et al. IgM exacerbates glomerular disease progression in complement-induced glomerulopathy. Kidney Int. 2015;88(3):528–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Zhang YM, Gu QH, Huang J, et al. Clinical significance of IgM and C3 glomerular deposition in primary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2016;11(9):1582–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Platt JL, Cascalho M. IgM in the kidney: a multiple personality disorder. Kidney Int. 2015;88(3):439–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Liu Z, Li L. Significance of IgM deposition in IgA nephropathy: an appraisal based on renal re-biopsy. Zhonghua Yi Xue Za Zhi. 1990;70(6):324–6.

    PubMed  CAS  Google Scholar 

  12. Welch TR, McAdams J. Immunoglobulin M and C1q mesangial labeling in IgA nephropathy. Am J Kidney Dis. 1998;32(4):589–92.

    Article  PubMed  CAS  Google Scholar 

  13. Heybeli C, Unlu M, Yildiz S, Çavdar C, Sarioglu S, Camsari T. IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM. Ren Fail. 2015;37(9):1464–9.

    Article  PubMed  CAS  Google Scholar 

  14. Espinosa M, Ortega R, Sánchez M, et al. Spanish Group for Study of Glomerular Diseases (GLOSEN). Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2014;9(5):897–904.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Moriyama T, Shimizu A, Takei T, Uchida K, Honda K, Nitta K. Characteristics of immunoglobulin A nephropathy with mesangial immunoglobulin G and immunoglobulin M deposition. Nephrology (Carlton). 2010;15(8):747–54.

    Article  Google Scholar 

  16. Trimarchi H, Barratt J, Cattran DC, et al. IgAN Classification Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Conference Participants. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91(5):1014. (Epub 2017 Mar 22).

    Article  PubMed  Google Scholar 

  17. Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L. Predicting the risk for dialysis or death in IgA nephropathy. J Am Soc Nephrol. 2011;22(4):752. (Epub 2011 Jan 21).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wakai K, Kawamura T, Endoh M, et al. A scoring system to predict renal outcome in IgA nephropathy: from a nation wide prospective study. Nephrol Dial Transplant. 2006;21(10):2800.

    Article  PubMed  Google Scholar 

  19. Wada Y, Ogata H, Takeshige Y, et al. Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy. Clin Exp Nephrol. 2013;17(1):73–82.

    Article  PubMed  CAS  Google Scholar 

  20. Eison TM, Hastings MC, Moldoveanu Z, et al. Association of IgG co-deposition with serum levels of galactose-deficient IgA1 in pediatric IgA nephropathy. Clin Nephrol. 2012;78(6):465–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhao Y, Zhu L, Liu L, Shi S, Lv J, Zhang H. Pathogenic role of glycan-specific IgG antibodies in IgA nephropathy. BMC Nephrology. 2017;18:301. https://doi.org/10.1186/s12882-017-0722-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol. 2006;17(6):1724.

    Article  PubMed  CAS  Google Scholar 

  23. McMullen ME, Hart ML, Walsh MC, Buras J, Takahashi K, Stahl GL. Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo. Immunobiology. 2006;211(10):759–66.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang M, Takahashi K, Alicot EM, et al. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol. 2006 ;177(7):4727–34.

  25. Busche MN, Pavlov V, Takahashi K, Stahl GL. Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin. Am J Physiol. 2009;297(5):H1853–9.

    CAS  Google Scholar 

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Acknowledgements

We thank to Professor Hülya Ellidokuz for her contribution on statistical analysis.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, School of Medicine, Dokuz Eylul University, Balçova, İzmir, Turkey

    Cihan Heybeli, Mehmet Ası Oktan, Serkan Yıldız, Hayri Üstün Arda, Caner Çavdar, Aykut Sifil, Ali Çelik & Taner Çamsarı

  2. Department of Pathology, School of Medicine, Dokuz Eylul University, İzmir, Turkey

    Mehtat Ünlü & Sülen Sarıoğlu

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  1. Cihan Heybeli
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  2. Mehmet Ası Oktan
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Correspondence to Cihan Heybeli.

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Conflict of interest

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 2018-11-13) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Heybeli, C., Oktan, M.A., Yıldız, S. et al. Clinical significance of mesangial IgM deposition in patients with IgA nephropathy. Clin Exp Nephrol 23, 371–379 (2019). https://doi.org/10.1007/s10157-018-1651-6

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  • DOI: https://doi.org/10.1007/s10157-018-1651-6

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