Skip to main content
SpringerLink
Log in

Clinicopathological significance of glomerular capillary IgA deposition in childhood IgA nephropathy

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

IgA nephropathy (IgAN) is characterized by predominant mesangial IgA deposition. Some patients with IgAN demonstrate IgA deposition in glomerular peripheral capillaries (cap-IgA). The clinicopathological significance of cap-IgA remains incompletely investigated in children.

Methods

We retrospectively analyzed 503 consecutive cases of biopsy-proven childhood IgAN between July 1976 and June 2013 to compare clinical and pathological features between IgAN patients with and without cap-IgA.

Results

Among the 503 patients, 30 (6.0%) had cap-IgA. We found significant differences in proteinuria (2.0 vs. 0.5 g/day/m2, p < 0.0001), time from onset to kidney biopsy (2.2 vs. 8.3 months, p < 0.0001), and rate of proteinuria remission after treatment (23.3% vs. 48.0%, p = 0.007) between both groups. Pathological analysis revealed significant differences in M1 (83.3% vs. 56.0%, p = 0.002), ratio of subendothelial electron dense deposits (EDDs, 58.6% vs. 16.5%, p < 0.0001) and subepithelial EDDs (48.3% vs. 16.5%, p = 0.0001), and glomerular basement membrane (GBM) lysis (58.6% vs. 27.1%, p = 0.0006) between both groups. More than half of cap-IgA patients (17/30, 56.7%), whereas only 26.2% of non-cap-IgA patients (124/473), were treated with immunosuppressive treatments. Six of 30 cases (20%) with cap-IgA reached glomerular filtration rate (GFR) categories G3a–G5 (estimated GFR < 60 ml/min/1.73 m2) at most recent observation (mean observation period: 7.0 ± 4.0 years). According to Kaplan-Meier analysis, patients with cap-IgA had significantly lower kidney survival curves than non-cap-IgA patients (72.8% vs. 97.2% at 10 years, p < 0.0001).

Conclusions

Cap-IgA is associated with acute inflammation with GBM changes, resulting in refractory heavier proteinuria. Cap-IgA may represent a poor prognostic factor.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Donadio JV, Grande JP (2002) IgA nephropathy. N Engl J Med 347:738–748. https://doi.org/10.1056/NEJMra020109

    Article  CAS  PubMed  Google Scholar 

  2. Alexopoulos E (2004) Treatment of primary IgA nephropathy. Kidney Int 65:341–355. https://doi.org/10.1111/j.1523-1755.2004.00437.x

    Article  PubMed  Google Scholar 

  3. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator S, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Leung CB, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 76:534–545. https://doi.org/10.1038/ki.2009.243

    Article  Google Scholar 

  4. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 76:546–556. https://doi.org/10.1038/ki.2009.168

    Article  Google Scholar 

  5. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator SN, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo AB, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2010) The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 77:921–927. https://doi.org/10.1038/ki.2010.43

    Article  CAS  Google Scholar 

  6. Haas M, Verhave JC, Liu ZH, Alpers CE, Barratt J, Becker JU, Cattran D, Cook HT, Coppo R, Feehally J, Pani A, Perkowska-Ptasinska A, Roberts IS, Soares MF, Trimarchi H, Wang S, Yuzawa Y, Zhang H, Troyanov S, Katafuchi R (2017) A multicenter study of the predictive value of crescents in IgA Nephropathy. J Am Soc Nephrol 28:691–701. https://doi.org/10.1681/ASN.2016040433

    Article  CAS  PubMed  Google Scholar 

  7. Yoshimura M, Kida H, Abe T, Takeda S, Katagiri M, Hattori N (1987) Significance of IgA deposits on the glomerular capillary walls in IgA nephropathy. Am J Kidney Dis 9:404–409. https://doi.org/10.1016/s0272-6386(87)80143-9

    Article  CAS  PubMed  Google Scholar 

  8. Bellur SS, Troyanov S, Cook HT, Roberts IS, Working Group of International IgA Nephropathy Network and Renal Pathology Society (2011) Immunostaining findings in IgA nephropathy: correlation with histology and clinical outcome in the Oxford classification patient cohort. Nephrol Dial Transplant 26:2533–2536. https://doi.org/10.1093/ndt/gfq812

    Article  PubMed  Google Scholar 

  9. Alvarado AS, Andeen NK, Brodsky S, Hinton A, Nadasdy T, Alpers CE, Blosser C, Najafian B, Rovin BH (2018) Location of glomerular immune deposits, not codeposition of immunoglobulin G, influences definitive renal outcomes in immunoglobulin A nephropathy. Nephrol Dial Transplant 33:1168–1175. https://doi.org/10.1093/ndt/gfx238

    Article  CAS  PubMed  Google Scholar 

  10. Hattori S, Karashima S, Furuse A, Terashima T, Hiramatsu M, Murakami M, Matsuda I (1985) Clinicopathological correlation of IgA nephropathy in children. Am J Nephrol 5:182–189. https://doi.org/10.1159/000166930

    Article  CAS  PubMed  Google Scholar 

  11. Andreoli SP, Yum MN, Bergstein JM (1986) IgA nephropathy in children: significance of glomerular basement membrane deposition of IgA. Am J Nephrol 6:28–33. https://doi.org/10.1159/000167049

    Article  CAS  PubMed  Google Scholar 

  12. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    CAS  PubMed  Google Scholar 

  13. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637. https://doi.org/10.1681/ASN.2008030287

    Article  PubMed  PubMed Central  Google Scholar 

  14. (2013) Chapter 1: Definition and classification of CKD. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:19–62. https://doi.org/10.1038/kisup.2012.64

  15. Yoshikawa N, Ito H, Nakamura H (1992) Prognostic indicators in childhood IgA nephropathy. Nephron 60:60–67. https://doi.org/10.1159/000186706

    Article  CAS  PubMed  Google Scholar 

  16. Shin DH, Lim BJ, Han IM, Han SG, Kwon YE, Park KS, Lee MJ, Oh HJ, Park JT, Han SH, Kang SW, Yoo TH (2016) Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy. Mod Pathol 29:743–752. https://doi.org/10.1038/modpathol.2016.77

    Article  CAS  PubMed  Google Scholar 

  17. Katafuchi R, Nagae H, Masutani K, Tsuruya K, Mitsuiki K (2019) Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy. Clin Exp Nephrol 23:169–181. https://doi.org/10.1007/s10157-018-1619-6

    Article  CAS  PubMed  Google Scholar 

  18. Heybeli C, Oktan MA, Yıldız S, Arda HÜ, Ünlü M, Çavdar C, Sifil A, Çelik A, Sarıoğlu S, Çamsarı T (2019) Clinical significance of mesangial IgM deposition in patients with IgA nephropathy. Clin Exp Nephrol 23:371–379. https://doi.org/10.1007/s10157-018-1651-6

    Article  CAS  PubMed  Google Scholar 

  19. Andreoli SP, Bergstein JM (1989) Treatment of severe IgA nephropathy in children. Pediatr Nephrol 3:248–253. https://doi.org/10.1007/BF00858524

    Article  CAS  PubMed  Google Scholar 

  20. Murakami M, Yamamoto H, Ueda Y, Murakami K, Yamauchi K (1991) Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol 5:50–53. https://doi.org/10.1007/BF00852844

    Article  CAS  PubMed  Google Scholar 

  21. Murakami M, Hayakawa M, Yanagihara T, Hukunaga Y (2005) Proteinuria screening for children. Kidney Int Suppl 94:S23–S27. https://doi.org/10.1111/j.1523-1755.2005.09406.x

    Article  Google Scholar 

  22. Nam KH, Joo YS, Lee C, Lee S, Kim J, Yun HR, Park JT, Chang TI, Ryu DR, Yoo TH, Chin HJ, Kang SW, Jeong HJ, Lim BJ, Han SH, Korean GlomeruloNEphritis sTudy (KoGNET) Group (2020) Predictive value of mesangial C3 and C4d deposition in IgA nephropathy. Clin Immunol 211:108331. https://doi.org/10.1016/j.clim.2019.108331

    Article  CAS  PubMed  Google Scholar 

  23. Yoshikawa N, Ito H, Nakahara C, Yoshiara S, Yoshiya K, Matsuo T, Hasegawa O, Hazikano H, Okada S (1985) Glomerular electron-dense deposits in childhood IgA nephropathy. Virchows Arch A Pathol Anat Histopathol 406:33–43. https://doi.org/10.1007/BF00710555

    Article  CAS  PubMed  Google Scholar 

  24. Yoshiara S, Yoshikawa N, Matsuo T (1987) Immunoelectron microscopic study of childhood IgA nephropathy and Henoch-Schönlein nephritis. Virchows Arch A Pathol Anat Histopathol 412:95–102. https://doi.org/10.1007/BF00716180

    Article  CAS  PubMed  Google Scholar 

  25. Lee HS, Choi Y, Lee JS, Yu BH, Koh HI (1989) Ultrastructural changes in IgA nephropathy in relation to histologic and clinical data. Kidney Int 35:880–886. https://doi.org/10.1038/ki.1989.68

    Article  CAS  PubMed  Google Scholar 

  26. Kitamura M, Obata Y, Ota Y, Muta K, Yamashita H, Harada T, Mukae H, Nishino T (2019) Significance of subepithelial deposits in patients diagnosed with IgA nephropathy. PLoS One 14:e0211812. https://doi.org/10.1371/journal.pone.0211812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hara M, Endo Y, Nihei H, Hara S, Fukushima O, Mimura N (1980) IgA nephropathy with subendothelial deposits. Virchows Arch A Pathol Anat Histol 386:249–263. https://doi.org/10.1007/BF00427296

    Article  CAS  PubMed  Google Scholar 

  28. Yoshikawa N, Yoshiara S, Yoshiya K, Matsuo T, Okada S (1986) Lysis of the glomerular basement membrane in children with IgA nephropathy and Henoch-Schönlein nephritis. J Pathol 150:119–126. https://doi.org/10.1002/path.1711500206

    Article  CAS  PubMed  Google Scholar 

  29. Yamaji K, Suzuki Y, Suzuki H, Satake K, Horikoshi S, Novak J, Tomino Y (2014) The kinetics of glomerular deposition of nephritogenic IgA. PLoS One 9:e113005. https://doi.org/10.1371/journal.pone.0113005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cambier A, Rabant M, Peuchmaur M, Hertig A, Deschenes G, Couchoud C, Kolko A, Salomon R, Hogan J, Robert T (2018) Immunosuppressive treatment in children with IgA nephropathy and the clinical value of podocytopathic features. Kidney Int Rep 3:916–925. https://doi.org/10.1016/j.ekir.2018.03.013

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cambier A, Boyer O, Deschenes G, Gleeson J, Couderc A, Hogan J, Robert T (2019) Steroid therapy in children with IgA nephropathy. Pediatr Nephrol. https://doi.org/10.1007/s00467-018-4189-7

  32. Reich HN, Troyanov S, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry (2007) Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 18:3177–3183. https://doi.org/10.1681/ASN.2007050526

    Article  CAS  PubMed  Google Scholar 

  33. Segarra A, Romero K, Agraz I, Ramos N, Madrid A, Carnicer C, Jatem E, Vilalta R, Lara LE, Ostos E, Valtierra N, Jaramillo J, Arredondo KV, Ariceta G, Martinez C (2018) Mesangial C4d deposits in early IgA nephropathy. Clin J Am Soc Nephrol 13:258–264. https://doi.org/10.2215/CJN.02530317

    Article  CAS  PubMed  Google Scholar 

  34. Trimarchi H, Coppo R (2019) Glomerular endothelial activation, C4d deposits and microangiopathy in immunoglobulin A nephropathy. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfz241

  35. Sato Y, Sasaki S, Okamoto T, Takahashi T, Hayashi A, Ogawa Y, Ariga T (2019) Mesangial C4d deposition at diagnosis in childhood immunoglobulin A nephropathy. Pediatr Int 61:1133–1139. https://doi.org/10.1111/ped.13921

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all participants and attending physicians for their contributions. We thank Richard Robins, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Wakayama Medical University, Wakayama City, Wakayama, Japan

    Yuko Shima, Hironobu Mukaiyama, Yu Tanaka & Takuzo Wada

  2. Department of Pediatrics, Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, 207 Uehara Nishihara-cho, Nakagami-gun, Okinawa, 903-0125, Japan

    Koichi Nakanishi

  3. Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Hyogo, Japan

    Ryojiro Tanaka & Hiroshi Kaito

  4. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Kandai Nozu & Kazumoto Iijima

  5. Division for Clinical Trials, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan

    Mayumi Sako

  6. Clinical Research Center, Takatsuki General Hospital, Takatsuki City, Osaka, Japan

    Norishige Yoshikawa

Authors
  1. Yuko Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koichi Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hironobu Mukaiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takuzo Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryojiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroshi Kaito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kandai Nozu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mayumi Sako
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kazumoto Iijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Norishige Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS and KN contributed to study conception and design. Material preparation and data collection were performed by all authors. YS and NY performed pathological evaluations. Data analysis was performed by YS and KN. The first draft of the manuscript was written by YS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Koichi Nakanishi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Wakayama Medical University) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Formal consent is not required for this type of study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shima, Y., Nakanishi, K., Mukaiyama, H. et al. Clinicopathological significance of glomerular capillary IgA deposition in childhood IgA nephropathy. Pediatr Nephrol 36, 899–908 (2021). https://doi.org/10.1007/s00467-020-04772-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-020-04772-4

Keywords

Search

Navigation