Skip to main content

Advertisement

SpringerLink
Log in

Crescentic IgA nephropathy in children

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

Abstract

Objectives

Crescentic IgA nephropathy (C-IgAN) is defined as IgAN with more than 50% of glomeruli showing crescents. C-IgAN in children is rare; we investigate in detail for the first time.

Methods

We retrospectively analyzed the 515 consecutive children who were newly diagnosed with biopsy-proven IgAN between June 1976 and May 2010. We compared clinical and pathological findings between C-IgAN and non-C-IgAN.

Results

Among 515 cases of childhood IgAN, 25 children (4.9%) had C-IgAN. Of these 25, 16 children (64%) were referred to hospitals by annual school screening. Clinical findings showed significant differences in gross hematuria (76 vs. 50%, p = .03), excretion of proteinuria (1.9 vs. 0.5 g/day/m2, p < .0001), eGFR (102 vs. 108 ml/min/1.73 m2, p = .03), and duration from onset to renal biopsy (4.0 vs. 8.0 months, p = .04) between groups. Pathological findings showed significant differences in M1 (88 vs. 55%, p = .02), E1 (83 vs. 53%, p = .008), and presence of tubular atrophy/interstitial fibrosis (88 vs. 53%, p < .0001) between groups. The 16 children with C-IgAN were treated with prednisolone and immunosuppressant. Four cases (16%) reached chronic renal failure (eGFR < 60) at the latest observation (mean observation period: 6.0 ± 3.6 years). Patients with C-IgAN had significantly lower renal survival curve than non-C-IgAN patients according to Kaplan-Meier analysis (77.1% vs. 92.6% at 13 years, p < .0001). Compared with previous reports, however, they had better renal outcome.

Conclusions

We confirmed the importance of school screening to find C-IgAN. Although most crescents (mean: 98.1%) of C-IgAN were cellular/fibrocellular, and acute lesions were well modified with combination therapy, the presence of tubular atrophy in C-IgAN may be the reason for poorer prognosis.

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

    Article  CAS  Google Scholar 

  2. Alexopoulos E (2004) Treatment of primary IgA nephropathy. Kidney Int 65:341–355

    Article  Google Scholar 

  3. Shima Y, Nakanishi K, Yoshikawa N (2013) Spontaneous remission in children with IgA nephropathy. Pediatr Nephrol 28:71–76

    Article  Google Scholar 

  4. Yoshikawa N, Ito H, Nakamura H (1992) Prognostic indicators in childhood IgA nephropathy. Nephron 60:60–67

    Article  CAS  Google Scholar 

  5. Abe T, Kida H, Yoshimura M, Yokoyama H, Koshino Y, Tomosugi N, Hattori N (1986) Participation of extracapillary lesions (ECL) in progression of IgA nephropathy. Clin Nephrol 25:37–41

    PubMed  CAS  Google Scholar 

  6. Ballardie FW, Roberts IS (2002) Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 13:142–148

    PubMed  CAS  Google Scholar 

  7. Tang Z, Wu Y, Wang QW, Yu YS, Hu WX, Yao XD, Chen HP, Liu ZH, Li LS (2002) Idiopathic IgA nephropathy with diffuse crescent formation. Am J Nephrol 22:480–486

    Article  Google Scholar 

  8. Tumlin JA, Lohavichan V, Hennigar R (2003) Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant 18:1321–1329

    Article  CAS  Google Scholar 

  9. Lv J, Yang Y, Zhang H, Chen W, Pan X, Guo Z, Wang C, Li S, Zhang J, Zhang J, Liu L, Shi S, Wang S, Chen M, Cui Z, Chen N, Yu X, Zhao M, Wang H (2013) Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study. J Am Soc Nephrol 24:2118–2125

    Article  CAS  Google Scholar 

  10. 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  Google Scholar 

  11. 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

    Article  Google Scholar 

  12. 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

    Article  Google Scholar 

  13. 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

    Article  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  CAS  Google Scholar 

  16. No authors listed (2013) Chapter 1: Difinition and classification of CKD. KDIGO 2012 clinical practice guideline for the evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 3:19–62

    Article  Google Scholar 

  17. 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

    Article  CAS  Google Scholar 

  18. Murakami M, Hayakawa M, Yanagihara T, Hukunaga Y (2005) Proteinuria screening for children. Kidney Int Suppl 94:S23–S27

    Article  Google Scholar 

  19. Churg J, Bernstein J, Glassock RJ (1995) Renal disease: classification and atlas of glomerular diseases, 2nd edn. Igaku-shoin Medical Publishers, Tokyo, pp 86–88

    Google Scholar 

  20. Yata N, Nakanishi K, Shima Y, Togawa H, Obana M, Sako M, Nozu K, Tanaka R, Iijima K, Yoshikawa N (2008) Improved renal survival in Japanese children with IgA nephropathy. Pediatr Nephrol 23:905–912

    Article  Google Scholar 

  21. Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The angiotensin-converting-enzyme inhibition in progressive renal insufficiency study group. N Engl J Med 334:939–945

    Article  CAS  Google Scholar 

  22. The GISEN Group (1997) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349:1857–1863

    Article  Google Scholar 

  23. Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G (1999) Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 354:359–364

    Article  CAS  Google Scholar 

  24. Maschio G, Cagnoli L, Claroni F, Fusaroli M, Rugiu C, Sanna G, Sasdelli M, Zuccalà A, Zucchelli P (1994) ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant 9:265–269

    PubMed  CAS  Google Scholar 

  25. Praga M, Gutiérrez E, González E, Morales E, Hernández E (2003) Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 14:1578–1583

    Article  CAS  Google Scholar 

  26. Coppo R, Peruzzi L, Amore A, Piccoli A, Cochat P, Stone R, Kirschstein M, Linné T (2007) IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol 18:1880–1888

    Article  CAS  Google Scholar 

  27. Nakanishi K, Iijima K, Ishikura K, Hataya H, Awazu M, Sako M, Honda M, Yoshikawa N, Japanese Pediatric IgA Nephropathy Treatment Study Group (2009) Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study. Pediatr Nephrol 24:845–849

    Article  Google Scholar 

  28. Shima Y, Nakanishi K, Sako M, Saito-Oba M, Hamasaki Y, Hataya H, Honda M, Kamei K, Ishikura K, Ito S, Kaito H, Tanaka R, Nozu K, Nakamura H, Ohashi Y, Iijima K, Yoshikawa N, Japanese Study Group of Kidney Disease in Children (JSKDC) (2019) Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol 34:837–846

    Article  Google Scholar 

  29. 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

    Article  Google Scholar 

  30. 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

  31. 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

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all of the participants and attending physicians for their contributions. We also acknowledge proofreading and editing by Benjamin Phillis at the Clinical Study Support Center at the Wakayama Medical University Hospital.

Author information

Authors and Affiliations

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

    Yuko Shima, Taketsugu Hama, Hironobu Mukaiyama, Masashi Sato & Yu Tanaka

  2. Department of 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, Wakayama Medical University, Wakayama City, Wakayama, 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. Taketsugu Hama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hironobu Mukaiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masashi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ryojiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroshi Kaito
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kandai Nozu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mayumi Sako
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazumoto Iijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Norishige Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS and KN contributed to the 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., Hama, T. et al. Crescentic IgA nephropathy in children. Pediatr Nephrol 35, 1005–1014 (2020). https://doi.org/10.1007/s00467-020-04483-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-020-04483-w

Keywords

Search

Navigation