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Primary membranous nephropathy in children and adolescents: a single-centre report from South Asia

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Abstract

Background

Unlike adults, primary membranous nephropathy (PMN) comprises only 1–2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome.

Methods

This prospective study includes children and adolescents (< 20 years) with biopsy-proven PMN without secondary causes. Anti-PLA2R assessment: before and after completing therapy. Outcome: percentage of patients achieving remission.

Results

Study cohort included 48 (M:F ratio 1.1:1) patients and median age 17 (IQR 15–18) years, with 35 (72.9%) PLA2R related. Median interval from symptom onset to presentation was 5 months, where median proteinuria, serum albumin and creatinine were 4.9 g/day, 2.1 g/dL and 0.63 mg/dL, respectively. Forty-seven patients received immunosuppressive therapy, with various agents used as first-line therapy: cyclical CYC/GC (53.1%), CNI/GC (21.3%), rituximab (14.9%), prednisolone alone (4.3%), azathioprine (4.3%) and mycophenolate mofetil (2.1%). Median follow-up was 29 (14, 59) months. At 6 months, 11 (24.4%) and 17 (37.7%) had complete remission (CR) or partial remission (PR), while at last follow-up (median 29 months), 20 (45.4%) and 14 (31.8%) had CR and PR respectively. No significant differences in outcome were observed with different agents. A total of 60% patients treated with rituximab as first line/for relapsing disease, and all cases with resistant disease receiving rituximab had CR or PR at last follow-up. PLA2R antibody presence was associated with clinical outcome.

Conclusions

Three-quarters of PMN in children and adolescents is PLA2R related and two-thirds respond to immunosuppressive therapy. Rituximab is a promising agent to manage PMN in children. Anti-PLA2R is associated with clinical outcomes.

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Data availability

All relevant data will be available from the corresponding author and will be reproduced on demand.

References

  1. Safar-Boueri L, Piya A, Beck LH Jr, Ayalon R (2019) Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. Pediatr Nephrol. https://doi.org/10.1007/s00467-019-04425-1

  2. (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165

  3. Kleinknecht C, Levy M, Gagnadoux MF, Habib R (1979) Membranous glomerulonephritis with extra-renal disorders in children. Medicine 58:219–228

    Article  CAS  Google Scholar 

  4. Lee BH, Cho HY, Kang HG, Ha IS, Cheong HI, Moon KC, Lim IS, Choi Y (2006) Idiopathic membranous nephropathy in children. Pediatr Nephrol 21:1707–1715

    Article  Google Scholar 

  5. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS, Debayle D, Merchant M, Klein J, Salant DJ, Stahl R, Lambeau G (2014) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287

    Article  Google Scholar 

  6. Debiec H, Lefeu F, Kemper MJ, Niaudet P, Deschênes G, Remuzzi G, Ulinski T, Ronco P (2011) Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med 364:2101–2110

    Article  CAS  Google Scholar 

  7. Dai H, Zhang H, He Y (2015) Diagnostic accuracy of PLA2R autoantibodies and glomerular staining for the differentiation of idiopathic and secondary membranous nephropathy: an updated meta-analysis. Sci Rep 5:8803

    Article  CAS  Google Scholar 

  8. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ (2011) Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6:1286–1291

    Article  CAS  Google Scholar 

  9. Cossey LN, Walker PD, Larsen CP (2013) Phospholipase A2 receptor staining in pediatric idiopathic membranous glomerulopathy. Pediatr Nephrol 28:2307–2311

    Article  Google Scholar 

  10. Zhang D, Wu Y, Zhang C, Zhang W, Zou J, Jiang G (2019) Compared staining of the phospholipase A2 receptor in the glomeruli of Chinese adults and children with idiopathic membranous nephropathy. Pathol Res Pract 215:952–956

    Article  CAS  Google Scholar 

  11. Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, Deschênes G, Ronco PM (2002) Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med 346:2053–2060

    Article  Google Scholar 

  12. Dettmar AK, Wiech T, Kemper MJ, Soave A, Rink M, Oh J, Stahl R, Hoxha E, Pediatric MN Study Group (2018) Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents. Pediatr Nephrol 33:463–472

    Article  Google Scholar 

  13. Kumar V, Ramachandran R, Kumar A, Nada R, Suri D, Gupta A, Kohli HS, Gupta KL, Jha V (2015) Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy. Nephrology 20:572–575

    Article  CAS  Google Scholar 

  14. Kumar V, Varma AK, Nada R, Ghosh R, Suri D, Gupta A, Kumar V, Rathi M, Kohli H, Jha V, Gupta K, Ramachandran R (2017) Primary membranous nephropathy in adolescence: a prospective study. Nephrology 22:678–683

    Article  CAS  Google Scholar 

  15. Ramachandran R, Yadav AK, Kumar V, Siva Tez Pinnamaneni V, Nada R, Ghosh R, Kumar V, Rathi M, Kohli HS, Gupta KL, Sakhuja V, Jha V (2017) Two-year follow-up study of membranous nephropathy treated with tacrolimus and corticosteroids versus cyclical corticosteroids and cyclophosphamide. Kidney Int Rep 2:610–616

    Article  Google Scholar 

  16. Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA, Aslam N, Jefferson JA, Gipson PE, Rizk DV, Sedor JR, Simon JF, McCarthy ET, Brenchley P, Sethi S, Avila-Casado C, Beanlands H, Lieske JC, Philibert D, Li T, Thomas LF, MENTOR Investigators (2019) Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med 381:36–46

  17. Ramachandran R, Kumar V, Rathi M, Nada R, Jha V, Gupta KL, Sakhuja V, Kohli HS (2014) Tacrolimus therapy in adult-onset steroid-resistant nephrotic syndrome due to a focal segmental glomerulosclerosis single-center experience. Nephrol Dial Transplant 29:1918–1924

    Article  CAS  Google Scholar 

  18. Cattran DC, Feehally J, Cook HT, Liu ZH, Fervenza FC, Mezzano SA, Floege J, Nachman PH, Gipson DS, Praga M, Glassock RJ, Radhakrishnan J, Hodson EM, Rovin BH, Jha V, Troyanov S, Li PKT, Wetzels JFM (2012) Kidney disease: improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2(2):139–274

    Article  Google Scholar 

  19. Ramachandran R, Kumar V, Kumar A, Yadav AK, Nada R, Kumar H, Kumar V, Rathi M, Kohli HS, Gupta KL, Sakhuja V, Jha V (2016) PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in south Asians. Nephrol Dial Transplant 31:1486–1493

    Article  CAS  Google Scholar 

  20. Inaguma Y, Shiratori A, Nakagawa T, Kanda K, Yoshida M, Hara S, Kaito H, Nozu K, Iijima K, Yoshikawa N, Tanaka R (2019) M-type phospholipase A2 receptor staining in children with idiopathic membranous nephropathy: PLA2R staining in children with IMN. Open Urol Nephrol J 12:27–32

    Article  Google Scholar 

  21. Kanda S, Horita S, Yanagihara T, Shimizu A, Hattori M (2017) M-type phospholipase A2 receptor (PLA2R) glomerular staining in pediatric idiopathic membranous nephropathy. Pediatr Nephrol 32:713–717

    Article  Google Scholar 

  22. Wang J, Cui Z, Lu J, Probst C, Zhang YM, Wang X, Qu Z, Wang F, Meng LQ, Cheng XY, Liu G, Debiec H, Ronco P, Zhao MH (2017) Circulating antibodies against thrombospondin type-I domain-containing 7A in Chinese patients with idiopathic membranous nephropathy. Clin J Am Soc Nephrol 12:1642–1651

    Article  CAS  Google Scholar 

  23. Valentini RP, Mattoo TK, Kapur G, Imam A (2009) Membranous glomerulonephritis: treatment response and outcome in children. Pediatr Nephrol 24:301–308

    Article  Google Scholar 

  24. O’Shaughnessy MM, Troost JP, Bomback AS, Hladunewich MA, Ashoor IF, Gibson KL, Matar RB, Selewski DT, Srivastava T, Rheault MN, Al-Uzri A, Kogon AJ, Khalid M, Vento S, Sanghani NS, Gillespie BW, Gipson DS, Wang CS, Parsa A, Guay-Woodford L, Laurin LP (2019) Treatment patterns among adults and children with membranous nephropathy in the cure glomerulonephropathy network (CureGN). Kidney Int Rep 4:1725–1734

    Article  Google Scholar 

  25. Chen A, Frank R, Vento S, Crosby V, Chandra M, Gauthier B, Valderrama E, Trachtman H (2007) Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome. BMC Nephrol 8:11

    Article  Google Scholar 

  26. Bhimma R, Naicker E, Ramdial PK (2013) Mycophenolate mofetil therapy in children with idiopathic membranous nephropathy. Clin Nephrol 80:441–448

    Article  CAS  Google Scholar 

  27. Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P (2002) Rituximab for idiopathic membranous nephropathy. Lancet 360:923–924

    Article  CAS  Google Scholar 

  28. Zhu B, Huang J (2011) Successful treatment and clearing of circulating CD19-positive cells by rituximab in a child with idiopathic membranous nephropathy. Pediatr Nephrol 26:637–638

    Article  Google Scholar 

  29. Malatesta-Muncher R, Eldin KW, Beck LH Jr, Michael M (2018) Idiopathic membranous nephropathy in children treated with rituximab: report of two cases. Pediatr Nephrol 33:1089–1092

    Article  Google Scholar 

  30. Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasà M, Remuzzi G (2012) Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 23:1416–1425

    Article  CAS  Google Scholar 

  31. Fervenza FC, Abraham RS, Erickson SB, Irazabal MV, Eirin A, Specks U, Nachman PH, Bergstralh EJ, Leung N, Cosio FG, Hogan MC, Dillon JJ, Hickson LJ, Li X, Cattran DC, Mayo Nephrology Collaborative Group (2010) Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol 5:2188–2198

    Article  CAS  Google Scholar 

  32. Cravedi P, Ruggenenti P, Sghirlanzoni MC, Remuzzi G (2007) Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2:932–937

    Article  CAS  Google Scholar 

  33. Ramachandran R, Kumar V, Nada R, Jha V (2015) Serial monitoring of anti-PLA2R in initial PLA2R-negative patients with primary membranous nephropathy. Kidney Int 88:1198–1199

    Article  CAS  Google Scholar 

Download references

Funding

The authors received financial support from the Indian Council of Medical Research funding no. 2013–2973. RR received intramural funds from the PGIMER, Chandigarh.

Author information

Author notes

  1. Raja Ramachandran and Saurabh Nayak have equal contribution as the 1st author

Authors and Affiliations

  1. Department of Nephrology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

    Raja Ramachandran, Saurabh Nayak, Neha Agrawal, Ritika Bansal, Manish Rathi & Harbir Singh Kohli

  2. Department of Dermatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

    Vinod Kumar

  3. Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

    Ashwani Kumar & Ritambhra Nada

  4. Division of Pediatric Nephrology, Department of Paediatrics, Postgraduate Institute of Medical Education & Research, Chandigarh, India

    Karalanglin Tiewsoh

Authors
  1. Raja Ramachandran
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Contributions

RR conceptualized the study, collected the data, analyzed results and helped in writing manuscript. SN helped in data collection and manuscript writing. NA, RB, KL, MR and HSK helped in data collection. VK helped in statistics and result analysis. AK and RN performed serum PLA2R and tissue level testing respectively.

Corresponding author

Correspondence to Raja Ramachandran.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Institutional Ethic committee (PGI/IEC/2014/241).

Consent of participation

Written informed consent for participation was taken from all the patients and parents in case of age < 18 years.

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All authors have approved the manuscript for publication.

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Ramachandran, R., Nayak, S., Kumar, V. et al. Primary membranous nephropathy in children and adolescents: a single-centre report from South Asia. Pediatr Nephrol 36, 1217–1226 (2021). https://doi.org/10.1007/s00467-020-04798-8

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  • DOI: https://doi.org/10.1007/s00467-020-04798-8

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