Top

Open Access 25-04-2024 | Glomerulonephritis | Original Article

Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children

Authors: Chika Ueda, Tomoko Horinouchi, Yuta Inoki, Yuta Ichikawa, Yu Tanaka, Hideaki Kitakado, Atsushi Kondo, Nana Sakakibara, China Nagano, Tomohiko Yamamura, Junya Fujimura, Naohiro Kamiyoshi, Shingo Ishimori, Takeshi Ninchoji, Hiroshi Kaito, Yuko Shima, Kazumoto Iijima, Kandai Nozu, Norishige Yoshikawa

Published in: Pediatric Nephrology

Abstract

Background

Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses.

Methods

In this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients.

Results

Out of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5–8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m². Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up.

Conclusions

Most patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis.

Graphical abstract

Available only for authorised users

Habib R, Kleinknecht C, Gubler MC, Levy M (1973) Idiopathic membranoproliferative glomerulonephritis in children. Report of 105 cases. Clin Nephrol 1:194–214PubMed

Anders D, Agricola B, Sippel M, Thoenes W (1977) Basement membrane changes in membranoproliferative glomerulonephritis. II. Characterization of a third type by silver impregnation of ultra thin sections. Virchows Arch A Pathol Anat Histol 376:1–19. https://doi.org/10.1007/BF00433081CrossRefPubMed

Burkholder PM, Marchand A, Krueger RP (1970) Mixed membranous and proliferative glomerulonephritis. A correlative light, immunofluorescence, and electron microscopic study. Lab Invest 23:459–479PubMed

Appel GB, Cook HT, Hageman G, Jennette JC, Kashgarian M, Kirschfink M, Lambris JD, Lanning L, Lutz HU, Meri S, Rose NR, Salant DJ, Sethi S, Smith RJ, Smoyer W, Tully HF, Tully SP, Walker P, Welsh M, Wurzner R, Zipfel PF (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol 16:1392–1403. https://doi.org/10.1681/ASN.2005010078CrossRefPubMed

Sethi S, Fervenza FC (2012) Membranoproliferative glomerulonephritis–a new look at an old entity. N Engl J Med 366:1119–1131. https://doi.org/10.1056/NEJMra1108178CrossRefPubMed

Bomback AS, Appel GB (2012) Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 8:634–642. https://doi.org/10.1038/nrneph.2012.213CrossRefPubMed

Kirpalani A, Jawa N, Smoyer WE, Licht C; Midwest Pediatric Nephrology Consortium (2020) Long-Term Outcomes of C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis in Children. Kidney Int Rep 5:2313–2324. https://doi.org/10.1016/j.ekir.2020.09.019CrossRef

Licht C, Vivarelli M, Riedl Khursigara M, Pickering MC, Walker PD (2021) Membranoproliferative Glomerulonephritis and C3 Glomerulopathy in Children. In: Emma F, Goldstein S L, Bagga A, Bates C M, Shroff R (ed) Pediatric Nephrology, 8th edn. Springer Nature, Cham, pp 563–593. https://doi.org/10.1007/978-3-030-52719-8

Pickering MC, D’Agati VD, Nester CM, Smith RJ, Haas M, Appel GB, Alpers CE, Bajema IM, Bedrosian C, Braun M, Doyle M, Fakhouri F, Fervenza FC, Fogo AB, Fremeaux-Bacchi V, Gale DP, Goicoechea de Jorge E, Griffin G, Harris CL, Holers VM, Johnson S, Lavin PJ, Medjeral-Thomas N, Paul Morgan B, Nast CC, Noel LH, Peters DK, Rodriguez de Cordoba S, Servais A, Sethi S, Song WC, Tamburini P, Thurman JM, Zavros M, Cook HT (2013) C3 glomerulopathy: consensus report. Kidney Int 84:1079–1089. https://doi.org/10.1038/ki.2013.377CrossRefPubMedPubMedCentral

10.

Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2014) Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol 18:626–633. https://doi.org/10.1007/s10157-013-0856-yCrossRefPubMed

11.

Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992. https://doi.org/10.1053/j.ajkd.2008.12.034CrossRefPubMed

12.

Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244CrossRefPubMed

13.

Khandelwal P, Bhardwaj S, Singh G, Sinha A, Hari P, Bagga A (2021) Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis. Pediatr Nephrol 36:591–600. https://doi.org/10.1007/s00467-020-04736-8CrossRefPubMed

14.

Wong EKS, Marchbank KJ, Lomax-Browne H, Pappworth IY, Denton H, Cooke K, Ward S, McLoughlin AC, Richardson G, Wilson V, Harris CL, Morgan BP, Hakobyan S, McAlinden P, Gale DP, Maxwell H, Christian M, Malcomson R, Goodship THJ, Marks SD, Pickering MC, Kavanagh D, Cook HT, Johnson SA; MPGN/DDD/C3 Glomerulopathy Rare Disease Group and National Study of MPGN/DDD/C3 Glomerulopathy Investigators (2021) C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes. Clin J Am Soc Nephrol 16:1639–1651. https://doi.org/10.2215/CJN.00320121CrossRef

15.

Iatropoulos P, Noris M, Mele C, Piras R, Valoti E, Bresin E, Curreri M, Mondo E, Zito A, Gamba S, Bettoni S, Murer L, Fremeaux-Bacchi V, Vivarelli M, Emma F, Daina E, Remuzzi G (2016) Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome. Mol Immunol 71:131–142. https://doi.org/10.1016/j.molimm.2016.01.010CrossRefPubMed

16.

Servais A, Noel LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grunfeld JP, Niaudet P, Lesavre P, Fremeaux-Bacchi V (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82:454–464. https://doi.org/10.1038/ki.2012.63CrossRefPubMed

17.

Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, Bresin E, Gamba S, Alberti M, Breno M, Perna A, Bettoni S, Sabadini E, Murer L, Vivarelli M, Noris M, Remuzzi G, Registry of Membranoproliferative Glomerulonephritis, C3 Glomerulopathy; Nastasi (2018) Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN. J Am Soc Nephrol 29:283–294. https://doi.org/10.1681/ASN.2017030258CrossRefPubMed

18.

Somers M, Kertesz S, Rosen S, Herrin J, Colvin R, Palacios de Carreta N, Kim M (1995) Non-nephrotic children with membranoproliferative glomerulonephritis: are steroids indicated? Pediatr Nephrol 9:140–144. https://doi.org/10.1007/BF00860727CrossRefPubMed

19.

Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrishnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D’Agati VD, Appel GB (2018) C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int 93:977–985. https://doi.org/10.1016/j.kint.2017.10.022CrossRefPubMed

20.

Bennett WM, Fassett RG, Walker RG, Fairley KF, d’Apice AJ, Kincaid-Smith P (1989) Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease. Am J Kidney Dis 13:469–476. https://doi.org/10.1016/s0272-6386(89)80004-6CrossRefPubMed

21.

Cameron JS, Turner DR, Heaton J, Williams DG, Ogg CS, Chantler C, Haycock GB, Hicks J (1983) Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long-term prognosis. Am J Med 74:175–192. https://doi.org/10.1016/0002-9343(83)90606-xCrossRefPubMed

22.

Little MA, Dupont P, Campbell E, Dorman A, Walshe JJ (2006) Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk. Kidney Int 69:504–511. https://doi.org/10.1038/sj.ki.5000084CrossRefPubMed

23.

Lomax-Browne HJ, Medjeral-Thomas NR, Barbour SJ, Gisby J, Han H, Bomback AS, Fervenza FC, Cairns TH, Szydlo R, Tan SJ, Marks SD, Waters AM, Appel GB, D’Agati VD, Sethi S, Nast CC, Bajema I, Alpers CE, Fogo AB, Licht C, Fakhouri F, Cattran DC, Peters JE, Cook HT, Pickering MC (2022) Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis. Clin J Am Soc Nephrol 17:994–1007. https://doi.org/10.2215/CJN.16801221CrossRefPubMedPubMedCentral

24.

Okuda Y, Ishikura K, Hamada R, Harada R, Sakai T, Hamasaki Y, Hataya H, Fukuzawa R, Ogata K, Honda M (2015) Membranoproliferative glomerulonephritis and C3 glomerulonephritis: frequency, clinical features, and outcome in children. Nephrology (Carlton) 20:286–292. https://doi.org/10.1111/nep.12382CrossRefPubMed

25.

Avasare RS, Canetta PA, Bomback AS, Marasa M, Caliskan Y, Ozluk Y, Li Y, Gharavi AG, Appel GB (2018) Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series. Clin J Am Soc Nephrol 13:406–413. https://doi.org/10.2215/CJN.09080817CrossRefPubMedPubMedCentral

26.

Caravaca-Fontan F, Diaz-Encarnacion MM, Lucientes L, Cavero T, Cabello V, Ariceta G, Quintana LF, Marco H, Barros X, Ramos N, Rodriguez-Mendiola N, Cruz S, Fernandez-Juarez G, Rodriguez A, Perez de Jose A, Rabasco C, Rodado R, Fernandez L, Perez Gomez V, Avila AI, Bravo L, Lumbreras J, Allende N, Sanchez de la Nieta MD, Rodriguez E, Olea T, Melgosa M, Huerta A, Miquel R, Mon C, Fraga G, de Lorenzo A, Draibe J, Cano-Megias M, Gonzalez F, Shabaka A, Lopez-Rubio ME, Fenollosa MA, Martin-Penagos L, Da Silva I, Alonso Titos J, Rodriguez de Cordoba S, Goicoechea de Jorge E, Praga M; Spanish Group for the Study of Glomerular Diseases GLOSEN (2020) Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease. Clin J Am Soc Nephrol 15:1287–1298. https://doi.org/10.2215/CJN.15241219CrossRef

27.

Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, Nasr SH, Smith RJ (2013) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83:293–299. https://doi.org/10.1038/ki.2012.384CrossRefPubMed

Title: Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children
Authors: Chika Ueda
Tomoko Horinouchi
Yuta Inoki
Yuta Ichikawa
Yu Tanaka
Hideaki Kitakado
Atsushi Kondo
Nana Sakakibara
China Nagano
Tomohiko Yamamura
Junya Fujimura
Naohiro Kamiyoshi
Shingo Ishimori
Takeshi Ninchoji
Hiroshi Kaito
Yuko Shima
Kazumoto Iijima
Kandai Nozu
Norishige Yoshikawa
Publication date: 25-04-2024
Publisher: Springer Berlin Heidelberg
Keywords: Glomerulonephritis
Prednisolone
Nephrotic Syndrome
Published in: Pediatric Nephrology
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-024-06377-7

At a glance: The STEP trials

Springer Medicine

Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

Please log in to get access to this content