{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:03:05Z","timestamp":1760151785294,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Therapy of immune-mediated kidney diseases has evolved during recent decades from the non-specific use of corticosteroids and antiproliferative agents (like cyclophosphamide or azathioprine), towards the use of more specific drugs with measurable pharmacokinetics, like calcineurin inhibitors (cyclosporine A and tacrolimus) and mycophenolate mofetil, to the treatment with biologic drugs targeting detailed specific receptors, like rituximab, eculizumab or abatacept. Moreover, the data coming from a molecular science revealed that several drugs, which have been previously used exclusively to modify the upregulated adaptive immune system, may also exert a local effect on the kidney microstructure and ameliorate the functional instability of podocytes, reducing the leak of protein into the urinary space. The innate immune system also became a target of new therapies, as its specific role in different kidney diseases has been de novo defined. Current therapy of several immune kidney diseases may now be personalized, based on the detailed diagnostic procedures, including molecular tests. However, in most cases there is still a space for standard therapies based on variable protocols including usage of steroids with the steroid-sparing agents. They are used as a first-line treatment, while modern biologic agents are selected as further steps in cases of lack of the efficacy or toxicity of the basic therapies. In several clinical settings, the biologic drugs are effective as the add-on therapy.<\/jats:p>","DOI":"10.3390\/children9040536","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Second and Third Generational Advances in Therapies of the Immune-Mediated Kidney Diseases in Children and Adolescents"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6814-6589","authenticated-orcid":false,"given":"Ryszard","family":"Grenda","sequence":"first","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Hypertension, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-8643","authenticated-orcid":false,"given":"\u0141ukasz","family":"Obrycki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Hypertension, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ki.2014.260","article-title":"A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment","volume":"87","author":"Yoshikawa","year":"2015","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00467-012-2310-x","article-title":"Treatment of steroid-sensitive nephrotic syndrome: New guidelines from KDIGO","volume":"28","author":"Lombel","year":"2012","journal-title":"Pediatric Nephrol."},{"key":"ref_4","first-page":"CD011129","article-title":"Early palliative care for adults with advanced cancer","volume":"6","author":"Haun","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.2215\/CJN.01120905","article-title":"Steroid Treatment for Severe Childhood IgA Nephropathy: A Randomized, Controlled Trial","volume":"1","author":"Yoshikawa","year":"2006","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2165\/00003088-199120030-00002","article-title":"Clinical Pharmacokinetics of Cyclophosphamide","volume":"20","author":"Moore","year":"1991","journal-title":"Clin. Pharmacokinet."},{"key":"ref_7","first-page":"170","article-title":"Efficacy of Cyclophosphamide in Steroid-Sensitive Childhood Nephrotic Syndrome with Different Morphological Lesions","volume":"41","author":"Tejani","year":"1985","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00467-011-1825-x","article-title":"Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome","volume":"26","author":"Zagury","year":"2011","journal-title":"Pediatric Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.2215\/CJN.08630910","article-title":"Long-Term Results of a Randomized Controlled Trial in Childhood IgA Nephropathy","volume":"6","author":"Kamei","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/00007890-199510150-00003","article-title":"Monitoring of azathioprine-induced immunosuppression with thiopurine methyltransferase activity in kidney transplant recipients","volume":"60","author":"Mircheva","year":"1995","journal-title":"Transplantation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1007\/s00467-008-0794-1","article-title":"Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome\u2014A randomized controlled multicentre trial by the Arbeitsgemeinschaft f\u00fcr P\u00e4diatrische Nephrologie","volume":"23","author":"Plank","year":"2008","journal-title":"Pediatric Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/ndt\/gfh066","article-title":"Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome","volume":"19","author":"Kemper","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1053\/j.ajkd.2008.11.033","article-title":"Efficacy and Safety of Tacrolimus Versus Cyclosporine in Children with Steroid-Resistant Nephrotic Syndrome: A Randomized Controlled Trial","volume":"53","author":"Choudhry","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1007\/s00467-015-3133-3","article-title":"Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome","volume":"30","author":"Jahan","year":"2015","journal-title":"Pediatric Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s12519-015-0062-y","article-title":"Tacrolimus for children with refractory nephrotic syndrome: A one-year prospective, multicenter, and open-label study of Tacrobell\u00ae, a generic formula","volume":"12","author":"Yang","year":"2015","journal-title":"World J. Pediatric"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1007\/s00467-008-0899-6","article-title":"Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome","volume":"23","author":"Dorresteijn","year":"2008","journal-title":"Pediatric Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1681\/ASN.2012121200","article-title":"Mycophenolate Mofetil versus Cyclosporin A in Children with Frequently Relapsing Nephrotic Syndrome","volume":"24","author":"Gellermann","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1007\/s00467-017-3780-7","article-title":"Difficult-to-treat idiopathic nephrotic syndrome: Established drugs, open questions and future options","volume":"33","author":"Kemper","year":"2017","journal-title":"Pediatric Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"761600","DOI":"10.3389\/fmed.2021.761600","article-title":"Molecular Mechanisms of Proteinuria in Minimal Change Disease","volume":"8","author":"Purohit","year":"2021","journal-title":"Front. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1007\/s00467-017-3746-9","article-title":"Rituximab in steroid-sensitive nephrotic syndrome: Lessons from clinical trials","volume":"33","author":"Iijima","year":"2017","journal-title":"Pediatric Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1136\/archdischild-2020-321211","article-title":"Use of rituximab in paediatric nephrology","volume":"106","author":"Sinha","year":"2021","journal-title":"Arch. Dis. Child."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Salvadori, M., and Tsalouchos, A. (2021). How immunosuppressive drugs may directly target podocytes in glomerular diseases. Pediatric Nephrol., 1\u201311.","DOI":"10.1007\/s00467-021-05196-4"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85ra46","DOI":"10.1126\/scitranslmed.3002231","article-title":"Rituximab Targets Podocytes in Recurrent Focal Segmental Glomerulosclerosis","volume":"3","author":"Fornoni","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1053\/j.seminhematol.2010.01.011","article-title":"Rituximab: Mechanism of Action","volume":"47","author":"Weiner","year":"2010","journal-title":"Semin. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.3389\/fimmu.2019.01653","article-title":"Prolonged Impairment of Immunological Memory After Anti-CD20 Treatment in Pediatric Idiopathic Nephrotic Syndrome","volume":"10","author":"Colucci","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00431-016-2747-1","article-title":"Rituximab is not a \u201cmagic drug\u201d in post-transplant recurrence of nephrotic syndrome","volume":"175","author":"Grenda","year":"2016","journal-title":"Eur. J. Pediatric"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5414\/CN110134","article-title":"Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies","volume":"94","author":"Hansrivijit","year":"2020","journal-title":"Clin. Nephrol."},{"key":"ref_28","first-page":"570","article-title":"Improving Clinical Trials for Anticomplement Therapies in Complement-Mediated Glomerulopathies: Report of a Scientific Workshop Sponsored by the National Kidney Foundation","volume":"71","author":"Bomback","year":"2021","journal-title":"Am. J. Kidney Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1007\/s00467-021-04965-5","article-title":"Eculizumab exposure in children and young adults: Indications, practice patterns, and outcomes\u2014a Pediatric Nephrology Research Consortium study","volume":"36","author":"Sanderson","year":"2021","journal-title":"Pediatric Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.2215\/CJN.01360215","article-title":"Eculizumab in Pediatric Dense Deposit Disease","volume":"10","author":"Oosterveld","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1007\/s00467-018-4034-z","article-title":"Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in children and adolescents","volume":"33","author":"Holle","year":"2018","journal-title":"Pediatric Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1053\/j.ajkd.2017.11.019","article-title":"Patterns of Clinical Response to Eculizumab in Patients with C3 Glomerulopathy","volume":"72","author":"Lapeyraque","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/art.41901","article-title":"Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients with Granulomatosis with Polyangiitis or Microscopic Polyangiitis","volume":"74","author":"Brogan","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa041884","article-title":"Etanercept plus Standard Therapy for Wegener\u2019s Granulomatosis","volume":"352","author":"Null","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1136\/annrheumdis-2013-204164","article-title":"An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener\u2019s)","volume":"73","author":"Langford","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13075-022-02761-6","article-title":"Alemtuzumab for refractory primary systemic vasculitis\u2014A randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE)","volume":"24","author":"Gopaluni","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1136\/annrheumdis-2018-213032","article-title":"Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): Results from a randomised, double-blind, placebo-controlled trial","volume":"77","author":"Merrill","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e001747","DOI":"10.1136\/rmdopen-2021-001747","article-title":"Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: An across-study comparison","volume":"7","author":"Brunner","year":"2021","journal-title":"RMD Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1093\/rheumatology\/keab115","article-title":"Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus","volume":"60","author":"Wallace","year":"2021","journal-title":"Rheumatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"726667","DOI":"10.3389\/fphar.2021.726667","article-title":"Impact of Sampling Time Variability on Tacrolimus Dosage Regimen in Pediatric Primary Nephrotic Syndrome: Single-Center, Prospective, Observational Study","volume":"12","author":"Huang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/FTD.0000000000000871","article-title":"Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology","volume":"43","author":"Bergan","year":"2021","journal-title":"Ther. Drug Monit."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s40265-021-01618-7","article-title":"Clinical Value of Emerging Bioanalytical Methods for Drug Measurements: A Scoping Review of Their Applicability for Medication Adherence and Therapeutic Drug Monitoring","volume":"81","author":"Zijp","year":"2021","journal-title":"Drugs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"738788","DOI":"10.3389\/fimmu.2021.738788","article-title":"Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy","volume":"12","author":"Teisseyre","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00467-015-3082-x","article-title":"The glomerular permeability factors in idiopathic nephrotic syndrome","volume":"31","author":"Davin","year":"2015","journal-title":"Pediatric Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/s41390-018-0088-7","article-title":"Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome","volume":"84","author":"Bhatia","year":"2018","journal-title":"Pediatric Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s00467-013-2529-1","article-title":"Is rituximab effective in childhood nephrotic syndrome? Yes and no","volume":"29","author":"Kemper","year":"2013","journal-title":"Pediatric Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nm.1857","article-title":"The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A","volume":"14","author":"Faul","year":"2008","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"809456","DOI":"10.1155\/2012\/809456","article-title":"Is the Antiproteinuric Effect of Cyclosporine A Independent of Its Immunosuppressive Function in T Cells?","volume":"2012","author":"Zhang","year":"2012","journal-title":"Int. J. Nephrol."},{"key":"ref_49","first-page":"245","article-title":"Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid\u2013 Resistant Nephrotic Syndrome","volume":"11","author":"Beck","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00467-020-04695-0","article-title":"Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: A systematic review","volume":"36","author":"Malakasioti","year":"2021","journal-title":"Pediatric Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00467-010-1676-x","article-title":"Minimal change disease: A \u201ctwo-hit\u201d podocyte immune disorder?","volume":"26","author":"Shimada","year":"2011","journal-title":"Pediatric Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.semnephrol.2011.06.002","article-title":"Minimal Change Disease: A CD80 podocytopathy?","volume":"31","author":"Ishimoto","year":"2011","journal-title":"Semin. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1111\/ped.14005","article-title":"CD 80 expression and infiltrating regulatory T cells in idiopathic nephrotic syndrome of childhood","volume":"61","author":"Eroglu","year":"2019","journal-title":"Pediatric Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1007\/s00467-014-2874-8","article-title":"Minimal change disease: A dysregulation of the podocyte CD80\u2013 CTLA-4 axis?","volume":"29","author":"Wasserfall","year":"2014","journal-title":"Pediatric Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/ki.2010.143","article-title":"Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis","volume":"78","author":"Garin","year":"2010","journal-title":"Kidney Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00467-014-2915-3","article-title":"Urinary CD80 levels as a diagnostic biomarker of minimal change disease","volume":"30","author":"Ling","year":"2014","journal-title":"Pediatric Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa1304572","article-title":"Abatacept in B7-1\u2013 Positive Proteinuric Kidney Disease","volume":"369","author":"Yu","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"bcr2016214396","DOI":"10.1136\/bcr-2016-214396","article-title":"Abatacept experience in steroid and rituximab-resistant focal segmental glomeruloscle-rosis","volume":"2016","author":"Jayaraman","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6671552","DOI":"10.1155\/2021\/6671552","article-title":"CD80 Insights as Therapeutic Target in the Current and Future Treatment Options of Frequent-Relapse Minimal Change Disease","volume":"2021","author":"Teh","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nm.2261","article-title":"Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome","volume":"17","author":"Clement","year":"2010","journal-title":"Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cara-Fuentes, G., Segarra, A., Silva-Sanchez, C., Wang, H., Lanaspa, M.A., Johnson, R.J., and Garin, E.H. (2017). Angiopoietin-like-4 and minimal change disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176198"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1681\/ASN.2014030267","article-title":"Nephrotic Syndrome: Components, Connections, and Angiopoietin-Like 4\u2013Related Therapeutics","volume":"25","author":"Chugh","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.2215\/CJN.01710216","article-title":"All Things Complement","volume":"11","author":"Thurman","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fmed.2017.00099","article-title":"Complement in Non-Antibody-Mediated Kidney Diseases","volume":"4","author":"Angeletti","year":"2017","journal-title":"Front. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"599974","DOI":"10.3389\/fimmu.2020.599974","article-title":"Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys","volume":"11","author":"Koopman","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3389\/fped.2020.00205","article-title":"Clinical and Pathophysiological Insights into Immunological Mediated Glomerular Diseases in Childhood","volume":"8","author":"Mastrangelo","year":"2020","journal-title":"Front. Pediatric"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1007\/s00467-018-4076-2","article-title":"Biologics for childhood systemic vasculitis","volume":"34","author":"Akamine","year":"2018","journal-title":"Pediatric Nephrol."},{"key":"ref_68","first-page":"388","article-title":"Developing therapeutic \u2018arrows\u2019 with the precision of William Tell","volume":"24","author":"Mundel","year":"2015","journal-title":"Curr. Opin. Nephrol. Hypertens."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/4\/536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:51:31Z","timestamp":1760136691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/4\/536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,11]]},"references-count":68,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["children9040536"],"URL":"https:\/\/doi.org\/10.3390\/children9040536","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2022,4,11]]}}}