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Managing Lupus Nephritis in Children and Adolescents

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Abstract

Lupus nephritis is an important manifestation of systemic lupus erythematosus, which leads to chronic kidney disease, kidney failure, and can result in mortality. About 35%–60% of children with systemic lupus erythematosus develop kidney involvement. Over the past few decades, the outcome of patients with lupus nephritis has improved significantly with advances in immunosuppressive therapies and clinical management. Nonetheless, there is a paucity of high-level evidence to guide the management of childhood-onset lupus nephritis, because of the relatively small number of patients at each centre and also because children and adolescents are often excluded from clinical trials. Children and adults differ in more ways than just size, and there are remarkable differences between childhood- and adult-onset lupus nephritis in terms of disease severity, treatment efficacy, tolerance to medications and most importantly, psychosocial perspective. In this article, we review the ‘art and science’ of managing childhood-onset lupus nephritis, which has evolved in recent years, and highlight special considerations in this specific patient population.

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References

  1. Hersh AO, von Scheven E, Yazdany J, Panopalis P, Trupin L, Julian L, et al. Differences in long-term disease activity and treatment of adult patients with childhood-and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2009;61(1):13–20.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Fung KFK, Chan EY-h, Ma AL-t, Yeung W-l, Lai W-m, Kan EY-l. Vertical gaze palsy and intraoral numbness in a patient with neuro-psychiatric systemic lupus erythematosus: a case report and literature review. Lupus. 2020;29(13):1811–4.

  3. Chan EY-H, Leung KF, Soo ET, Ma AL. A Chinese boy with lupus anticoagulant-hypoprothrombinemia syndrome: a case report and review of the literature. J Pediatr Hematol Oncol. 2021;43(3):e445–e7.

  4. Yap DY, Tang CS, Ma MK, Lam MF, Chan TM. Survival analysis and causes of mortality in patients with lupus nephritis. Nephrol Dial Transplant. 2012;27(8):3248–54.

    Article  PubMed  Google Scholar 

  5. Chan EYH, Yap DYH, Wong WHS, Ho TW, Tong PC, Lai WM, et al. Demographics and long-term outcomes of children with end-stage kidney disease: a 20-year territory-wide study. Nephrology (Carlton). 2022;27(2):171–80.

    Article  CAS  PubMed  Google Scholar 

  6. Oni L, Wright RD, Marks S, Beresford MW, Tullus K. Kidney outcomes for children with lupus nephritis. Pediatr Nephrol. 2021;36(6):1377–85.

    Article  PubMed  Google Scholar 

  7. Wenderfer SE, Chang JC, Davies AG, Luna IY, Scobell R, Sears C, et al. Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes. Clin J Am Soc Nephrol. 2022;17(1):65–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Weening JJ, D’agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65(2):521–30.

    Article  PubMed  Google Scholar 

  9. Markowitz G, D’agati V. The ISN/RPS 2003 classification of lupus nephritis: an assessment at 3 years. Kidney Int. 2007;71(6):491–5.

    Article  CAS  PubMed  Google Scholar 

  10. Chan EY-h, Yap DY-h, Wong W-t, Wong WH-s, Wong S-w, Lin KY-k, et al. Long-term outcomes of children and adolescents with biopsy-proven childhood-onset lupus nephritis. Kidney Int Rep. 2023;8(1):141–50.

  11. Kwon Y-C, Chun S, Kim K, Mak A. Update on the genetics of systemic lupus erythematosus: genome-wide association studies and beyond. Cells. 2019;8(10):1180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pineles D, Valente A, Warren B, Peterson M, Lehman T, Moorthy L. Worldwide incidence and prevalence of pediatric onset systemic lupus erythematosus. Lupus. 2011;20(11):1187–92.

    Article  CAS  PubMed  Google Scholar 

  13. Watson L, Beresford M, Maynes C, Pilkington C, Marks S, Glackin Y, et al. The indications, efficacy and adverse events of rituximab in a large cohort of patients with juvenile-onset SLE. Lupus. 2015;24(1):10–7.

    Article  CAS  PubMed  Google Scholar 

  14. Kanda N, Tsuchida T, Tamaki K. Estrogen enhancement of anti–double-stranded DNA antibody and immunoglobulin G production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum. 1999;42(2):328–37.

    Article  CAS  PubMed  Google Scholar 

  15. Patel M, Clarke AM, Bruce IN, Symmons DP. The prevalence and incidence of biopsy-proven lupus nephritis in the UK: evidence of an ethnic gradient. Arthritis Rheum. 2006;54(9):2963–9.

    Article  PubMed  Google Scholar 

  16. De Mutiis C, Wenderfer SE, Orjuela A, Bagga A, Basu B, Sar T, et al. Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis. Rheumatology (Oxford). 2021.

  17. Groot N, Shaikhani D, Teng Y, de Leeuw K, Bijl M, Dolhain R, et al. Long-term clinical outcomes in a cohort of adults with childhood-onset systemic lupus erythematosus. Arthritis Rheum. 2019;71(2):290–301.

    Article  CAS  Google Scholar 

  18. Demir S, Gülhan B, Özen S, Çeleğen K, Batu ED, Taş N, et al. Long-term renal survival of paediatric patients with lupus nephritis. Nephrol Dial Transplant. 2021.

  19. Qiu S, Zhang H, Yu S, Yang Q, Zhang G, Yang H, et al. Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis. Pediatr Nephrol. 2022;37(2):367–76.

    Article  PubMed  Google Scholar 

  20. Wong S-N, Tse K-C, Lee T-L, Lee K-W, Chim S, Lee K-P, et al. Lupus nephritis in Chinese children–a territory-wide cohort study in Hong Kong. Pediatr Nephrol. 2006;21(8):1104–12.

    Article  PubMed  Google Scholar 

  21. Vachvanichsanong P, Dissaneewate P, McNeil E. Diffuse proliferative glomerulonephritis does not determine the worst outcome in childhood-onset lupus nephritis: a 23-year experience in a single centre. Nephrol Dial Transplant. 2009;24(9):2729–34.

    Article  PubMed  Google Scholar 

  22. Hari P, Bagga A, Mahajan P, Dinda A. Outcome of lupus nephritis in Indian children. Lupus. 2009;18(4):348–54.

    Article  CAS  PubMed  Google Scholar 

  23. Pereira T, Abitbol CL, Seeherunvong W, Katsoufis C, Chandar J, Freundlich M, et al. Three decades of progress in treating childhood-onset lupus nephritis. Clin J Am Soc Nephrol. 2011;6(9):2192–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Taheri S, Beiraghdar F. Lupus nephritis in Iranian children: a review of 60 patients. Ren Fail. 2011;33(5):499–505.

    Article  PubMed  Google Scholar 

  25. Srivastava P, Abujam B, Misra R, Lawrence A, Agarwal V, Aggarwal A. Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years. Lupus. 2016;25(5):547–57.

    Article  CAS  PubMed  Google Scholar 

  26. Suhlrie A, Hennies I, Gellermann J, Büscher A, Hoyer P, Waldegger S, et al. Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study. Pediatr Nephrol. 2020;35(7):1235–46.

    Article  PubMed  Google Scholar 

  27. Chan EY-h, Liu M-s, Or P-c, Ma AL-t. Outcomes and perception of cloud-based remote patient monitoring in children receiving automated peritoneal dialysis: a prospective study. Pediatr Nephrol. 2023;38(7):2171–2178.

  28. Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, et al. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4):S1–276.

    Article  Google Scholar 

  29. Furie R, Nicholls K, Cheng TT, Houssiau F, Burgos-Vargas R, Chen SL, et al. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheum. 2014;66(2):379–89.

    Article  CAS  Google Scholar 

  30. Liang M, Schur P, Fortin P. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria. The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Arthritis Rheum. 2006;54(2):421–32.

  31. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215–26.

    Article  CAS  PubMed  Google Scholar 

  32. Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Group AT. Treatment of lupus nephritis with abatacept: the abatacept and cyclophosphamide combination efficacy and safety study. Arthritis Rheum. 2014;66(11):3096–104.

    Article  Google Scholar 

  34. Furie R, Rovin BH, Houssiau F, Malvar A, Teng YO, Contreras G, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020;383(12):1117–28.

    Article  CAS  PubMed  Google Scholar 

  35. Aragon E, Resontoc L, Chan Y, Lau Y, Tan P, Loh H, et al. Long-term outcomes with multi-targeted immunosuppressive protocol in children with severe proliferative lupus nephritis. Lupus. 2016;25(4):399–406.

    Article  CAS  PubMed  Google Scholar 

  36. Tselios K, Gladman DD, Urowitz MB. How can we define low disease activity in systemic lupus erythematosus? Sem Arthritis Rheum; 2019: Elsevier. p. 1035–40.

  37. Kisaoglu H, Baba O, Kalyoncu M. Lupus low disease activity state as a treatment target for pediatric patients with lupus nephritis. Pediatr Nephrol. 2023;38(4):1167–75.

    Article  PubMed  Google Scholar 

  38. Wahadat MJ, Van Den Berg L, Timmermans D, Van Rijswijk K, van Dijk-Hummelman A, Bakx S, et al. LLDAS is an attainable treat-to-target goal in childhood-onset SLE. Lupus Sci Med. 2021;8(1): e000571.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lopes SR, Gormezano N, Gomes RC, Aikawa NE, Pereira RM, Terreri MT, et al. Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups. Lupus. 2017;26(9):996–1001.

    Article  CAS  PubMed  Google Scholar 

  40. Gibson KL, Gipson DS, Massengill SA, Dooley MA, Primack WA, Ferris MA, et al. Predictors of relapse and end stage kidney disease in proliferative lupus nephritis: focus on children, adolescents, and young adults. Clin J Am Soc Nephrol. 2009;4(12):1962–7.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wenderfer SE, Orjuela A, Bekheirnia MR, Pereira M, Muscal E, Braun MC, et al. Lupus nephritis, autoantibody production and kidney outcomes in males with childhood-onset systemic lupus erythematosus. Pediatric Rep. 2022;14(2):220–32.

    Article  Google Scholar 

  42. Ruggiero B, Vivarelli M, Gianviti A, Benetti E, Peruzzi L, Barbano G, et al. Lupus nephritis in children and adolescents: results of the Italian Collaborative Study. Nephrol Dial Transplant. 2013;28(6):1487–96.

    Article  CAS  PubMed  Google Scholar 

  43. Lee BS, Cho HY, Kim EJ, Kang HG, Ha IS, Cheong HI, et al. Clinical outcomes of childhood lupus nephritis: a single center’s experience. Pediatr Nephrol. 2007;22(2):222–31.

    Article  PubMed  Google Scholar 

  44. Chan EY-h, Yap DY-h, Wong WH-s, Wong S-w, Lin KY-k, Hui FY-w, et al. Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study. rheumatology (Oxford). 2023 Aug 26:kead447. https://doi.org/10.1093/rheumatology/kead447(Online ahead of print).

  45. Groot N, De Graeff N, Marks SD, Brogan P, Avcin T, Bader-Meunier B, et al. European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative. Ann Rheum Dis. 2017;76(12):1965–73.

    Article  CAS  PubMed  Google Scholar 

  46. Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hié M, de Chambrun MP, et al. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020;79(3):339–46.

    Article  CAS  PubMed  Google Scholar 

  47. Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013;72(8):1280–6.

    Article  CAS  PubMed  Google Scholar 

  48. Yap DY, Chan TM. What is the ideal duration of maintenance therapy for lupus nephritis? Expert Rev Clin Immunol. 2022;18(5):425–7.

    Article  CAS  PubMed  Google Scholar 

  49. LeBlanc W, Gladman D, Urowitz M. Serologically active clinically quiescent systemic lupus erythematosus–predictors of clinical flares. J Rheumatol. 1994;21(12):2239–41.

    Google Scholar 

  50. Yap DY, Kwan LP, Ma MK, Mok MM, Chan GC, Chan TM. Preemptive immunosuppressive treatment for asymptomatic serological reactivation may reduce renal flares in patients with lupus nephritis: a cohort study. Nephrol Dial Transplant. 2019;34(3):467–73.

    Article  CAS  PubMed  Google Scholar 

  51. Sit JK, Chan WK. Risk factors for damage in childhood-onset systemic lupus erythematosus in Asians: a case control study. Pediatr Rheumatol. 2018;16(1):1–11.

    Article  Google Scholar 

  52. Lilleby V, Lien G, Frey Frøslie K, Haugen M, Flatø B, Førre Ø. Frequency of osteopenia in children and young adults with childhood-onset systemic lupus erythematosus. Arthritis Rheum. 2005;52(7):2051–9.

    Article  PubMed  Google Scholar 

  53. Takada K, Illei G, Boumpas D. Cyclophosphamide for the treatment of systemic lupus erythematosus. Lupus. 2001;10(3):154–61.

    Article  CAS  PubMed  Google Scholar 

  54. Chan EY, Warady BA. Acquired cystic kidney disease: an under-recognized condition in children with end-stage renal disease. Pediatr Nephrol. 2018;33(1):41–51.

    Article  PubMed  Google Scholar 

  55. Chan EY, Warady BA. Acquired cystic kidney disease. Pediatric dialysis case studies. Springer; 2017. p. 335–41.

  56. Singh JA, Shah NP, Mudano AS. Belimumab for systemic lupus erythematosus. Cochrane Database Syst Rev. 2021(2).

  57. Costedoat-Chalumeau N, Houssiau FA. Improving medication adherence in patients with lupus nephritis. Kidney Int. 2021;99(2):285–7.

    Article  PubMed  Google Scholar 

  58. Costedoat-Chalumeau N, Tamirou F, Piette J-C. Treatment adherence in systemic lupus erythematosus and rheumatoid arthritis: time to focus on this important issue. Rheumatology (Oxford). 2018. p. 1507–9.

  59. Cunha C, Alexander S, Ashby D, Lee J, Chusney G, Cairns TD, et al. Hydroxycloroquine blood concentration in lupus nephritis: a determinant of disease outcome? Nephrol Dial Transplant. 2018;33(9):1604–10.

    CAS  PubMed  Google Scholar 

  60. Costedoat-Chalumeau N, Pouchot J, Guettrot-Imbert G, Le Guern V, Leroux G, Marra D, et al. Adherence to treatment in systemic lupus erythematosus patients. Best Pract Res Clin Rheumatol. 2013;27(3):329–40.

    Article  PubMed  Google Scholar 

  61. Feldman CH, Yazdany J, Guan H, Solomon DH, Costenbader KH. Medication nonadherence is associated with increased subsequent acute care utilization among medicaid beneficiaries with systemic lupus erythematosus. Arthritis Rheum. 2015;67(12):1712–21.

    Article  CAS  Google Scholar 

  62. Felsenstein S, Reiff AO, Ramanathan A. Transition of care and health-related outcomes in pediatric-onset systemic lupus erythematosus. Arthritis Rheum. 2015;67(11):1521–8.

    Article  Google Scholar 

  63. Deapen DEA. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992;1992:311–8.

    Google Scholar 

  64. Hiraki LT, Silverman ED. Genomics of systemic lupus erythematosus: insights gained by studying monogenic young-onset systemic lupus erythematosus. Rheum Dis Clin N Am. 2017;43(3):415–34.

    Article  Google Scholar 

  65. Alperin JM, Ortiz-Fernández L, Sawalha AH. Monogenic lupus: a developing paradigm of disease. Front immunol. 2018;9:2496.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34(3):J276–86.

    Article  CAS  PubMed  Google Scholar 

  67. Agrebi N, Ben-Mustapha I, Matoussi N, Dhouib N, Ben-Ali M, Mekki N, et al. Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome. Clin Immunol. 2017;183:17–23.

    Article  CAS  PubMed  Google Scholar 

  68. Wenderfer SE, Lane JC, Shatat IF, Von Scheven E, Ruth NM. Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest Pediatr Nephrol Consortium and the Childhood Arthritis and Rheumatology Research Alliance. Pediatr Rheumatol Online J. 2015;13:1–8.

    Article  Google Scholar 

  69. Parodis I, Tamirou F, Houssiau FA. Treat-to-target in lupus nephritis. what is the role of the repeat kidney biopsy? Arch Immunol Ther Exp (Warsz). 2022;70(1):8.

  70. Li X, Ren H, Zhang Q, Zhang W, Wu X, Xu Y, et al. Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant. 2012;27(4):1467–72.

    Article  CAS  PubMed  Google Scholar 

  71. Rathi M, Goyal A, Jaryal A, Sharma A, Gupta PK, Ramachandran R, et al. Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int. 2016;89(1):235–42.

    Article  CAS  PubMed  Google Scholar 

  72. Chbihi M, Eveillard L-A, Riller Q, Brousse R, Berthaud R, Quartier P, et al. Induction therapy for pediatric onset class IV lupus nephritis: mycophenolate mofetil versus cyclophosphamide. J Nephrol. 2023;36(3):829–39.

    Article  CAS  PubMed  Google Scholar 

  73. Smitherman EA, Chahine RA, Beukelman T, Lewandowski LB, Rahman AF, Wenderfer SE, et al. Childhood-onset lupus nephritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: short-term kidney status and variation in care. Arthritis Rheum. 2023;75(7):1553–62.

    Article  Google Scholar 

  74. Chan E, Ma L, Mak Y, Lai W. POS-135 renal vascular lesions in childhood-onset lupus nephritis: a tertiary centre experience. Kidney Int Rep. 2021;6(4):S54–5.

    Article  Google Scholar 

  75. Gheet FS, Dawoud HE-S, El-Shahaby WA, Elrifaey SM, Abdelnabi HH. Hydroxychloroquine in children with proliferative lupus nephritis: a randomized clinical trial. Eur J Pediatr. 2023:1–11.

  76. Rovin BH, Teng YO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;397(10289):2070–80.

    Article  CAS  PubMed  Google Scholar 

  77. Saadeh SA, Baracco R, Jain A, Kapur G, Mattoo TK, Valentini RP. Weight or body surface area dosing of steroids in nephrotic syndrome: is there an outcome difference? Pediatr Nephrol. 2011;26:2167–71.

    Article  PubMed  Google Scholar 

  78. Mina R, Von Scheven E, Ardoin SP, Eberhard BA, Punaro M, Ilowite N, et al. Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus. Arthritis Rheum. 2012;64(3):375–83.

    Article  Google Scholar 

  79. Cooper JC, Rouster-Stevens K, Wright TB, Hsu JJ, Klein-Gitelman MS, Ardoin SP, et al. Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis. Pediatr Rheumatol Online J. 2018;16(1):1–11.

    Article  Google Scholar 

  80. Chalhoub NE, Wenderfer SE, Levy DM, Rouster-Stevens K, Aggarwal A, Savani SI, et al. International consensus for the dosing of corticosteroids in childhood-onset systemic lupus erythematosus with proliferative lupus nephritis. Arthritis Rheum. 2022;74(2):263–73.

    Article  CAS  Google Scholar 

  81. Chan EY-h, Ellen L, Angeletti A, Arslan Z, Basu B, Boyer O, et al. Long-term efficacy and safety of repeated rituximab to maintain remission in idiopathic childhood nephrotic syndrome: an international study. J Am Soc Nephrol. 2022;33(6):1193–207.

  82. Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae S-C, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2023.

  83. Bergan S, Brunet M, Hesselink DA, Johnson-Davis KL, Kunicki PK, Lemaitre F, et al. Personalized therapy for mycophenolate: consensus report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 2021;43(2):150–200.

    Article  CAS  PubMed  Google Scholar 

  84. Yap DY, Tam CH, Yung S, Wong S, Tang CS, Mok TM, et al. Pharmacokinetics and pharmacogenomics of mycophenolic acid and its clinical correlations in maintenance immunosuppression for lupus nephritis. Nephrol Dial Transplant. 2020;35(5):810–8.

    Article  CAS  PubMed  Google Scholar 

  85. Kim JS, Aviles DH, Silverstein DM, LeBlanc PL, Matti VV. Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients. Pediatr transplant. 2005;9(2):162–9.

    Article  CAS  PubMed  Google Scholar 

  86. Cooney GF, Habucky K, Hoppu K. Cyclosporin pharmacokinetics in paediatric transplant recipients. Clin pharmacokinet. 1997;32(6):481–95.

    Article  CAS  PubMed  Google Scholar 

  87. Lai FF-y, Chan EY-h, Tullus K, Ma AL-t. Therapeutic drug monitoring in childhood idiopathic nephrotic syndrome: a state of the art review. Pediatr Nephrol. 2023:1–19.

  88. Nishimura T, Uemura O, Hibino S, Tanaka K, Kitagata R, Yuzawa S, et al. Serum albumin level is associated with mycophenolic acid concentration in children with idiopathic nephrotic syndrome. Eur J Pediatr. 2022;181(3):1159–65.

    Article  CAS  PubMed  Google Scholar 

  89. de Winter BC, van Gelder T, Sombogaard F, Shaw LM, van Hest RM, Mathot RA. Pharmacokinetic role of protein binding of mycophenolic acid and its glucuronide metabolite in renal transplant recipients. J Pharmacokinet Pharmacodyn. 2009;36:541–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin pharmacokinet. 2007;46:13–58.

    Article  CAS  PubMed  Google Scholar 

  91. Fujinaga S, Nishino T. Ten-year treatment with mycophenolate mofetil using therapeutic drug monitoring for childhood-onset lupus nephritis in Japan. Pediatr Nephrol. 2017;32:189–90.

    Article  PubMed  Google Scholar 

  92. Gellermann J, Weber L, Pape L, Tönshoff B, Hoyer P, Querfeld U. Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol. 2013;24(10):1689–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Godron-Dubrasquet A, Decramer S, Fila M, Guigonis V, Tellier S, Scaon M, et al. Mycophenolic acid area under the curve is associated with therapeutic response in pediatric lupus nephritis. Pediatr Nephrol. 2021;36(2):341–7.

    Article  PubMed  Google Scholar 

  94. Beaulieu Q, Zhang D, Melki I, Baudouin V, Goldwirst L, Woillard J-B, et al. Pharmacokinetics of mycophenolic acid and external evaluation of two limited sampling strategies of drug exposure in patients with juvenile systematic lupus erythematosus. Eur J Clin Pharmacol. 2022;78(6):1003–10.

    Article  CAS  PubMed  Google Scholar 

  95. Cannon LA, Wenderfer SE, Lewandowski LB, Cooper JC, Goilav B, Knight AM, et al. Use of EuroLupus cyclophosphamide dosing for the treatment of lupus nephritis in childhood-onset systemic lupus erythematosus in North America. J Rheumatol. 2022;49(6):607–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Faurschou M, Sorensen IJ, Mellemkjaer L, Loft AGR, Thomsen BS, Tvede N, et al. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol. 2008;35(1):100–5.

    CAS  PubMed  Google Scholar 

  97. Green DM, Liu W, Kutteh WH, Ke RW, Shelton KC, Sklar CA, et al. Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol. 2014;15(11):1215–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Tamirou F, Husson SN, Gruson D, Debieve F, Lauwerys BR, Houssiau FA. The euro-lupus low-dose intravenous cyclophosphamide regimen does not impact the ovarian reserve, as measured by serum levels of anti-Müllerian hormone. Arthritis Rheumatol. 2017;69(6):1267–71.

    Article  CAS  PubMed  Google Scholar 

  99. Chemaitilly W, Li Z, Krasin MJ, Brooke RJ, Wilson CL, Green DM, et al. Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab. 2017;102(7):2242–50.

  100. Chan EY-h, Tullus K. Rituximab in children with steroid sensitive nephrotic syndrome: in quest of the optimal regimen. Pediatr Nephrol. 2021;36(6):1397–1405. https://doi.org/10.1007/s00467-020-04609-0.

  101. Marlais M, Wlodkowski T, Printza N, Kronsteiner D, Krisam R, Sauer L, et al. Clinical factors and adverse kidney outcomes in children with ANCA-associated glomerulonephritis. Am J Kidney Dis. 2023;81(1):119–22. https://doi.org/10.1053/j.ajkd.2022.05.013.

    Article  PubMed  Google Scholar 

  102. Chan EY-h, Webb H, Yu E, Ghiggeri GM, Kemper MJ, Ma AL-t, et al. Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes. Kidney Int. 2020;97(2):393–401.

  103. Chan E, Yap D, Colucci M, Ma AL-t, Parekh R, Tullus K. Use of rituximab in childhood idiopathic nephrotic syndrome. Clin J Am Soc Nephrol. 18(4):533–548. https://doi.org/10.2215/CJN.08570722.

  104. Chan EY-h, Ma AL-t, Tullus K. Hypogammaglobulinaemia following rituximab therapy in childhood nephrotic syndrome. Pediatr Nephrol. 2022;37(5):927–31.

  105. Basu B, Roy B, Babu BG. Efficacy and safety of rituximab in comparison with common induction therapies in pediatric active lupus nephritis. Pediatr Nephrol. 2017;32:1013–21.

    Article  PubMed  Google Scholar 

  106. Hogan J, Godron A, Baudouin V, Kwon T, Harambat J, Deschênes G, et al. Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis. Pediatr Nephrol. 2018;33(1):111–6.

    Article  PubMed  Google Scholar 

  107. Nwobi O, Abitbol CL, Chandar J, Seeherunvong W, Zilleruelo G. Rituximab therapy for juvenile-onset systemic lupus erythematosus. Pediatr Nephrol. 2008;23(3):413–9.

    Article  PubMed  Google Scholar 

  108. Chan EY-h, Wong S-w, Lai FF-y, Ho T-w, Tong P-c, Lai W-m, et al. Long-term outcomes with rituximab as add-on therapy in severe childhood-onset lupus nephritis. Pediatr Nephrol. 2023;38(12):4001–4011. https://doi.org/10.1007/s00467-023-06025-6.

  109. Malakasioti G, Iancu D, Milovanova A, Tsygin A, Horinouchi T, Nozu K, et al. A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants. Kidney Int. 2023;103(5):962–72.

    Article  CAS  PubMed  Google Scholar 

  110. Yap DY, Li PH, Tang C, So BY, Kwan LP, Chan GC, et al. Long-term results of triple immunosuppression with tacrolimus added to mycophenolate and corticosteroids in the treatment of lupus nephritis. Kidney Int rep. 2022;7(3):516–25.

    Article  PubMed  Google Scholar 

  111. Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med. 2015;162(1):18–26.

    Article  PubMed  Google Scholar 

  112. Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(1):100–7.

    Article  CAS  PubMed  Google Scholar 

  113. Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021.

  114. Yap DYH, Mok CC. Novel and emerging treatment strategies for lupus nephritis. Expert Rev Clin Pharmacol. 2022;15(11):1283–92.

    Article  CAS  PubMed  Google Scholar 

  115. Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31.

    Article  CAS  PubMed  Google Scholar 

  116. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Brunner HI, Abud-Mendoza C, Viola DO, Penades IC, Levy D, Anton J, et al. Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis. 2020;79(10):1340–8.

    Article  CAS  PubMed  Google Scholar 

  118. Anders HJ, Furie R, Malvar A, Zhao MH, Hiromura K, Weinmann-Menke J, Green Y, Jones-Leone A, Negrini D, Levy RA, Lightstone L, Tanaka Y, Rovin BH. Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial. Nephrol Dial Transplant. 2023:gfad167. https://doi.org/10.1093/ndt/gfad167.

  119. Rovin BH, Solomons N, Pendergraft WF III, Dooley MA, Tumlin J, Romero-Diaz J, et al. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int. 2019;95(1):219–31.

    Article  CAS  PubMed  Google Scholar 

  120. Vilet JMM, Liu Z-H, Chan TM. Choosing the right treatment in patients with lupus nephritis. Clin J Am Soc Nephrol. 2022;17(9):1399–402.

    Article  Google Scholar 

  121. Chan EY-h, Ma AL-t, Tullus K. When should we start and stop ACEi/ARB in paediatric chronic kidney disease? Pediatr Nephrol. 2021;36(7):1751–64.

  122. Sakamoto AP, Silva CA, Islabão AG, Novak GV, Molinari B, Nogueira PK, et al. Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus. Pediatr Nephrol. 2023;38(6):1843–54.

    Article  PubMed  Google Scholar 

  123. Prabha R, Mathew B, Jeyaseelan V, Kumar T, Agarwal I, Fleming D. Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus. Indian J Nephrol. 2016;26(6):408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Mizaki T, Nobata H, Banno S, Yamaguchi M, Kinashi H, Iwagaitsu S, et al. Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis. J Pharm Health Care Sci. 2023;9(1):1–13.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Paediatric Nephrology Centre, Hong Kong Children’s Hospital, Kowloon, Hong Kong

    Eugene Yu-hin Chan, Fiona Fung-yee Lai, Alison Lap-tak Ma & Tak Mao Chan

  2. Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, School of Clinical Medicine, Pok Fu Lam, Hong Kong

    Tak Mao Chan

  3. Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Eugene Yu-hin Chan & Alison Lap-tak Ma

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Chan, E.Yh., Lai, F.Fy., Ma, A.Lt. et al. Managing Lupus Nephritis in Children and Adolescents. Pediatr Drugs 26, 145–161 (2024). https://doi.org/10.1007/s40272-023-00609-3

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