Journal of Clinical Pediatrics >
Re-recognition of the complement involvement in the pathogenesis of kidney diseases in children
Received date: 2023-07-03
Online published: 2024-05-10
Complement is an important component of innate immunity, as well as a bridge to regulate adaptive immunity. It is an important substance that mediates cellular inflammatory response and induces apoptosis. The cascade of the complement response is stictly regulated by the stringent control of the complennent regulatory proteins. Should the complement overactivated or regulate abnormally, it can cause damage to the host cells. In the glomerular microenvironment, dysregulation of the complement system can lead to C3 glomerulopathy and atypical hemolytic uremic syndrome. In addition, complement is also hyperactivated in many other inflammatory kidney diseases, such as ANCA-associated glomerulonephritis, lupus nephritis, IgA nephropathy, membranous nephropathy, and diabetic nephropathy. In addition, it may mediate renal allograft injury by playing a role in ischemia-reperfusion injury and rejection. This article reviews the role of complement in the pathogenesis of glomerular diseases and related targeted therapy.
Key words： complement; kidney disease; targeted Therapy
Peipei Reviewer: WANG , Pei ZHANG , Chunlin Reviser: GAO , Zhengkun XIA . Re-recognition of the complement involvement in the pathogenesis of kidney diseases in children[J]. Journal of Clinical Pediatrics, 2024 , 42(5) : 467 -473 . DOI: 10.12372/jcp.2024.23e0595
| [1] | Borza DB. Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation[J]. Matrix Biol, 2017(57-58): 299-310. |
| [2] | Gavriilaki E, Anagnostopoulos A, Mastellos DC. Complement in thrombotic microangiopathies: unraveling ariadne's thread into the labyrinth of complement therapeutics[J]. Front Immunol, 2019, 10: 337. |
| [3] | Leon J, LeStang MB, Sberro-Soussan R, et al. Complement-driven hemolytic uremic syndrome[J]. Am J Hematol, 2023, 98(Suppl 4): S44-S56. |
| [4] | Blasco M, Guillén-Olmos E, Diaz-Ricart M, et al. Complement mediated endothelial damage in thrombotic microangiopathies[J]. Front Med (Lausanne), 2022, 9: 811504. |
| [5] | ?z?akar ZB, Ozaltin F, Gülhan B, et al. Transplantation in pediatric aHUS within the era of eculizumab therapy[J]. Pediatr Transplant, 2021, 25(3): e13914. |
| [6] | Tang ZC, Hui H, Shi C, et al. New findings in preventing recurrence and improving renal function in AHUS patients after renal transplantation treated with eculizumab: a systemic review and meta-analyses[J]. Ren Fail, 2023, 45(1): 2231264. |
| [7] | Fakhouri F, Fila M, Hummel A, et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study[J]. Blood, 2021, 137(18): 2438-2449. |
| [8] | Palma LMP, Eick RG, Dantas GC, et al. Atypical hemolytic uremic syndrome in Brazil: clinical presentation, genetic findings and outcomes of a case series in adults and children treated with eculizumab[J]. Clin Kidney J, 2021, 14(4): 1126-1135. |
| [9] | Jodele S, Dandoy CE, Lane A, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab[J]. Blood, 2020, 135(13): 1049-1057. |
| [10] | Heiderscheit AK, Hauer JJ, Smith RJH. C3 glomerulopathy: Understanding an ultra-rare complement-mediated renal disease[J]. Am J Med Genet C Semin Med Genet, 2022, 190(3): 344-357. |
| [11] | Kant S, Kronbichler A, Sharma P, et al. Advances in understanding of pathogenesis and treatment of immune-mediated kidney disease: a review[J]. Am J Kidney Dis, 2022, 79(4): 582-600. |
| [12] | Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis-a new look at an old entity[J]. N Engl J Med, 2012, 366(12): 1119-1131. |
| [13] | Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the management of glomerular diseases[J]. Kidney Int, 2021, 100(4): 753-779. |
| [14] | Michels M, Wijnsma KL, Kurvers RAJ, et al. Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort[J]. Pediatr Nephrol, 2022, 37(3): 601-612. |
| [15] | Günay N, Dursun ?, G?k?e ?, et al. Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?[J]. Pediatr Nephrol, 2024, 39(5): 1435-1446. |
| [16] | Caravaca-Fontán F, Lucientes L, Cavero T, et al. Update on C3 glomerulopathy: a complement-mediated disease[J]. Nephron, 2020, 144(6): 272-280. |
| [17] | Chauvet S, Hauer JJ, Petitprez F, et al. Results from a nationwide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy[J]. Kidney Int, 2022, 102(4): 904-916. |
| [18] | Pinarbasi AS, Dursun I, Poyrazoglu MH, et al. Evaluation of the children with C3 glomerulopathy[J]. Saudi J Kidney Dis Transpl, 2020, 31(1): 79-89. |
| [19] | Zotta F, Diomedi-Camassei F, Gargiulo A, et al. Successful treatment with avacopan (CCX168) in a pediatric patient with C3 glomerulonephritis[J]. Pediatr Nephrol, 2023, 38(12): 4197-4201. |
| [20] | Goodship TH, Cook HT, Fakhouri F, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference[J]. Kidney Int, 2017, 91(3): 539-551. |
| [21] | Mazzariol M, Manenti L, Vaglio A. The complement system in antineutrophil cytoplasmic antibody-associated vasculitis: pathogenic player and therapeutic target[J]. Curr Opin Rheumatol, 2023, 35(1): 31-36. |
| [22] | Moiseev S, Lee JM, Zykova A, et al. The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis[J]. Clin Exp Immunol, 2020, 202(3): 394-402. |
| [23] | Zhang P, Yan SJ, Hu J, et al. EXPRESS: Clinical outcomes and clinico-pathological correlations in children with MPO-ANCA-associated glomerulonephritis showing renal arteritis[J]. J Investig Med, 2024: 10815589241248073. |
| [24] | Johansson L, Berglin E, Eriksson O, et al. Complement activation prior to symptom onset in myeloperoxidase ANCA-associated vasculitis but not proteinase 3 ANCA associated vasculitis - A Swedish biobank study[J]. Scand J Rheumatol, 2022, 51(3): 214-219. |
| [25] | García L, Pena CE, Maldonado R, et al. Increased renal damage in hypocomplementemic patients with ANCA-associated vasculitis: retrospective cohort study[J]. Clin Rheumatol, 2019, 38(10): 2819-2824. |
| [26] | Antovic A, Mobarrez F, Manojlovic M, et al. Microparticles expressing myeloperoxidase and complement C3a and C5a as markers of renal involvement in antineutrophil cytoplasmic antibody-associated vasculitis[J]. J Rheumatol, 2020, 47(5): 714-721. |
| [27] | Turgeon D, Bakowsky V, Baldwin C, et al. CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum[J]. Rheumatology (Oxford), 2023, 62(8): 2646-2651. |
| [28] | Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis[J]. N Engl J Med, 2021, 384(7): 599-609. |
| [29] | Zhang P, Yang X, Fang X, et al. Anti-C1q antibodies in lupus nephritis children with glomerular microthrombosis[J]. Nephrology (Carlton), 2023, 28(9): 485-494. |
| [30] | Ye B, Chen B, Guo C, et al. C5a-C5aR1 axis controls mitochondrial fission to promote podocyte injury in lupus nephritis[J]. Mol Ther, 2024: S1525-0016(24)00144-8. |
| [31] | Chen K, Deng Y, Shang S, et al. Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice[J]. Biomed Pharmacother, 2022, 153: 113433. |
| [32] | Wright RD, Bannerman F, Beresford MW, et al. A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic micro-angiopathy[J]. BMC Nephrol, 2020, 21(1): 245. |
| [33] | Al Hussain T, Hussein MH, Al Mana H, et al. Patho-physiology of IgA nephropathy[J]. Adv Anat Pathol, 2017, 24(1): 56-62. |
| [34] | Barratt J, Lafayette RA, Zhang H, et al. IgA nephropathy: the lectin pathway and implications for targeted therapy[J]. Kidney Int, 2023, 104(2): 254-264. |
| [35] | Mizerska-Wasiak M, Such-Gruchot A, Cichoń-Kawa K, et al. The role of complement component C3 activation in the clinical presentation and prognosis of IgA nephropathy-A National Study in Children[J]. J Clin Med, 2021, 10(19):4405. |
| [36] | Kistler AD, Salant DJ. Complement activation and effector pathways in membranous nephropathy[J]. Kidney Int, 2024, 105(3): 473-483. |
| [37] | Gao S, Cui Z, Zhao MH. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy[J]. J Am Soc Nephrol, 2022, 33(9): 1742-1756. |
| [38] | Haddad G, Lorenzen JM, Ma H, et al. Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1-associated membranous nephropathy[J]. J Clin Invest, 2021, 131(5):e140453. |
| [39] | Seifert L, Zahner G, Meyer-Schwesinger C, et al. The classical pathway triggers pathogenic complement activation in membranous nephropathy[J]. Nat Commun, 2023, 14(1): 473. |
| [40] | Zhang Q, Bin S, Budge K, et al. C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy[J]. JCI Insight, 2024, 9(4): e172976. |
| [41] | Zheng JM, Ren XG, Jiang ZH, et al. Lectin-induced renal local complement activation is involved in tubular interstitial injury in diabetic nephropathy[J]. Clin Chim Acta, 2018, 482: 65-73. |
| [42] | Flyvbjerg A. The role of the complement system in diabetic nephropathy[J]. Nat Rev Nephrol, 2017, 13(5): 311-318. |
| [43] | Pesce F, Stea ED, Rossini M, et al. Glomerulonephritis in AKI: from pathogenesis to therapeutic intervention[J]. Front Med (Lausanne), 2020, 7: 582272. |
| [44] | Huang J, Cui Z, Gu QH, et al. Complement activation profile of patients with primary focal segmental glomerulosclerosis[J]. PLoS One, 2020, 15(6): e0234934. |
| [45] | Wang C, Wang Z, Zhang W. The potential role of complement alternative pathway activation in hypertensive renal damage[J]. Exp Biol Med (Maywood), 2022, 247(9): 797-804. |
| [46] | Nithagon P, Cortazar F, Shah SI, et al. Eculizumab and complement activation in anti-glomerular basement membrane disease[J]. Kidney Int Rep, 2021, 6(10): 2713-2717. |
| [47] | Golshayan D, Schwotzer N, Fakhouri F, et al. Targeting the complement pathway in kidney transplantation[J]. J Am Soc Nephrol, 2023, 34(11): 1776-1792. |
| [48] | Santarsiero D, Aiello S. The complement system in kidney transplantation[J]. Cells, 2023, 12(5):791. |
| [49] | Vonbrunn E, Büttner-Herold M, Amann K, et al. Complement inhibition in kidney transplantation: where are we now?[J]. BioDrugs, 2023, 37(1): 5-19. |
| [50] | Rovin BH, Adler SG, Barratt J, et al. KDIGO 2021 clinical practice guideline for the management of glomerular diseases[J]. Kidney International, 2021, 100(4): S1-S276. |
| [51] | Rosenblad T, Rebetz J, Johansson M, et al. Eculizumab treatment for rescue of renal function in IgA nephropathy[J]. Pediatr Nephrol, 2014, 29(11): 2225-2228. |
| [52] | McNamara LA, Topaz N, Wang X, et al. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine[J]. MMWR Morb Mortal Wkly Rep, 2017, 66(27): 734-737. |
| [53] | Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children[J]. Pediatr Nephrol, 2016, 31(1): 15-39. |
| [54] | Antonucci L, Thurman JM, Vivarelli M. Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities[J]. Pediatr Nephrol, 2024, 39(5): 1387-1404. |
| [55] | Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome na?ve to complement inhibitor treatment[J]. Kidney Int, 2020, 97(6): 1287-1296. |
| [56] | Lee A. Avacopan: first approval[J]. Drugs, 2022, 82(1): 79-85. |
| [57] | Schaefer F, Ardissino G, Ariceta G, et al. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome[J]. Kidney Int, 2018, 94(2): 408-418. |
| [58] | Lapeyraque AL, Bitzan M, Al-Dakkak I, et al. Clinical Characteristics and outcome of Canadian patients diagnosed with atypical hemolytic uremic syndrome[J]. Can J Kidney Health Dis, 2020, 7: 2054358119897229. |
/
| 〈 |
|
〉 |
