Renal glomerular lesions in children with juvenile rheumatoid arthritis (literature review)




juvenile rheumatoid arthritis, children, glomerulonephritis


The literature review describes the different forms of glomerulonephritis (GN) in children with polyarticular and systemic forms of juvenile rheumatoid arthritis (JRA). In the available literature, there are 21 clinical cases of GN: ANCA-associated GN, mesangial proliferative GN, including IgA- and IgM-nephropathy, membranous nephropathy, focal-segmental glomerulosclerosis, minimal change disease, and extracapillary GN. The mechanism of glomerular lesions in JRA is explained by hyperproduction of pro-inflammatory cytokines and by nephrotoxic action of basal anti-inflammatory medications. The clinical manifestations and the effectiveness of treatment of each variant of GN in children with JRA were analyzed in detail. Most publications are devoted to ANCA-associated GN, which developed in patients with a torpid course and a high activity of polyarticular and systemic forms of JRA. The peculiarity of ANCA-associated GN was the presence of hypercreatininemia and in almost half of cases the development of terminal renal failure, despite conducted immunosuppressive therapy. Single cases of other variants of GN were described more than 10 years ago. Proteinuria and the rare nephrotic syndrome were clinically observed, which was the reason for intravital renal morphological examination. Immunosuppressive therapy was effective in mesangial proliferative GN and minimal change disease. All cases of focal-segmental glomerulosclerosis, extracapillary GN were accompanied by the formation of terminal renal failure. Favorable prognosis appeared in children with drug-induced membranous nephropathy after their withdrawal. There are publications on a positive therapeutic effect of genetically engineered biological drugs in ANCA-associated GN, IgM-nephropathy, and a hormone-resistant variant of MCD in children with JRA.


Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004 Feb;31(2):390-392.

Barut K, Adrovic A, Şahin S, Kasapçopur Ö. Juvenile Idiopathic Arthritis. Balkan Med J. 2017 Apr 5;34(2):90-101. doi:10.4274/balkanmedj.2017.0111.

Lee JJY, Schneider R. Systemic Juvenile Idiopathic Arthritis. Pediatr Clin North Am. 2018 Aug;65(4):691-709. doi:10.1016/j.pcl.2018.04.005.

Crayne CB, Beukelman T. Juvenile Idiopathic Arthritis: Oligoarthritis and Polyarthritis. Pediatr Clin North Am. 2018 Aug;65(4):657-674. doi:10.1016/j.pcl.2018.03.005.

Dursun I, Yel S, Yılmaz K, Poyrazoglu H. Renal involvement in children with rheumatic diseases other than systemic vasculitis, SLE and autoinflammatory diseases. Annals of Paediatric Rheumatology. 2012;(1)2:97-105. doi:10.5455/APR.033120121350.

Sihvonen S, Korpela M, Mustonen J, Laippala P, Pasternack A. Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron Clin Pract. 2004;96(4):c107-14. doi:10.1159/000077372.

Icardi A, Araghi P, Ciabattoni M, Romano U, Lazzarini P, Bianchi G. Kidney involvement in rheumatoid arthritis. Reumatismo. 2003;55(2):76-85. doi:10.4081/reumatismo.2003.76. (in Italian).

Borysova TP, Samsonenko SV, Badogina LP. On the issue of secondary renal amyloidosis in juvenile rheumatoid arthritis in children. Zdorov`e rebenka. 2020;(15)4:252-257. doi:10.22141/2224-0551.15.4.2020.208477. (in Russian).

Gicchino MF, Di Sessa A, Guarino S, Miraglia Del Giudice E, Olivieri AN, Marzuillo P. Prevalence of and factors associated to chronic kidney disease and hypertension in a cohort of children with juvenile idiopathic arthritis. Eur J Pediatr. 2021 Feb;180(2):655-661. doi:10.1007/s00431-020-03792-4.

Delplanque M, Pouchot J, Ducharme-Bénard S, et al. AA amyloidosis secondary to adult onset Still's disease: About 19 cases. Semin Arthritis Rheum. 2020 Feb;50(1):156-165. doi:10.1016/j.semarthrit.2019.08.005.

Dhib M, Prieur AM, Courville S, et al. Crescentic glomerulonephritis in juvenile chronic arthritis. J Rheumatol. 1996 Sep;23(9):1636-1640.

Washizawa K, Wakabayashi Y. A case of juvenile rheumatoid arthritis with MPO-ANCA associated nephritis. Ryumachi. 1998 Feb;38(1):29-33. (in Japanese).

Hwang YS, Rhie Y J, Ahn SY, Kim DS, Lee JS, Jeong HJ. A Case of ANCA-associated pauci-immune crescentic glomerulonephritis in juvenile rheumatoid arthritis. Journal of the Korean Society of Pediatric Nephrology. 2005;(9)2:231-236.

Belot A, Bader-Meunier B, Niaudet P, et al. ANCA-associated glomerulonephritis in systemic-onset juvenile idiopathic arthritis. Am J Kidney Dis. 2012 Mar;59(3):439-443. doi:10.1053/j.ajkd.2011.11.002.

Heeringa P, Huugen D, Tervaert JW. Anti-neutrophil cytoplasmic autoantibodies and leukocyte-endothelial interactions: a sticky connection? Trends Immunol. 2005 Nov;26(11):561-564. doi:10.1016/

Mustila A, Korpela M, Mustonen J, et al. Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy. Arthritis Rheum. 1997 Apr;40(4):710-717. doi:10.1002/art.1780400417.

Mulder L, van Rossum M, Horst G, et al. Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis. J Rheumatol. 1997 Mar;24(3):568-575.

Bakkaloglu A, Ozen S, Saatci U, et al. Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis. Clin Rheumatol. 1999;18(4):304-307. doi:10.1007/s100670050106.

Speckmaier M, Röther E, Terreri T, et al. Prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in juvenile chronic arthritis. Clin Exp Rheumatol. 1996 Mar-Apr;14(2):211-216.

Gedalia A, Mendez EA, Craver R, Vehaskari M, Espinoza LR. Renal involvement in juvenile rheumatoid arthritis: report of two cases. Clin Rheumatol. 2001;20(2):153-156. doi:10.1007/pl00011196.

Bandin F, Merhenberger M, Modesto A, Brochard K, Decramer S. Steroid-responsive nephrotic syndrome in a child with juvenile idiopathic arthritis. Pediatr Nephrol. 2008 Apr;23(4):651-654. doi:10.1007/s00467-007-0678-9.

Voyer LE, Alvarado C, Cuttica RJ, Balestracci A, Zardini M, Lago N. Nephrotic syndrome due to immunoglobulin M mesangial glomerulonephritis preceding juvenile idiopathic arthritis. Iran J Kidney Dis. 2013 May 21;7(3):231-234.

Matsukura H, Igarashi N, Kazama T, Saito K. Concurrent occurrence of juvenile reactive arthritis and IgA nephropathy. Clin Nephrol. 2014 May;81(5):379-380. doi:10.5414/CN108200.

Kallen KJ. The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases. Biochim Biophys Acta. 2002 Nov 11;1592(3):323-343. doi:10.1016/s0167-4889(02)00325-7.

Peake NJ, Khawaja K, Myers A, et al. Interleukin-6 signalling in juvenile idiopathic arthritis is limited by proteolytically cleaved soluble interleukin-6 receptor. Rheumatology (Oxford). 2006 Dec;45(12):1485-1489. doi:10.1093/rheumatology/kel154.

Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) Immunotherapy. Cold Spring Harb Perspect Biol. 2018 Aug 1;10(8):a028456. doi:10.1101/cshperspect.a028456.

Akioka S. Interleukin-6 in juvenile idiopathic arthritis. Mod Rheumatol. 2019 Mar;29(2):275-286. doi:10.1080/14397595.2019.1574697.

Gohda T, Makita Y, Shike T, Funabiki K, Shirato I, Tomino Y. Dilazep hydrochloride, an antiplatelet drug, inhibits lipopolysaccharide-induced mouse mesangial cell IL-6 secretion and proliferation. Kidney Blood Press Res. 2001;24(1):33-38. doi:10.1159/000054203.

Su H, Lei CT, Zhang C. Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol. 2017 Apr 21;8:405. doi:10.3389/fimmu.2017.00405.

Lu H, Zhou J. HBV X gene transfection upregulates IL-1beta and IL-6 gene expression and induces rat glomerular mesangial cell proliferation. J Huazhong Univ Sci Technolog Med Sci. 2008 Jun;28(3):247-250. doi:10.1007/s11596-008-0304-5.

Kawasaki Y, Suzuki J, Sike T, et al. Bucillamine-induced nephropathy in a child with juvenile rheumatoid arthritis and Kartagener's syndrome. Pediatr Int. 2000 Jun;42(3):316-318. doi:10.1046/j.1442-200x.2000.01211.x.

Suzuki K, Tanaka H, Ito E, Waga S. Therapy-related membranous nephropathy in juvenile idiopathic arthritis with Turner syndrome. Pediatr Int. 2004 Jun;46(3):377-379. doi:10.1111/j.1442-200x.2004.01906.x.

Foster BJ, Duffy CM, Sharma AK. Systemic juvenile rheumatoid arthritis complicated by two different renal lesions. Pediatr Nephrol. 1998 Feb;12(2):113-116. doi:10.1007/s004670050416.

Gedalia A, Mendez EA, Craver R, Vehaskari M, Espinoza LR. Renal involvement in juvenile rheumatoid arthritis: report of two cases. Clin Rheumatol. 2001;20(2):153-156. doi:10.1007/pl00011196.

Varma S. Juvenile rheumatoid arthritis with focal segmental glomerulosclerosis: a rare association. Pediatr Nephrol. 2010 Oct;25(10):2189-2190. doi:10.1007/s00467-010-1504-3.

Lévy M, Prieur AM, Gubler MC, et al. Renal involvement in juvenile chronic arthritis: clinical and pathologic features. Am J Kidney Dis. 1987 Feb;9(2):138-146. doi:10.1016/s0272-6386(87)80091-4.

Kari JA, Bamashmous H, Mahan JD. Steroid-sensitive nephrotic syndrome and juvenile idiopathic arthritis. Pediatr Nephrol. 2002 Nov;17(11):975-976. doi:10.1007/s00467-002-0957-4.

Ito S, Tsutsumi A, Harada T, Inaba A, Fujinaga S, Kamei K. Long-term remission of nephrotic syndrome with etanercept for concomitant juvenile idiopathic arthritis. Pediatr Nephrol. 2010 Oct;25(10):2175-2177. doi:10.1007/s00467-010-1571-5.

Kim SH, Park SJ, Han KH, et al. Pathogenesis of minimal change nephrotic syndrome: an immunological concept. Korean J Pediatr. 2016 May;59(5):205-211. doi:10.3345/kjp.2016.59.5.205.

Otero Gilz A, Esteban J, Martínez Salgado J, Mariña G, Rodríguez Guede G. Chronic juvenile arthritis and minimal change glomerulonephritis (MCGN), the same pathogenic basis? An Med Interna. 1991 Aug;8(8):413-414. (in Spanish).

Shi D, Zhang Y, Liu D, Xu L, Tang X. Analysis of the clinical characteristics of arthritis with renal disease caused by a NPHS2 gene mutation. Clin Rheumatol. 2021 Jan 11. doi:10.1007/s10067-020-05574-7.

Menè P, Franeta AJ, Conti G, et al. Extracapillary glomerulonephritis during etanercept treatment for juvenile psoriatic arthritis. Clin Exp Rheumatol. 2010 Jan-Feb;28(1):91-93.