Difficult-to-treat idiopathic nephrotic syndrome: established drugs, open questions and future options

Pediatric Nephrology

Volumn 33, Issue 10, 2018, Pages 1641-1649

  Kemper, Markus J ^a   Valentin, Lisa ^a   van Husen, Michael ^b  

^a Asklepios Medical School   (Germany)

^b Christliches Kinderhospital Osnabrück   (Germany)

Author keywords

FSGS; Immunosuppression biologicals; Ofatumumab; Rituximab; Steroid resistant nephrotic syndrome; Steroid sensitive nephrotic syndrome

Indexed keywords

ABATACEPT; ADALIMUMAB; CALCINEURIN INHIBITOR; CORTICOTROPIN; CYCLOSPORINE; FRESOLIMUMAB; GALACTOSE; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2 ANTIBODY; MYCOPHENOLATE MOFETIL; OFATUMUMAB; RITUXIMAB; TACROLIMUS; UNCLASSIFIED DRUG; VITAMIN D; BIOLOGICAL FACTOR; GLUCOCORTICOID; MYCOPHENOLIC ACID;

ADRENAL CORTEX HYPERFUNCTION; ALLERGIC REACTION; ASTHMA; BRONCHOSPASM; CHILL; CHRONIC KIDNEY FAILURE; CONGENITAL NEPHROTIC SYNDROME; DIET THERAPY; DIZZINESS; DRUG EFFICACY; DRUG MECHANISM; DYSPNEA; EDEMA; END STAGE RENAL DISEASE; FEVER; FOCAL GLOMERULOSCLEROSIS; GENETICS; GINGIVA HYPERPLASIA; GRANULOCYTOPENIA; HIGH RISK PATIENT; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPERTRICHOSIS; HYPOTENSION; IMMUNE SYSTEM; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INSOMNIA; MOOD DISORDER; NEPHROTIC SYNDROME; NEPHROTOXICITY; NONHUMAN; PERIPHERAL EDEMA; PRIORITY JOURNAL; PROGNOSIS; RELAPSE; REMISSION; REVIEW; RHINOPHARYNGITIS; SORE THROAT; STEROID SENSITIVE NEPHROTIC SYNDROME; URTICARIA; VITAMIN D DEFICIENCY; VITAMIN SUPPLEMENTATION; CHILD; DRUG RESISTANCE; IMMUNOLOGY; PATHOLOGY; PROCEDURES; RECURRENT DISEASE; SECONDARY PREVENTION; TREATMENT OUTCOME;

BIOLOGICAL FACTORS; CALCINEURIN INHIBITORS; CHILD; DRUG RESISTANCE; GLUCOCORTICOIDS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MYCOPHENOLIC ACID; NEPHROTIC SYNDROME; PROGNOSIS; RECURRENCE; REMISSION INDUCTION; SECONDARY PREVENTION; TREATMENT OUTCOME;

EID: 85028864534     PISSN: 0931041X     EISSN: 1432198X     Source Type: Journal    
DOI: 10.1007/s00467-017-3780-7     Document Type: Review

References (50)

1. Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, Engelmann S, Vega-Warner V, Fang H, Halbritter J, Somers MJ, Tan W, Shril S, Fessi I, Lifton RP, Bockenhauer D, El-Desoky S, Kari JA, Zenker M, Kemper MJ, Mueller D, Fathy HM, Soliman NA, SNRS Study Group, Hildebrandt F (2015) A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 26:1279–1289
2. Hodson EM, Willis NS, Craig JC (2007) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev (4):CD001533
3. Teeninga N (2012) Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol 24:149–159
4. Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, Ishikura K, Hataya H, Honda M, Ito S, Shima Y, Kaito H, Nozu K, Nakamura H, Igarashi T, Ohashi Y, Iijima K, Japanese Study Group of Kidney Disease in Children (2015) A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int 87:225–232
5. Hoyer PF, Brodeh J (2006) Initial treatment of idiopathic nephrotic syndrome in children: prednisone versus prednisone plus cyclosporine a: a prospective, randomized trial. J Am Soc Nephrol 17:1151–1157
6. Gruppen M, Davin J, Bouts A (2016) Levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome: results of a multi-center, double-blind, placebo-controlled, randomized clinical trial. Pediatr Nephrol 31:1753
7. Abeyagunawardena AS, Karunadasa U, Jayaweera H, Thalgahagoda S, Tennakoon S, Abeyagunawardena S (2017) Efficacy of higher-dose levamisole in maintaining remission in steroid-dependent nephrotic syndrome. Pediatr Nephrol 32:1363–1367
8. Van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892
9. Gellermann J, Weber L, Pape L, Tonshoff B, Hoyer P, Querfeld U, Gesellschaft für Pädiatrische Nephrologie (2013) Mycophenolate mofetil versus cyclosporin a in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697
10. Sinha A, Gupta A, Kalaivani M, Hari P, Dinda AK, Bagga A (2017) Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome. Kidney Int 92:248–267
11. Kemper MJ, Lehnhardt A, Zawischa A, Oh J (2014) Is rituximab effective in childhood nephrotic syndrome? Yes and no. Pediatr Nephrol 29:1305–1311
12. Iijima K, Sako M, Nozu K (2015) Rituximab treatment for nephrotic syndrome in children. Curr Pediatr Rep 3:71–77
13. Iijima K, Sako M, Nozu K (2017) Rituximab for nephrotic syndrome in children. Clin Exp Nephrol 21:193–202
14. Sinha A, Bhatia D, Gulati A, Rawat M, Dinda AK, Hari P, Bagga A (2015) Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome. Nephrol Dial Transplant 30:96–106
15. Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dotsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27:1910–1915
16. Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y, Rituximab for Childhood-onset Refractory Nephrotic Syndrome Study Group (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384:1273–1281
17. Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328
18. Sellier-Leclerc AL, Baudouin V, Kwon T, Macher MA, Guerin V, Lapillonne H, Deschenes G, Ulinski T (2012) Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood—follow-up after CD19 recovery. Nephrol Dial Transplant 27:1083–1089
19. Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Rava L, Ruggiero B, Emma F, Vivarelli M (2016) B cell reconstitution after rituximab treatment in idiopathic nephrotic syndrome. J Am Soc Nephrol 27:1811–1822
20. Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, Sako M, Iijima K (2013) Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome. Pediatr Nephrol 28:257–264
21. Dotsch J, Muller-Wiefel DE, Kemper MJ (2008) Rituximab: is replacement of cyclophosphamide and calcineurin inhibitors in steroid-dependent nephrotic syndrome possible? Pediatr Nephrol 23:3–7
22. Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M, Pasini A, Montini G, Edefonti A, Belingheri M, De Giovanni D, Barbano G, Degl'Innocenti L, Scolari F, Murer L, Reiser J, Fornoni A, Ghiggeri GM (2015) Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol 26:2259–2266
23. Tsutsumi Y, Kanamori H, Mori A, Tanaka J, Asaka M, Imamura M, Masauzi N (2005) Reactivation of hepatitis B virus with rituximab. Expert Opin Drug Saf 4:599–608
24. Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschenes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755
25. Kamei K, Okada M, Sato M, Fujimaru T, Ogura M, Nakayama M, Kaito H, Iijima K, Ito S (2014) Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome. Pediatr Nephrol 29:1181–1187
26. Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Hogan SL, Middleton JP, Vehaskari VM, Flynn PA, Powell LM, Vento SM, McMahan JL, Siegel N, D’Agati VD, Friedman AL (2011) Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 80:868–878
27. Plank C, Kalb V, Hinkes B, Hildebrandt F, Gefeller O, Rascher W (2008) Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome—a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie. Pediatr Nephrol 23:1483
28. Büscher AK, Kranz B, Büscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Broking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 5:2075–2084
29. Klaassen I, Ozgoren B, Sadowski CE, Moller K, van Husen M, Lehnhardt A, Timmermann K, Freudenberg F, Helmchen U, Oh J, Kemper MJ (2015) Response to cyclosporine in steroid-resistant nephrotic syndrome: discontinuation is possible. Pediatr Nephrol 30:1477–1483
30. Bagga A, Sinha A, Moudgil A (2007) Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 356:2751–2752
31. Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, Benetti E, Murtas C, Messina G, Massella L, Porcellini MG, Montagna M, Regazzi M, Scolari F, Ghiggeri GM (2012) Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol 23:1117–1124
32. Basu B, Mahapatra TK, Mondal N (2015) Mycophenolate mofetil following rituximab in children with steroid-resistant nephrotic syndrome. Pediatrics 136:e132–e139
33. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938
34. Fornoni A, Sageshima J, Wei C, Merscher-Gomez S, Aguillon-Prada R, Jauregui AN, Li J, Mattiazzi A, Ciancio G, Chen L, Zilleruelo G, Abitbol C, Chandar J, Seeherunvong W, Ricordi C, Ikehata M, Rastaldi MP, Reiser J, Burke GW 3rd (2011) Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci Transl Med 3:85ra46
35. Büscher AK, Beck BB, Melk A, Hoefele J, Kranz B, Bamborschke D, Baig S, Lange-Sperandio B, Jungraithmayr T, Weber LT, Kemper MJ, Tonshoff B, Hoyer PF, Konrad M, Weber S, German Pediatric Nephrology A (2016) Rapid response to Cyclosporin A and favorable renal outcome in nongenetic versus genetic steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 11:245–253
36. Basu B (2014) Ofatumumab for rituximab-resistant nephrotic syndrome. N Engl J Med 370:1268–1270
37. Ravani P, Bonanni A, Ghiggeri GM (2017) Randomised controlled trial comparing ofatumumab to rituximab in children with steroid-dependent and calcineurin inhibitor-dependent idiopathic nephrotic syndrome: study protocol. BMJ Open 7:e013319
38. Vivarelli M, Colucci M, Bonanni A, Verzani M, Serafinelli J, Emma F, Ghiggeri G (2017) Ofatumumab in two pediatric nephrotic syndrome patients allergic to rituximab. Pediatr Nephrol 32:181–184
39. Bonanni A, Bertelli R, Rossi R, Bruschi M, Di Donato A, Ravani P, Ghiggeri GM (2015) A pilot study of IL2 in drug-resistant idiopathic nephrotic syndrome. PLoS One 10:e0138343
40. Trachtman H, Fervenza FC, Gipson DS, Heering P, Jayne DR, Peters H, Rota S, Remuzzi G, Rump LC, Sellin LK, Heaton JP, Streisand JB, Hard ML, Ledbetter SR, Vincenti F (2011) A phase 1, single-dose study of fresolimumab, an anti-TGF-beta antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int 79:1236–1243
41. Yu CC, Fornoni A, Weins A, Hakroush S, Maiguel D, Sageshima J, Chen L, Ciancio G, Faridi MH, Behr D, Campbell KN, Chang JM, Chen HC, Oh J, Faul C, Arnaout MA, Fiorina P, Gupta V, Greka A, Burke GW 3rd, Mundel P (2013) Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 369:2416–2423
42. Delville M, Baye E, Durrbach A, Audard V, Kofman T, Braun L, Olagne J, Nguyen C, Deschenes G, Moulin B, Delahousse M, Kesler-Roussey G, Beaudreuil S, Martinez F, Rabant M, Grimbert P, Gallazzini M, Terzi F, Legendre C, Canaud G (2016) B7-1 blockade does not improve post-transplant nephrotic syndrome caused by recurrent FSGS. J Am Soc Nephrol 27:2520–2527
43. Lieberman KV, Pavlova-Wolf A (2017) Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance. J Nephrol 30:35–44
44. Kittanamongkolchai W, Cheungpasitporn W, Zand L (2016) Efficacy and safety of adrenocorticotropic hormone treatment in glomerular diseases: a systematic review and meta-analysis. Clin Kidney J 9:387–396
45. Madan A, Mijovic-Das S, Stankovic A, Teehan G, Milward AS, Khastgir A (2016) Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective case series. BMC Nephrol 17:37
46. Trachtman H, Vento S, Herreshoff E, Radeva M, Gassman J, Stein DT, Savin VJ, Sharma M, Reiser J, Wei C, Somers M, Srivastava T, Gipson DS (2015) Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group. BMC Nephrol 16:111
47. Lemley KV, Faul C, Schramm K, Meyers K, Kaskel F, Dell KM, Gipson DS, Gibson K, Trachtman H (2016) The effect of a gluten-free diet in children with difficult-to-manage nephrotic syndrome. Pediatrics. 138(1):e20154528. 10.1542/peds.2015-4528
48. Sandberg DH, Bernstein CW, McIntosh RM, Carr R, Strauss J (1977) Severe steroid-responsive nephrosis associated with hypersensitivity. Lancet 1:388–391
49. Deng J, Zheng X, Xie H, Chen L (2017) Calcitriol in the treatment of IgA nephropathy with non-nephrotic range proteinuria: a meta-analysis of randomized controlled trials. Clin Nephrol 87:21–27
50. Banerjee S, Basu S, Sengupta J (2013) Vitamin D in nephrotic syndrome remission: a case-control study. Pediatr Nephrol 28:1983–1989