Advertisement

Focal and Segmental Glomerulosclerosis (FSGS)

  • Stephanie Nguyen
  • Kuang-Yu Jen
Chapter

Abstract

Adolescents who present with nephrotic syndrome frequently have relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome and are more likely to have a renal biopsy, in which case FSGS may be diagnosed. FSGS generally features progressive glomerular scarring leading to decline of renal function and end-stage renal disease (ESRD), though with a variable clinical course depending on the underlying etiology and response to therapy.

Keywords

Focal segmental glomerulosclerosis (FSGS) Adolescents Nephrotic syndrome Steroid-resistant nephrotic syndrome Steroid-dependent nephrotic syndrome Proteinuria 

References

  1. 1.
    Ferris ME, Gipson DS, Kimmel PL, Eggers PW. Trends in treatment and outcomes of survival of adolescents initiating end-stage renal disease care in the United States of America. Pediatr Nephrol. 2006;21(7):1020–6.CrossRefGoogle Scholar
  2. 2.
    Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int. 1978;13(2):159–65.Google Scholar
  3. 3.
    The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 1981;98(4):561–4.Google Scholar
  4. 4.
    Borges FF, Shiraichi L, da Silva MPH, Nishimoto EI, Nogueira PCK. Is focal segmental glomerulosclerosis increasing in patients with nephrotic syndrome? Pediatr Nephrol. 2007;22(9):1309–13.CrossRefGoogle Scholar
  5. 5.
    Bonilla-Felix M, Parra C, Dajani T, Ferris M, Swinford RD, Portman RJ, et al. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int. 1999;55(5):1885–90.CrossRefGoogle Scholar
  6. 6.
    Braden GL, Mulhern JG, O’Shea MH, Nash SV, Ucci AA Jr, Germain MJ. Changing incidence of glomerular diseases in adults. Am J Kidney Dis. 2000;35(5):878–83.CrossRefGoogle Scholar
  7. 7.
    Haas M, Spargo BH, Coventry S. Increasing incidence of focal-segmental glomerulosclerosis among adult nephropathies: a 20-year renal biopsy study. Am J Kidney Dis. 1995;26(5):740–50.CrossRefGoogle Scholar
  8. 8.
    Kitiyakara C, Eggers P, Kopp JB. Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States. Am J Kidney Dis. 2004;44(5):815–25.CrossRefGoogle Scholar
  9. 9.
    Kim JS, Bellew CA, Silverstein DM, Aviles DH, Boineau FG, Vehaskari VM. High incidence of initial and late steroid resistance in childhood nephrotic syndrome. Kidney Int. 2005;68(3):1275–81.CrossRefGoogle Scholar
  10. 10.
    Baqi N, Singh A, Balachandra S, Ahmad H, Nicastri A, Kytinski S, et al. The paucity of minimal change disease in adolescents with primary nephrotic syndrome. Pediatr Nephrol. 1998;12(2):105–7.CrossRefGoogle Scholar
  11. 11.
    Bose B, Cattran D, Toronto Glomerulonephritis R. Glomerular diseases: FSGS. Clin J Am Soc Nephrol. 2014;9(3):626–32.CrossRefGoogle Scholar
  12. 12.
    Chapter 3: steroid-sensitive nephrotic syndrome in children. Kidney Int Suppl. 2(2):163–71.Google Scholar
  13. 13.
    Querfeld U. Should hyperlipidemia in children with the nephrotic syndrome be treated? Pediatr Nephrol. 1999;13(1):77–84.CrossRefGoogle Scholar
  14. 14.
    Trautmann A, Bodria M, Ozaltin F, Gheisari A, Melk A, Azocar M, et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol. 2015;10(4):592–600.CrossRefGoogle Scholar
  15. 15.
    Alshami A, Roshan A, Catapang M, Jöbsis JJ, Kwok T, Polderman N, et al. Indications for kidney biopsy in idiopathic childhood nephrotic syndrome. Pediatr Nephrol. 2017;32:1–9.CrossRefGoogle Scholar
  16. 16.
    Fogo AB. Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol. 2015;11(2):76–87.CrossRefGoogle Scholar
  17. 17.
    Lovric S, Ashraf S, Tan W, Hildebrandt F. Genetic testing in steroid-resistant nephrotic syndrome: when and how? Nephrol Dial Transplant. 2016;31(11):1802–13.CrossRefGoogle Scholar
  18. 18.
    Hinkes BG, Mucha B, Vlangos CN, Gbadegesin R, Liu J, Hasselbacher K, et al. Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2). Pediatrics. 2007;119(4):e907–19.CrossRefGoogle Scholar
  19. 19.
    Santín S, Bullich G, Tazón-Vega B, García-Maset R, Giménez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6(5):1139–48.CrossRefGoogle Scholar
  20. 20.
    Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26(6):1279–89.CrossRefGoogle Scholar
  21. 21.
    Stefanidis CJ, Querfeld U. The podocyte as a target: cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations. Eur J Pediatr. 2011;170(11):1377–83.CrossRefGoogle Scholar
  22. 22.
    Lipska BS, Iatropoulos P, Maranta R, Caridi G, Ozaltin F, Anarat A, et al. Genetic screening in adolescents with steroid-resistant nephrotic syndrome. Kidney Int. 2013;84(1):206–13.CrossRefGoogle Scholar
  23. 23.
    Büscher AK, Beck BB, Melk A, Hoefele J, Kranz B, Bamborschke D, et al. Rapid response to cyclosporin a and favorable renal outcome in nongenetic versus genetic steroid–resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2016;11(2):245–53.CrossRefGoogle Scholar
  24. 24.
    Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol. 2004;15(3):722–32.CrossRefGoogle Scholar
  25. 25.
    Klaassen I, Ozgoren B, Sadowski CE, Moller K, van Husen M, Lehnhardt A, et al. Response to cyclosporine in steroid-resistant nephrotic syndrome: discontinuation is possible. Pediatr Nephrol. 2015;30(9):1477–83.CrossRefGoogle Scholar
  26. 26.
    Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006;38(12):1397–405.CrossRefGoogle Scholar
  27. 27.
    Jennette JC, Olson JL, Silva FG, D’Agati VD. Heptinstall’s pathology of the kidney. 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015. 2 volumes pGoogle Scholar
  28. 28.
    D’Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43(2):368–82.CrossRefGoogle Scholar
  29. 29.
    D’Agati VD, Jennette JC, Silva FG, American Registry of Pathology., Armed Forces Institute of Pathology (U.S.). Non-neoplastic kidney diseases. Washington, DC: American Registry of Pathology in collaboration with the Armed Forces Institute of Pathology; 2005. p. xvii. 721 p. pGoogle Scholar
  30. 30.
    D’Agati VD, Alster JM, Jennette JC, Thomas DB, Pullman J, Savino DA, et al. Association of histologic variants in FSGS clinical trial with presenting features and outcomes. Clin J Am Soc Nephrol. 2013;8(3):399–406.CrossRefGoogle Scholar
  31. 31.
    Stokes MB, Markowitz GS, Lin J, Valeri AM, D’Agati VD. Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int. 2004;65(5):1690–702.CrossRefGoogle Scholar
  32. 32.
    Howie AJ. Changes at the glomerular tip: a feature of membranous nephropathy and other disorders associated with proteinuria. J Pathol. 1986;150(1):13–20.CrossRefGoogle Scholar
  33. 33.
    Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, et al. Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol. 2006;21(3):344–9.CrossRefGoogle Scholar
  34. 34.
    Bagga A, Mudigoudar BD, Hari P, Vasudev V. Enalapril dosage in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2004;19(1):45–50.CrossRefGoogle Scholar
  35. 35.
    Yi Z, Li Z, Wu XC, He QN, Dang XQ, He XJ. Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol. 2006;21(7):967–72.CrossRefGoogle Scholar
  36. 36.
    Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;124(2):747–57.CrossRefGoogle Scholar
  37. 37.
    McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM. Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 2001;16(12):1040–4.CrossRefGoogle Scholar
  38. 38.
    Lombel RM, Gipson DS, Hodson EM. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013;28(3):415–26.CrossRefGoogle Scholar
  39. 39.
    Lombel RM, Hodson EM, Gipson DS. Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatr Nephrol. 2013;28(3):409–14.CrossRefGoogle Scholar
  40. 40.
    Pravitsitthikul N, Willis N, Hodson EM, Craig JC. Non-corticosteroid immunosuppressive medications for steroidsensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2013;(10):CD002290.  https://doi.org/10.1002/14651858.CD002290.pub4. Pages 1–121.
  41. 41.
    Chiu Mok C, Sing Lau C, Woon Sing Wong R. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheumatism. 1998;41(5):831–7.CrossRefGoogle Scholar
  42. 42.
    Ioannidis JPA, Katsifis GE, Tzioufas AG, Moutsopoulos HM. Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus. J Rheumatol. 2002;29(10):2129–35.PubMedGoogle Scholar
  43. 43.
    Wetzels JFM. Cyclophosphamide-induced gonadal toxicity: a treatment dilemma in patients with lupus nephritis? Neth J Med. 2004;62(10):347–52.PubMedGoogle Scholar
  44. 44.
    Latta K, von Schnakenburg C, Ehrich JHH. A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol. 2001;16(3):271–82.CrossRefGoogle Scholar
  45. 45.
    Ishikura K, Ikeda M, Hattori S, Yoshikawa N, Sasaki S, Iijima K, et al. Effective and safe treatment with cyclosporine in nephrotic children: a prospective, randomized multicenter trial. Kidney Int. 2008;73(10):1167–73.CrossRefGoogle Scholar
  46. 46.
    Niaudet P. Comparison of cyclosporin and chlorambucil in the treatment of steroid-dependent idiopathic nephrotic syndrome: a multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol. 1992;6(1):1–3.CrossRefGoogle Scholar
  47. 47.
    Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, et al. Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant. 1993;8(12):1326–32.PubMedGoogle Scholar
  48. 48.
    Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, et al. Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int. 2002;61(5):1801–5.CrossRefGoogle Scholar
  49. 49.
    Myers BD, Sibley R, Newton L, Tomlanovich SJ, Boshkos C, Stinson E, et al. The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int. 1988;33(2):590–600.CrossRefGoogle Scholar
  50. 50.
    Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M, et al. Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol. 2015;26(9):2259–66.CrossRefGoogle Scholar
  51. 51.
    Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011;6(6):1308–15.CrossRefGoogle Scholar
  52. 52.
    Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, et al. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2014;384(9950):1273–81.CrossRefGoogle Scholar
  53. 53.
    Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, et al. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008;23(8):1269.CrossRefGoogle Scholar
  54. 54.
    Ravani P, Bonanni A, Rossi R, Caridi G, Ghiggeri GM. Anti-CD20 antibodies for idiopathic nephrotic syndrome in children. Clin J Am Soc Nephrol. 2016;11(4):710–20.CrossRefGoogle Scholar
  55. 55.
    Chaumais M-C, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, et al. Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol. 2009;24(9):1753–5.CrossRefGoogle Scholar
  56. 56.
    Grenda R, Jarmużek W, Rubik J, Migdał M, Pronicki M. Fatal rituximab-associated lung injury syndrome in a patient treated with rituximab for recurrence of post-transplant nephrotic syndrome. Pediatr Transplant. 2015;19(5):E115–E20.CrossRefGoogle Scholar
  57. 57.
    Bitzan M, Anselmo M, Carpineta L. Rituximab (B-cell depleting antibody) associated lung injury (RALI): a pediatric case and systematic review of the literature. Pediatr Pulmonol. 2009;44(9):922–34.CrossRefGoogle Scholar
  58. 58.
    Niaudet P. Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr. 1994;125(6 Pt 1):981–6.CrossRefGoogle Scholar
  59. 59.
    Hahn D, Hodson EM, Willis NS, Craig JC. Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP). Cochrane Database Syst Rev. 2015;(8):CD005128.  https://doi.org/10.1002/14651858.CD005128.pub3. Pages 1–78.
  60. 60.
    Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 2011;80(8):868–78.CrossRefGoogle Scholar
  61. 61.
    Garin EH, Orak JK, Hiott KL, Sutherland SE. Cyclosporine therapy for steroid-resistant nephrotic syndrome. A controlled study. Am J Dis Child. 1988;142(9):985–8.CrossRefGoogle Scholar
  62. 62.
    Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Rivolta E, Rinaldi S, et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int. 1993;43(6):1377–84.CrossRefGoogle Scholar
  63. 63.
    Lieberman KV, Tejani A. A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. J Am Soc Nephrol. 1996;7(1):56–63.PubMedGoogle Scholar
  64. 64.
    Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A. Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis. 2009;53(5):760–9.CrossRefGoogle Scholar
  65. 65.
    Gulati A, Sinha A, Gupta A, Kanitkar M, Sreenivas V, Sharma J, et al. Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome. Kidney Int. 2012;82(10):1130–5.CrossRefGoogle Scholar
  66. 66.
    Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, et al. Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol. 2012;23(6):1117–24.CrossRefGoogle Scholar
  67. 67.
    Basu B. Ofatumumab for rituximab-resistant nephrotic syndrome. N Engl J Med. 2014;370(13):1268–70.CrossRefGoogle Scholar
  68. 68.
    Bonanni A, Rossi R, Murtas C, Ghiggeri GM. Low-dose of atumumab for rituximab-resistant nephrotic syndrome. BMJ Case Rep. 2015:Published online 16 Sep 2015,  https://doi.org/10.1136/bcr-2015-210208.
  69. 69.
    Wang CS, Liverman RS, Garro R, George RP, Glumova A, Karp A, et al. Ofatumumab for the treatment of childhood nephrotic syndrome. Pediatr Nephrol. 2017;32(5):835–41.CrossRefGoogle Scholar
  70. 70.
    Yu CC, Fornoni A, Weins A, Hakroush S, Maiguel D, Sageshima J, et al. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med. 2013;369(25):2416–23.CrossRefGoogle Scholar
  71. 71.
    Hattori M, Chikamoto H, Akioka Y, Nakakura H, Ogino D, Matsunaga A, et al. A combined low-density lipoprotein apheresis and prednisone therapy for steroid-resistant primary focal segmental glomerulosclerosis in children. Am J Kidney Dis. 2003;42(6):1121–30.CrossRefGoogle Scholar
  72. 72.
    Moriarty PM. Lipoprotein apheresis: present and future uses. Curr Opin Lipidol. 2015;26(6):544–52.CrossRefGoogle Scholar
  73. 73.
    Abrantes MM, Cardoso LS, Lima EM, Penido Silva JM, Diniz JS, Bambirra EA, et al. Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis. Pediatr Nephrol. 2006;21(7):1003–12.CrossRefGoogle Scholar
  74. 74.
    Silverstein DM, Craver R. Presenting features and short-term outcome according to pathologic variant in childhood primary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2(4):700–7.CrossRefGoogle Scholar
  75. 75.
    Schwartz MM, Evans J, Bain R, Korbet SM. Focal segmental glomerulosclerosis: prognostic implications of the cellular lesion. J Am Soc Nephrol. 1999;10(9):1900–7.PubMedGoogle Scholar
  76. 76.
    Singh HK, Baldree LA, McKenney DW, Hogan SL, Jennette JC. Idiopathic collapsing glomerulopathy in children. Pediatr Nephrol. 2000;14(2):132–7.CrossRefGoogle Scholar
  77. 77.
    Huang K, Ferris ME, Andreoni KA, Gipson DS. The differential effect of race among pediatric kidney transplant recipients with focal segmental glomerulosclerosis. Am J Kidney Dis. 2004;43(6):1082–90.CrossRefGoogle Scholar
  78. 78.
    Tejani A, Stablein DH. Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol. 1992;2(12 Suppl):S258–63.PubMedGoogle Scholar
  79. 79.
    Nehus EJ, Goebel JW, Succop PS, Abraham EC. Focal segmental glomerulosclerosis in children: multivariate analysis indicates that donor type does not alter recurrence risk. Transplantation. 2013;96(6):550–4.CrossRefGoogle Scholar
  80. 80.
    Trautmann A, Bodria M, Ozaltin F, Gheisari A, Melk A, Azocar M, et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet Registry Cohort. Clin J Am Soc Nephrol. 2015;10(4):592–600.CrossRefGoogle Scholar
  81. 81.
    Baum MA, Ho M, Stablein D, Alexander SR, North American Pediatric Renal Transplant Cooperative S. Outcome of renal transplantation in adolescents with focal segmental glomerulosclerosis. Pediatr Transplant. 2002;6(6):488–92.CrossRefGoogle Scholar
  82. 82.
    Guan I, Singer P, Frank R, Chorny N, Infante L, Sethna CB. Role of race in kidney transplant outcomes in children with focal segmental glomerulosclerosis. Pediatr Transplant. 2016;20(6):790–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PediatricsUC Davis Children’s HospitalSacramentoUSA
  2. 2.Department of Pathology and Laboratory MedicineUC Davis School of MedicineSacramentoUSA

Personalised recommendations