Pediatric Nephrotic Syndrome Questions & Answers

1. Niaudet P. Steroid-sensitive idiopathic nephrotic syndrome in children. Avner E, Harmon W, Niaudet P, eds. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004. chap 27.

2. Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics. 2000 Jun. 105(6):1242-9. [QxMD MEDLINE Link].

3. Lovric S, Ashraf S, Tan W, Hildebrandt F. Genetic testing in steroid-resistant nephrotic syndrome: when and how?. Nephrol Dial Transplant. 2016 Nov. 31 (11):1802-13. [QxMD MEDLINE Link].

4. [Guideline] International Study of Kidney Disease in Children (ISKDC). 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 Feb. 13(2):159-65. [QxMD MEDLINE Link].

5. [Guideline] International Study of Kidney Disease in Children (ISKDC). 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 Apr. 98(4):561-4. [QxMD MEDLINE Link].

6. Pereira Wde F, Brito-Melo GE, Guimarães FT, Carvalho TG, Mateo EC, Simões e Silva AC. The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflamm Res. 2014 Jan. 63 (1):1-12. [QxMD MEDLINE Link].

7. Kamei K, Ito S, Nozu K, et al. Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol. 2009 Jul. 24(7):1321-8. [QxMD MEDLINE Link].

8. Ravani P, Magnasco A, Edefonti A, 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 Jun. 6(6):1308-15. [QxMD MEDLINE Link]. [Full Text].

9. Iijima K, Sako M, Nozu 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 Oct 4. 384 (9950):1273-81. [QxMD MEDLINE Link].

10. Magnasco A, Ravani P, Edefonti A, et al. Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol. 2012 Jun. 23 (6):1117-24. [QxMD MEDLINE Link].

11. Kallash M, Smoyer WE, Mahan JD. Rituximab use in the management of childhood nephrotic syndrome. Front Pediatr. 2019. 7:178. [QxMD MEDLINE Link].

12. Elie V, Fakhoury M, Deschênes G, Jacqz-Aigrain E. Physiopathology of idiopathic nephrotic syndrome: lessons from glucocorticoids and epigenetic perspectives. Pediatr Nephrol. 2012 Aug. 27(8):1249-56. [QxMD MEDLINE Link].

13. van den Berg JG, Weening JJ. Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome. Clin Sci (Lond). 2004 Aug. 107(2):125-36. [QxMD MEDLINE Link].

14. Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ. Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol. 2012 Dec. 23(12):2051-9. [QxMD MEDLINE Link].

15. Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011 Jul 31. 17 (8):952-60. [QxMD MEDLINE Link].

16. Spinale JM, Mariani LH, Kapoor S, et al. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Kidney Int. 2015 Mar. 87 (3):564-74. [QxMD MEDLINE Link].

17. Kronbichler A, Saleem MA, Meijers B, Shin JI. Soluble urokinase receptors in focal segmental glomerulosclerosis: a review on the scientific point of view. J Immunol Res. 2016. 2016:2068691. [QxMD MEDLINE Link].

18. Coleman JE, Watson AR. Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. Pediatr Nephrol. 1996 Apr. 10(2):171-4. [QxMD MEDLINE Link].

19. Uy N, Graf L, Lemley KV, Kaskel F. Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota. Pediatr Res. 2015 Jan. 77 (1-2):252-5. [QxMD MEDLINE Link].

20. Niaudet P. Genetic forms of nephrotic syndrome. Pediatr Nephrol. 2004 Dec. 19(12):1313-8. [QxMD MEDLINE Link].

21. Caridi G, Trivelli A, Sanna-Cherchi S, Perfumo F, Ghiggeri GM. Familial forms of nephrotic syndrome. Pediatr Nephrol. 2010 Feb. 25(2):241-52. [QxMD MEDLINE Link].

22. Benoit G, Machuca E, Antignac C. Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations. Pediatr Nephrol. 2010 Sep. 25(9):1621-32. [QxMD MEDLINE Link].

23. Philippe A, Nevo F, Esquivel EL, Reklaityte D, Gribouval O, Tete MJ. Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008 Oct. 19(10):1871-8. [QxMD MEDLINE Link].

24. Santin S, Garcia-Maset R, Ruiz P, Gimenez I, Zamora I, Pena A. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis. Kidney Int. 2009 Dec. 76(12):1268-76. [QxMD MEDLINE Link].

25. Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet. 2008 Oct. 40(10):1175-84. [QxMD MEDLINE Link].

26. Kronenberg F. APOL1 variants and kidney disease. There is no such thing as a free lunch. Nephrol Dial Transplant. 2011 Mar. 26(3):775-8. [QxMD MEDLINE Link].

27. Mele C, Iatropoulos P, Donadelli R, Calabria A, Maranta R, Cassis P. MYO1E mutations and childhood familial focal segmental glomerulosclerosis. N Engl J Med. 2011 Jul 28. 365(4):295-306. [QxMD MEDLINE Link].

28. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006 Mar 30. 354(13):1387-401. [QxMD MEDLINE Link].

29. Coward RJ, Foster RR, Patton D, Ni L, Lennon R, Bates DO. Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, Podocin, and CD2 associated protein in cultured human podocytes. J Am Soc Nephrol. 2005 Mar. 16(3):629-37. [QxMD MEDLINE Link].

30. Cara-Fuentes G, Clapp WL, Johnson RJ, Garin EH. Pathogenesis of proteinuria in idiopathic minimal change disease: molecular mechanisms. Pediatr Nephrol. 2016 Dec. 31 (12):2179-89. [QxMD MEDLINE Link].

31. Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal change disease. Clin J Am Soc Nephrol. 2017 Feb 7. 12 (2):332-45. [QxMD MEDLINE Link].

32. Anderson S, Komers R, Brenner BM. Renal and systemic manifestations of glomerular disease. Brenner BM, ed. Brenner and Rector's The Kidney. 8th ed. Philadelphia: Saunders Elsvier; 2008. Chapter 26.

33. Saland JM, Ginsberg H, Fisher EA. Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management. Curr Opin Pediatr. 2002 Apr. 14(2):197-204. [QxMD MEDLINE Link].

34. Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol. 2012 Mar. 7(3):513-20. [QxMD MEDLINE Link].

35. Zaffanello M, Franchini M. Thromboembolism in childhood nephrotic syndrome: a rare but serious complication. Hematology. 2007 Feb. 12(1):69-73. [QxMD MEDLINE Link].

36. Citak A, Emre S, Sâirin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol. 2000 Feb. 14(2):138-42. [QxMD MEDLINE Link].

37. Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med. 2013 Mar 7. 368(10):956-8. [QxMD MEDLINE Link].

38. Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res. 2006. 118(3):397-407. [QxMD MEDLINE Link].

39. Wu HM, Tang JL, Sha ZH, Cao L, Li YP. Interventions for preventing infection in nephrotic syndrome. Cochrane Database Syst Rev. 2004. CD003964. [QxMD MEDLINE Link].

40. Agarwal N, Phadke KD, Garg I, Alexander P. Acute renal failure in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2003 Dec. 18(12):1289-92. [QxMD MEDLINE Link].

41. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23. 362(9384):629-39. [QxMD MEDLINE Link].

42. Churg J, Habib R, White RH. Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet. 1970 Jun 20. 760(1):1299-302. [QxMD MEDLINE Link].

43. Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. 2007 May. 43(5):337-41. [QxMD MEDLINE Link].

44. Niaudet P. Genetic forms of nephrotic syndrome. Pediatr Nephrol. 2004 Dec. 19(12):1313-8. [QxMD MEDLINE Link].

45. Borges FF, Shiraichi L, da Silva MP, Nishimoto EI, Nogueira PC. Is focal segmental glomerulosclerosis increasing in patients with nephrotic syndrome?. Pediatr Nephrol. 2007 Sep. 22(9):1309-13. [QxMD MEDLINE Link].

46. Boyer O, Moulder JK, Somers MJ. Focal and segmental glomerulosclerosis in children: a longitudinal assessment. Pediatr Nephrol. 2007 Aug. 22(8):1159-66. [QxMD MEDLINE Link].

47. Ingulli E, Tejani A. Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol. 1991 Jul. 5(4):393-7. [QxMD MEDLINE Link].

48. Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr. 1993 Apr. 152(4):357-61. [QxMD MEDLINE Link].

49. Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997 May. 8(5):769-76. [QxMD MEDLINE Link].

50. Korsgaard T, Andersen RF, Joshi S, Hagstrøm S, Rittig S. Childhood onset steroid-sensitive nephrotic syndrome continues into adulthood. Pediatr Nephrol. 2019 Apr. 34 (4):641-8. [QxMD MEDLINE Link].

51. Vivarelli M, Moscaritolo E, Tsalkidis A, Massella L, Emma F. Time for initial response to steroids is a major prognostic factor in idiopathic nephrotic syndrome. J Pediatr. 2010 Jun. 156(6):965-71. [QxMD MEDLINE Link].

52. Ruth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ. Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr. 2005 Aug. 147(2):202-7. [QxMD MEDLINE Link].

53. Abeyagunawardena AS, Sebire NJ, Risdon RA, et al. Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis. Pediatr Nephrol. 2007 Feb. 22(2):215-21. [QxMD MEDLINE Link].

54. Gipson DS, Chin H, Presler TP, et al. Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol. 2006 Mar. 21(3):344-9. [QxMD MEDLINE Link].

55. Paik KH, Lee BH, Cho HY, et al. Primary focal segmental glomerular sclerosis in children: clinical course and prognosis. Pediatr Nephrol. 2007 Mar. 22(3):389-95. [QxMD MEDLINE Link].

56. Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018 Jul 7. 392 (10141):61-74. [QxMD MEDLINE Link].

57. Bensimhon AR, Williams AE, Gbadegesin RA. Treatment of steroid-resistant nephrotic syndrome in the genomic era. Pediatr Nephrol. 2019 Nov. 34 (11):2279-93. [QxMD MEDLINE Link].

58. Preston R, Stuart HM, Lennon R. Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?. Pediatr Nephrol. 2019 Feb. 34 (2):195-210. [QxMD MEDLINE Link].

59. Gipson DS, Massengill SF, Yao L, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009 Aug. 124(2):747-57. [QxMD MEDLINE Link].

60. Niaudet P. Steroid-resistant idiopathic nephrotic syndrome in children. Avner E, Harmon W, Niaudet P, eds. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004. Chapter 28.

61. Strife CF, Braun MC, West CD. Membranoproliferative glomerulonephritis. Avner E, Harmon W, Niaudet P, eds. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004. Chapter 32.

62. Makker SP. Membranous nephropathy. Avner E, Harmon W, Niaudet P, eds. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004. Chapter 33.

63. Lombel RM, Gipson DS, Hodson EM. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013 Mar. 28(3):415-26. [QxMD MEDLINE Link].

64. Prescott WA Jr, Streetman DA, Streetman DS. The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic syndrome. Ann Pharmacother. 2004 Dec. 38(12):2105-14. [QxMD MEDLINE Link].

65. Sanjad SA, al-Abbad A, al-Shorafa S. Management of hyperlipidemia in children with refractory nephrotic syndrome: the effect of statin therapy. J Pediatr. 1997 Mar. 130(3):470-4. [QxMD MEDLINE Link].

66. Rheault MN, Zhang L, Selewski DT, et al. AKI in children hospitalized with nephrotic syndrome. Clin J Am Soc Nephrol. 2015 Dec 7. 10 (12):2110-8. [QxMD MEDLINE Link].

67. Ekka BK, Bagga A, Srivastava RN. Single- versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Pediatr Nephrol. 1997 Oct. 11(5):597-9. [QxMD MEDLINE Link].

68. Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2007. (4):CD001533. [QxMD MEDLINE Link].

69. Hodson EM, Willis NS, Craig JC. Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev. 2008 Jan 23. CD002290. [QxMD MEDLINE Link].

70. Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child. 1987 Nov. 62(11):1102-6. [QxMD MEDLINE Link]. [Full Text].

71. Ueda N, Kuno K, Ito S. Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Arch Dis Child. 1990 Oct. 65(10):1147-50. [QxMD MEDLINE Link]. [Full Text].

72. Pravitsitthikul N, Willis NS, Hodson EM, Craig JC. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2013 Oct 29. CD002290. [QxMD MEDLINE Link].

73. Latta K, von Schnakenburg C, Ehrich JH. A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol. 2001 Mar. 16(3):271-82. [QxMD MEDLINE Link].

74. Wang W, Xia Y, Mao J, et al. Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2012 Nov. 27(11):2073-9. [QxMD MEDLINE Link].

75. 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 May. 53(5):760-9. [QxMD MEDLINE Link].

76. Takeuchi H, Matsuno N, Senuma K, et al. Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--. Biol Pharm Bull. 2008 Jan. 31(1):90-4. [QxMD MEDLINE Link].

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78. Larkins N, Kim S, Craig J, Hodson E. Steroid-sensitive nephrotic syndrome: an evidence-based update of immunosuppressive treatment in children. Arch Dis Child. 2016 Apr. 101 (4):404-8. [QxMD MEDLINE Link].

79. Hogg RJ, Fitzgibbons L, Bruick J, et al. Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol. 2006 Nov. 1(6):1173-8. [QxMD MEDLINE Link].

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81. Basu B, Mahapatra TK, Mondal N. Mycophenolate mofetil following rituximab in children with steroid-resistant nephrotic syndrome. Pediatrics. 2015 Jul. 136 (1):e132-9. [QxMD MEDLINE Link].

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86. Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM. Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. Pediatr Nephrol. 1990 Jul. 4(4):303-7. [QxMD MEDLINE Link].

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89. Gipson DS, Trachtman H, Kaskel FJ, et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 2011 Oct. 80(8):868-78. [QxMD MEDLINE Link]. [Full Text].

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95. Arun S, Bhatnagar S, Menon S, Saini S, Hari P, Bagga A. Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2009 Aug. 24(8):1583-6. [QxMD MEDLINE Link].

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Jerome C Lane, MD Associate Professor of Pediatrics, Northwestern University, The Feinberg School of Medicine; Attending Physician, Department of Pediatrics, Division of Kidney Diseases, Ann & Robert Lurie Children's Hospital of Chicago

Disclosure: Nothing to disclose.

Craig B Langman, MD Tenured Professor of Pediatrics, The First Isaac A Abt, MD, Professor of Kidney Diseases (Emeritus), Northwestern University, The Feinberg School of Medicine; Staff Nephrologist, The Ann and Robert H Lurie Children’s Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Clinical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Pediatric Nephrology, Association of Clinical Scientists, Cochrane Collaboration, International Bone and Mineral Society, International Conferences on Calcium Regulating Hormones, International Pediatric Nephrology Association, International Society of Nephrology, International Society of Renal Nutrition and Metabolism, Midwest Society for Pediatric Research, Pediatric Academic Societies, ROCK (Research on Calculus Kinetics) Society, Society for Pediatric Research

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Horizon Pharmaceuticals); ; Dicerna Pharmaceuticals<br/>Incyte Pharmaceuticals; Eli Lilly for: Federation bio; Dicerna pharmaceuticals.

Laurence Finberg, MD Clinical Professor, Department of Pediatrics, University of California, San Francisco, School of Medicine and Stanford University School of Medicine

Laurence Finberg, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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