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Pediatric Nephrotic Syndrome Differential Diagnoses

  • Author: Jerome C Lane, MD; Chief Editor: Craig B Langman, MD  more...
 
Updated: May 16, 2016
 
 

Diagnostic Considerations

Acute kidney failure (AKF) is a rare complication of idiopathic nephrotic syndrome. Fever, rash, arthralgia and eosinophilia with a "bland" urinalysis (minimal cellular elements) in the presence of AKF are typical for acute interstitial nephritis. However, obvious clinical symptoms may be absent except for the AKF and unremarkable urinalysis. Gross hematuria, flank pain, and thrombocytopenia may be signs of renal vein thrombosis. Hemoconcentration in the patient with anasarca might indicate intravascular volume depletion.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

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.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, 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 Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Acknowledgements

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.

References
  1. Niaudet P. Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children. Avner E, Harmon W and Niaudet P. 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. [Medline].

  3. [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. [Medline].

  4. [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. [Medline].

  5. 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. [Medline].

  6. 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. [Medline].

  7. 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. [Medline].

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

  9. Niaudet P. Genetic forms of nephrotic syndrome. Pediatr Nephrol. 2004 Dec. 19(12):1313-8. [Medline].

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

  11. 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. [Medline].

  12. 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. [Medline].

  13. 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. [Medline].

  14. 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. [Medline].

  15. 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. [Medline].

  16. 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. [Medline].

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

  18. 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. [Medline].

  19. Anderson S, Komers R, Brenner BM. Renal and Systemic Manifestations of Glomerular Disease. Brenner BM. Brenner and Rector's The Kidney. 8th ed. Philadelphia: Saunders Elsvier; 2008. Chapter 26.

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

  21. 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. [Medline].

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

  23. 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. [Medline].

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

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

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

  27. 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. [Medline].

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

  29. 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. [Medline].

  30. 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. [Medline].

  31. Niaudet P. Genetic forms of nephrotic syndrome. Pediatr Nephrol. 2004 Dec. 19(12):1313-8. [Medline].

  32. 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. [Medline].

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

  34. 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. [Medline].

  35. 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. [Medline].

  36. 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. [Medline].

  37. 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. [Medline].

  38. 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. [Medline].

  39. 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. [Medline].

  40. 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. [Medline].

  41. 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. [Medline].

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

  43. Niaudet P. Steroid-Resistant Idiopathic Nephrotic Syndrome in Children. Avner E, Harmon W, and Niaudet P. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004. Chapter 28.

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

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

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

  47. 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. [Medline].

  48. 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. [Medline].

  49. 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. [Medline].

  50. 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. [Medline].

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

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

  53. 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. [Medline].

  54. 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. [Medline]. [Full Text].

  55. 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. [Medline]. [Full Text].

  56. 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. [Medline].

  57. Wang W, Xia Y, Mao J, Chen Y, Wang D, Shen H, et al. Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2012 Nov. 27(11):2073-9. [Medline].

  58. 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. [Medline].

  59. Sinha MD, MacLeod R, Rigby E, Clark AG. Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant. 2006 Jul. 21(7):1848-54. [Medline].

  60. 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. [Medline].

  61. Basu B, Mahapatra TK, Mondal N. Mycophenolate Mofetil Following Rituximab in Children With Steroid-Resistant Nephrotic Syndrome. Pediatrics. 2015 Jul. 136 (1):e132-9. [Medline].

  62. Greenbaum LA, Benndorf R, Smoyer WE. Childhood nephrotic syndrome--current and future therapies. Nat Rev Nephrol. 2012 Aug. 8(8):445-58. [Medline].

  63. Hodson EM, Habashy D, Craig JC. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2006 Apr 19. CD003594. [Medline].

  64. Del Rio M, Kaskel F. Evaluation and management of steroid-unresponsive nephrotic syndrome. Curr Opin Pediatr. 2008 Apr. 20(2):151-6. [Medline].

  65. de Mello VR, Rodrigues MT, Mastrocinque TH, et al. Mycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome. Pediatr Nephrol. 2010 Mar. 25(3):453-60. [Medline].

  66. 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 Oct. 80(8):868-78. [Medline]. [Full Text].

  67. 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. [Medline].

  68. 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. [Medline].

  69. Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008 Aug. 23(8):1269-79. [Medline].

  70. 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. [Medline]. [Full Text].

  71. Haffner D, Fischer DC. Nephrotic syndrome and rituximab: facts and perspectives. Pediatr Nephrol. 2009 Aug. 24(8):1433-8. [Medline].

  72. Gulati A, Sinha A, Jordan SC, et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol. 2010 Dec. 5(12):2207-12. [Medline]. [Full Text].

  73. Chaumais MC, Garnier A, Chalard F, et al. Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol. 2009 Sep. 24(9):1753-5. [Medline].

  74. Kveder R. Therapy-resistant focal and segmental glomerulosclerosis. Nephrol Dial Transplant. 2003 Jul. 18 Suppl 5:v34-7. [Medline].

  75. Ponticelli C. Recurrence of focal segmental glomerular sclerosis (FSGS) after renal transplantation. Nephrol Dial Transplant. 2010 Jan. 25(1):25-31. [Medline].

  76. De Smet E, Rioux JP, Ammann H, Deziel C, Querin S. FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant. 2009 Sep. 24(9):2938-40. [Medline].

  77. 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. [Medline].

  78. Immunization in Special Clinical Circumstances. Pickering LK, Baker CJ, Long SS, McMillan JA. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics;

  79. Alpay H, Yildiz N, Onar A, Temizer H, Ozcay S. Varicella vaccination in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2002 Mar. 17(3):181-3. [Medline].

  80. Outlook Favorable in Relapsing Nephrotic Syndrome. Medscape. Oct 16 2014. [Full Text].

  81. Ishikura K, Yoshikawa N, Nakazato H, et al. Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial. Pediatr Nephrol. 2014 Oct 3. [Medline].

  82. Mishra OP, Abhinay A, Mishra RN, Prasad R, Pohl M. Can We Predict Relapses in Children with Idiopathic Steroid-Sensitive Nephrotic Syndrome?. J Trop Pediatr. 2013 Apr 24. [Medline].

  83. Roberti I, Vyas S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol. 2010 Jun. 25(6):1117-24. [Medline].

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Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).
 
 
 
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