Pediatric Nephrotic Syndrome Medication

  • Author: Jerome C Lane, MD; Chief Editor: Craig B Langman, MD   more...
 
Updated: Nov 11, 2011
 

Medication Summary

Prednisone is the first-line therapy for children with nephrotic syndrome. Other immunosuppressive medications may be useful in those whose symptoms fail to respond to standard corticosteroid therapy or in those who have frequent relapses.

Next

Glucocorticoids

Class Summary

All glucocorticoids are effective; however, prednisone or prednisolone is used most commonly. Their specific mode of action in nephrotic syndrome is unknown.

View full drug information

Prednisone

 

Prednisone is a delta1-derivative of naturally occurring adrenocortical steroids. It suppresses key components of the immune system.

View full drug information

Prednisolone (Orapred, Pediapred, Prelone)

 

Prednisolone is a delta1-derivative of the naturally occurring adrenocortical steroids. It suppresses key components of the immune system.

Previous
Next

Diuretics

Class Summary

Diuretics promote excretion of water and electrolytes by the kidneys. These agents are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.

View full drug information

Furosemide (Lasix)

 

Furosemide is used when symptomatic edema occurs. It increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.

View full drug information

Metolazone (Zaroxolyn)

 

Metolazone increases excretion of sodium, water, potassium and hydrogen ions by inhibiting reabsorption of sodium in the distal tubules. Metolazone may be used to augment diuretic response during treatment with furosemide.

Previous
Next

Plasma protein

Class Summary

This agent is used to supplement diuresis in patients with edema. It increases oncotic pressure and thereby promotes a fluid shift from interstitial tissues.

View full drug information

Albumin (Albuminar, Buminate, Flexbumin, Plasbumin)

 

Albumin raises oncotic pressure and thus supplements the diuretic effect of furosemide.

Previous
Next

Immunosuppressive agents

Class Summary

This agent is used to supplement diuresis in patients with edema. It increases oncotic pressure and thereby promotes a fluid shift from interstitial tissues.

View full drug information

Cyclophosphamide

 

Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. It is chemically related to nitrogen mustards. In the liver, this agent is biotransformed by the cytochrome P-450 system to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

The mechanism of action of cyclophosphamide in autoimmune diseases is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, cyclophosphamide affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, it affects T cell functions.

Cyclophosphamide has been successfully used in conditions that require immunosuppression. It is highly effective for frequently relapsing steroid-sensitive nephrotic syndrome; half of the children enter a prolonged remission. Researchers have formulated various protocols for different renal pathological lesions.

View full drug information

Cyclosporine (Sandimmune, Neoral, Gengraf)

 

Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for various organs.

This agent is a specific modulator of T-cell replication and activity. It depresses cell-mediated immune responses by inhibiting helper T-cell function. It may produce preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of the cell cycle. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure. This agent has minimal activity against B cells.

Cyclosporine binds to cyclophilin, an intracellular protein, which in turn prevents formation of interleukin 2 and the subsequent recruitment of activated T cells.

The bioavailability of cyclosporine averages about 30%, but this varies markedly between individual patients.

View full drug information

Tacrolimus (Prograf)

 

Tacrolimus is an immunomodulator produced by the bacterium Streptomyces tsukubaensis. Its mechanism of action is similar to that of cyclosporine. This agent is primarily used in transplant recipients, but is also used in Behçet disease to treat uveitis.

View full drug information

Mycophenolate mofetil (CellCept, Myfortic)

 

This agent inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production.

Previous
 
Contributor Information and Disclosures
Author

Jerome C Lane, MD  Assistant Professor of Pediatrics, Northwestern University, The Feinberg School of Medicine; Attending Physician, Department of Pediatrics, Division of Kidney Diseases, Children's Memorial Hospital

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, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Additional Contributors

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. 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. Jun 2000;105(6):1242-9. [Medline].

  2. [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. Feb 1978;13(2):159-65. [Medline].

  3. [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. Apr 1981;98(4):561-4. [Medline].

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

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

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

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

  8. 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. Oct 2008;19(10):1871-8. [Medline].

  9. 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. Dec 2009;76(12):1268-76. [Medline].

  10. 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. Oct 2008;40(10):1175-84. [Medline].

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

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

  13. 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. Mar 2005;16(3):629-37. [Medline].

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

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

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

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

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

  19. Niaudet P. Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children. In: Avner E, Harmon W and Niaudet P. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2004:chap 27.

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

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

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

  23. 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. Jun 20 1970;760(1):1299-302. [Medline].

  24. 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. May 2007;43(5):337-41. [Medline].

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

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

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

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

  29. 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. Apr 1993;152(4):357-61. [Medline].

  30. 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. May 1997;8(5):769-76. [Medline].

  31. 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. Jun 2010;156(6):965-71. [Medline].

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  48. 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. May 2009;53(5):760-9. [Medline].

  49. 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. Jan 2008;31(1):90-4. [Medline].

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

  51. 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. Nov 2006;1(6):1173-8. [Medline].

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

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

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

  55. 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. Jul 1990;4(4):303-7. [Medline].

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

  57. 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. Aug 2008;23(8):1269-79. [Medline].

  58. 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. Jun 2011;6(6):1308-15. [Medline]. [Full Text].

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

  60. 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. Dec 2010;5(12):2207-12. [Medline]. [Full Text].

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

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

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

  64. 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. Sep 2009;24(9):2938-40. [Medline].

  65. 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. Aug 2009;24(8):1583-6. [Medline].

  66. Immunization in Special Clinical Circumstances. In: 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.

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

 
Previous
Next
 
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).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.