Skip to main content

Advertisement

SpringerLink
Log in

Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5–18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6–13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3–13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5–18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5–5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. McEnery PT, Alexander SR, Sullican K, Tejani A (1993) Renal transplantation in children and adolescents: the 1992 Annual report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 7:711–720

    CAS  PubMed  Google Scholar 

  2. Southwest Pediatric Nephrology Group (1985) Focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome. Kidney Int 27:442–449

    PubMed  Google Scholar 

  3. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (2002) Annual report. Pediatr Nephrol (in press)

  4. Warady BA, Hebet D, Sullivan KE, Alexander SR, Tejani A (1997) Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 annual report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 11:49–64

    PubMed  Google Scholar 

  5. Srivastava T, Simon S, Alon U (1999) High incidence of focal segmental glomerulosclerosis in nephrotic syndrome in childhood. Pediatr Nephrol 13:13–18

    Google Scholar 

  6. Waldo FB, Benfield MR, Kohaut EC (1998) Therapy of focal and segmental glomerulosclerosis with methylprednisolone, cyclosporine A, and prednisone. Pediatr Nephrol 12:397–400

    Google Scholar 

  7. Singh A, Tejani C, Tejani A (1999) One-centre experience with cyclosporin in refractory nephrotic syndrome in children. Pediatr Nephrol 13:26–32

    CAS  PubMed  Google Scholar 

  8. Franke D, Zimmering M, Wolfish N, Ehrich J, Filler G (2000) Treatment of FSGS with plasma exchange and immunadsorption. Pediatr Nephrol 14:965–969

    CAS  PubMed  Google Scholar 

  9. Tune B, Lieberman E, Mendoza S (1996) Steroid-resistant nephrotic focal segmental glomerulosclerosis: a treatable disease. Pediatr Nephrol 10:772–778

    Article  CAS  PubMed  Google Scholar 

  10. Burgess E (1999) Management of focal segmental glomerulosclerosis: evidence based recommendations. Kidney Int 55:S26–S32

    Article  Google Scholar 

  11. Arbus GS, Poucell S, Bacheyie GS, Baumal R (1982) Focal segmental glomerulosclerosis with idiopathic nephrotic syndrome: three types of clinical response. J Pediatr 101:40–45

    CAS  PubMed  Google Scholar 

  12. Banfi G, Moriggi M, Sabadini E, Fellini G, D’Amico G, Ponticelli C (1991) The impact of prolonged immunosuppression on the outcome of idiopathic focal segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. Clin Nephrol 36:53–59

    CAS  PubMed  Google Scholar 

  13. Waldo FB, Kohaut EC (1987) Therapy of focal segmental glomerulosclerosis with cyclosporine A. Pediatr Nephrol 1:180–182

    CAS  PubMed  Google Scholar 

  14. Haas M, Godfrin Y, Oberbauer R, Yilmaz N, Borchhardt K, Regele H, Druml W, Derfler K, Mayer G (1998) Plasma immunoadsorption treatment in patients with primary focal segmental glomerulosclerosis. Nephrol Dial Transplant 13:2013–2016

    Article  CAS  PubMed  Google Scholar 

  15. Aviles DH, Irwin KC, Dublin LX, Vehaskari VM (1999) Aggressive treatment of severe idiopathic focal segmental glomerulosclerosis. Pediatr Nephrol 13:298–300

    Google Scholar 

  16. Mitwalli AH (1998) Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit patients with focal segmental glomerulosclerosis? Nephrol Dial Transplant 13:1524–1528

    Article  CAS  PubMed  Google Scholar 

  17. Tarshich P, Tokin JN, Remstein J, Edelmann CM Jr (1996) Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis: a report of the International Study of Kidney Disease in Children. Pediatr Nephrol 10:590–593

    Article  CAS  PubMed  Google Scholar 

  18. Geary DF, Farnie M, Thourer P, Baumal R (1984) Response to cyclophosphamide in steroid resistant focal segmental glomerulosclerosis: a reappraisal. Clin Nephrol 22:109–113

    CAS  PubMed  Google Scholar 

  19. Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB (2003) Use of mycophenolate mofetil in steroid-dependent and resistant nephrotic syndrome. Pediatr Nephrol 18:833–837

    Article  PubMed  Google Scholar 

  20. Beaufils H, Alphonse J, Guedon J, Legrain M (1978) Focal segmental glomerulosclerosis: natural history and treatment. Nephron 21:75–81

    CAS  PubMed  Google Scholar 

  21. Cameron JS, Turner DR, Ogg CS, Chantler C, Williams DG (1978) The long-term prognosis of patients with focal segmental glomerulosclerosis. Clin Nephrol 10:213–218

    CAS  PubMed  Google Scholar 

  22. Korbet SM, Schwartz MM, Lewis EJ (1994) Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am J Kidney Dis 23:773–783

    CAS  PubMed  Google Scholar 

  23. Martinelli R, Okumura AS, Pereira LJ, Rocha H (2001) Primary focal segmental glomerulosclerosis in children: prognostic factors. Pediatr Nephrol 16:658–661

    Google Scholar 

  24. Denton MD, Magee CC, Sayegh MH (1999) Immunosuppressive strategies in transplantation. Lancet 353:1083–1091

    Article  CAS  PubMed  Google Scholar 

  25. McCauley J, Tzakis AG, Fung JJ, Todo S, Starzl TE (1990) FK 506 in steroid resistant focal sclerosing glomerulonephritis of childhood. Lancet 335:674

    Article  CAS  PubMed  Google Scholar 

  26. McCauley J, Shapiro R, Ellis D, Igdal H, TzakisA, Starzl TE (1993) Pilot trial of FK 506 in the management of steroid-resistant nephrotic syndrome. Nephrol Dial Transplant 8:1286–1290

    CAS  PubMed  Google Scholar 

  27. Schweda F, Liebl R, Riegger GAJ, Kramer BK (1997) Tacrolimus treatment for steroid- and cyclosporin-resistant minimal-change nephrotic syndrome. Nephrol Dial Transplant 12:2433–2435

    Article  CAS  PubMed  Google Scholar 

  28. Segarra A, Vila J, Pou L, Majo J, Arbos A, Quiles T, Piera L (2002) Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or –dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 17:655–662

    Article  CAS  PubMed  Google Scholar 

  29. Pennesi M, Gagliardo A, Minisini S (2003) Effective tacrolimus treatment in a child suffering from severe nephrotic syndrome. Pediatr Nephrol 18:477–478

    PubMed  Google Scholar 

  30. Hogg RJ, Portman RJ, Milliner D, Lanley KV, Eddy A, Ingelfinger J (2000) 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 105:1–16

    PubMed  Google Scholar 

  31. Anonymous (1996) Update on the 1987 Task Force Report on High-blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics 98:649–658

    PubMed  Google Scholar 

  32. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    CAS  PubMed  Google Scholar 

  33. Wildin RS, Smyk-Pearson S, Filipovich AH (2002) Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. J Med Genet 39:537–545

    Google Scholar 

  34. Budde K, Fritsche L, Neumayer H-H (1997) Differing proteinuria control with cyclosporine and tacrolimus. Lancet 349:330

    CAS  PubMed  Google Scholar 

  35. Kessler M, Champigneulles J, Hestin D, Frimat L, Renoult E (1999) A renal allograft recipient with late recurrence of focal and segmental glomerulosclerosis after switching from cyclosporine to tacrolimus. Transplantation 67:641–643

    Article  CAS  PubMed  Google Scholar 

  36. Maruyama K, Tomizawa S, Sekei Y, Arai H, Kuroume T (1992) Inhibition of vascular permeability factor production by cyclosporine in minimal change nephrotic syndrome. Nephron 62:27–30

    CAS  PubMed  Google Scholar 

  37. Maruyama K, Tomizawa S, Sekei Y, Arai J, Ogawa T, Kuroume T (1994) FK506 for vascular permeability factor production in minimal change nephrotic syndrome. Nephron 66:486–487

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine and Dentistry, University of Alberta, Alberta, Canada

    Kim Loeffler

  2. Division of Pediatric Nephrology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

    Manjula Gowrishankar & Verna Yiu

  3. Division of Pediatric Nephrology, Department of Pediatrics, 2C3 Walter MacKenzie Center, University of Alberta, Edmonton, Alberta T6G 2R7, Canada

    Verna Yiu

Authors
  1. Kim Loeffler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manjula Gowrishankar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Verna Yiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Verna Yiu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loeffler, K., Gowrishankar, M. & Yiu, V. Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 19, 281–287 (2004). https://doi.org/10.1007/s00467-003-1370-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-003-1370-3

Keywords

Search

Navigation