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New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

Pediatric Nephrology volume 26, pages 881–892 (2011)Cite this article

Abstract

Although many children with idiopathic nephrotic syndrome (INS) respond initially to steroid therapy, repeated courses for patients with relapses often cause significant steroid toxicity. Patients with frequent relapses who develop steroid dependency thus require alternative treatment. The first such options have been considered to be cyclophosphamide or levamisole, although the latter is no longer available in many countries. There is also an increasing body of data indicating that mycophenolic acid (MPA) may be an alternative for these patients. Calcineurin inhibitors (cyclosporine A or tacrolimus) are usually effective and often used after cytotoxic treatment, but long-term treatment with these agents is necessary, raising concerns of a possible accumulation of side effects. Some patients show a tendency to relapse even on such maintenance regimens, and some even have a refractory course that creates a medical dilemma. For this situation, recent data indicate that monoclonal antibodies directed to B-cells (e.g. rituximab) may have some effect and that such drugs may also prove to be a therapeutic option in less complicated cases. Patients that do not respond to steroid treatment need genetic testing and a renal biopsy since focal segmental glomerulosclerosis (FSGS) may be present. Treatment options include pulse methylprednisolone, often in addition to calcineurin inhibitors, mainly in the form of cyclosporine, but tacrolimus has also come into recent favor. Some studies have found cytotoxic treatment, especially intravenous cyclophosphamide, to be effective in steroid resistant nephrotic syndrome, but it seems to be inferior to calcineurin inhibitors. MPA and rituximab have also been used in children with primary FSGS, but the response seems to be inferior to that in patients with steroid sensitive nephrotic syndrome. Taken together, INS in both steroid-sensitive and steroid-resistant patients is a potentially complicated disorder, and despite a wide arsenal of immunological interventions, some patients have a treatment refractory course. Prospective studies or at least standardized treatment for complicated cases is urgently needed.

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Authors and Affiliations

  1. Pediatric Nephrology, University Medical Center Hamburg–Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Michael van Husen & Markus J. Kemper

Authors
  1. Michael van Husen
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  2. Markus J. Kemper
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Correspondence to Markus J. Kemper.

Additional information

Questions

Answers appear following the reference list.

Each statement is either correct or false.

1. The idiopathic nephrotic syndrome

(a) is rarely associated with response to steroids

(b) always responds to steroid treatment

(c) the majority of patients with minimal change disease respond to steroids

(d) pulse methylprednisolone is now used in many instances for children with steroid resistance

(e) clinical definitions are identical world-wide

2. Children with steroid resistant nephrotic syndrome

(a) should receive a kidney biopsy

(b) should be investigated for podocin mutations

(c) should be treated with cyclophosphamide initially

(d) have a low risk of end-stage renal disease, even if unresponsive to treatment

(e) are at risk of recurrence after renal transplantation

3. According to recent data, the rate of long-term remission after a 12-week course of cyclophosphamide in steroid sensitive nephrotic syndrome is

(a) Approx. 80–100%

(b) Approx. 70–80%

(c) Approx. 50–60%

(d) Approx. 45–55%

(e) Approx. 25–35%

4. Calcineurin inhibitors

(a) are effective drugs in severe steroid dependency

(b) seem to be superior as first choice in steroid resistant nephrotic syndrome compared to cytotoxic treatment

(c) may cause nephrotoxicity

(d) lead to long-term remission in steroid sensitive nephrotic syndrome even when treatment is discontinued

(e) have similar cosmetic side effects

5. Rituximab is currently used in individual patients with the idiopathic nephrotic syndrome (SSNS and SRNS). Rituximab

(a) depletes B- and T-cells

(b) does not have any documented side effects

(c) response is better in SSNS than in SRNS

(d) should be administered 4 times initially in all patients, as shown by randomized studies

(e) has been used also for patients with recurrence of FSGS after renal transplantation

6. The treatment of steroid-sensitive nephrotic syndrome with mycophenolic acid (MPA)

(a) may lead to a steroid-sparing effect

(b) has been evaluated in randomized controlled studies

(c) carries the risk of nephrotoxicity

(d) typical side effects include diarrhea

(e) the role of therapeutic drug monitoring in nephrotic syndrome remains to be established

Answers

1.

(a) false

(b) false

(c) correct

(d) correct

(e) false

2.

(a) correct

(b) correct

(c) false

(d) false

(e) correct

3.

(a) false

(b) false

(c) false

(d) false

(e) correct

4.

(a) correct

(b) correct

(c) correct

(d) false

(e) false

5.

(a) false

(b) false

(c) correct

(d) false

(e) correct

6.

(a) correct

(b) false

(c) false

(d) correct

(e) correct

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van Husen, M., Kemper, M.J. New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26, 881–892 (2011). https://doi.org/10.1007/s00467-010-1717-5

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  • DOI: https://doi.org/10.1007/s00467-010-1717-5

Keywords

  • Nephrotic syndrome
  • Steroid sensitive
  • Steroid resistant
  • Immunosuppression
  • Minimal change glomerulonephritis
  • Focal segmental glomerulosclerosis