Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children

Centre for Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 10/2013; 10(10):CD002290. DOI: 10.1002/14651858.CD002290.pub4
Source: PubMed


Children with nephrotic syndrome lose excessive amounts of protein from their bloodstream into their urine, causing swelling, especially in the face, stomach and legs. The risk of infection also increases because important proteins used by children's immune systems have been lost. Corticosteroid drugs, such as prednisone, can stop protein loss, but often happens again (relapse). Giving children further corticosteroids can lead to poor growth, cataracts, osteoporosis and high blood pressure. To find out if there was evidence about non-corticosteroid drugs for children with nephrotic syndrome, and to assess what the benefits and harms of these drugs were, we analysed 32 studies that enrolled 1443 children. The studies compared several drugs and found that cyclophosphamide, chlorambucil, cyclosporin, levamisole and rituximab reduced the risk of relapse in children with frequently relapsing steroid-sensitive nephrotic syndrome. We found that more studies are needed that compare different drug treatments to determine how these medicines should be used in children with nephrotic syndrome.

Download full-text


Available from: Elisabeth M Hodson, May 07, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.
    Pediatric Nephrology 09/2014; 30(7). DOI:10.1007/s00467-014-2897-1 · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: To investigate the long-term outcome in children with frequently relapsing nephrotic syndrome (FRNS) we conducted a follow-up of a previous randomized controlled trial (RCT) 10 years after the initiation of the treatment protocol. Methods: We previously conducted an RCT on the efficacy of cyclosporine for treating children with FRNS. After 2 years of treatment, a recommended a management protocol of steroids, and immunosuppressants was provided. Results: Valid information was available for 46 of the 56 patients (82.1 %) enrolled in the original RCT. The median follow-up period was 10.3 years from the start of protocol treatment with cyclosporine. At last follow-up (mean age 18.7 years), only ten patients (21.7 %) showed disease-free remission (no relapse for at least 2 years). In contrast, 23 (50.0 %) continued to relapse frequently or were on immunosuppressants, eight patients (17.4 %) had infrequent relapses without immunosuppressants. Adverse effects attributable to treatment included short stature (6 patients), osteoporosis (six patients), obesity (4 patients), cataracts (3 patients) and hypertension (3 patients). No lethal event or renal dysfunction occurred during follow-up. Conclusions: This 10-year follow-up study shows that most children with FRNS experience relapses after 2 years of cyclosporine treatment, in adolescence and into adulthood. Outcomes in terms of life expectancy and renal function are favorable.
    Pediatric Nephrology 10/2014; 30(3). DOI:10.1007/s00467-014-2955-8 · 2.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
    Statistics in Medicine 10/2014; 33(24). DOI:10.1002/sim.6225 · 1.83 Impact Factor
Show more