Corticosteroid Therapy for Steroid-Sensitive Nephrotic Syndrome in Children: Dose or Duration?

Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
Journal of the American Society of Nephrology (Impact Factor: 9.34). 12/2012; 24(1). DOI: 10.1681/ASN.2012111093
Source: PubMed
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    ABSTRACT: Ethnopharmacological relevance: Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria. Podocyte injury plays a key role in proteinuria, one of the principal means for the control of NS is to prevent podocyte injury. Qi-Dan Fang consists of two of the most extensively applied herbal remedies among Traditional Chinese Medicine (TCM) (Radix Astragali Mongolici and Radix Salviae Miltiorrhizae, with a weight ratio of 5:1) which are specifically used for the treatment of various kidney diseases. In previous studies, we found that Qi-Dan Fang provides improvement to patients with adriamycin-induced nephrotic syndrome by alleviating proteinuria and serum lipid. The aim of this study is to study the efficiency of Qi-Dan Fang on NS model rat with renal dysfunction and podocyte injury, something which has not been carried out yet. Materials and methods: The rats were divided into Normal, Model, Jin Gui Shen Qi Pill (4.12 g/kg), Qi-Dan Fang (3.09, 6.17 and 12.34 g/kg/d) groups, they were each given a single tail intravenous injection of Adriamycin (6.0 mg/kg) except for the Normal group and were orally administered dosages of Qi-Dian Fang and Jin Gui Shen Qi pills once daily for 7 weeks. Following the treatment, the content of cystation C (CysC), blood urea nitrogen (BUN), serum creatinine (Scr) were measured with an autobiochemical analyser. The pathomorphological changes to the glomeruli, the mRNA expressions of nephrin, podocin, CD2AP genes and p53, bax, bcl-2 proteins expressions were also carried out to probe the effects of Qi-Dan Fang. Results: (1) Qi-Dan Fang treatment raised the level of CysC in blood serum while lowering the content of BUN and Scr in the adriamycin-induced nephrotic syndrome rat model; (2) Long-term administration of Qi-Dan Fang was able to ameliorate pathomorphological change of glomeruli and repair the organization structure of Glomerulus; (3) Qi-Dan Fang could increase the mRNA expression of nephrin, podocin and CD2AP genes, down-regulate the expression of p53, bax proteins, while increased bcl-2 protein to protect the podocyte and restore Glomerular selective filtration function. Conclusions: Results of our present studies reveal that Qi-Dan Fang is able to enhance renal function, inhibit podocyte injury to provide improvements to the Adriamycin-induced nephrotic syndrome.
    Journal of ethnopharmacology 01/2014; 151(3). DOI:10.1016/j.jep.2013.12.028 · 3.00 Impact Factor
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    ABSTRACT: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). National study, comprised of all 13 Canadian pediatric nephrology clinics. 400 patients under 18 years of age to be recruited over 2.5 years. Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.
    07/2014; 1:17. DOI:10.1186/2054-3581-1-17
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    ABSTRACT: In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome.Kidney International advance online publication, 23 July 2014; doi:10.1038/ki.2014.260.
    Kidney International 07/2014; DOI:10.1038/ki.2014.260 · 8.56 Impact Factor
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