Corticosteroid therapy for nephrotic syndrome in children

BACKGROUND: In nephrotic syndrome, protein leaks from the blood into the urine through the glomeruli, resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%; however, corticosteroids have well-recognised potentially serious adverse events such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, cataracts, glaucoma and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, 2015 and 2020. OBJECTIVES: The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children: 1) children in their initial episode of SSNS and 2) children who experience a relapsing course of SSNS. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 July 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) performed in children (one to 18 years) during their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent. DATA COLLECTION AND ANALYSIS: Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: = 0%). A fifth study (117 children) reported little or no difference between two weeks and four weeks of alternate-day prednisone after remission with daily prednisone. A recent large, well-designed study with 271 children found that administering daily prednisone compared with alternate-day prednisone or no prednisone during viral infection did not reduce the risk of relapse. In contrast, four previous small studies in children with frequently relapsing disease had reported that daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse. AUTHORS' CONCLUSIONS: There are four well-designed studies randomising 823 children, which have demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in efficacy using lower induction doses or shorter durations of prednisone therapy. Large, well-designed studies are required to confirm these findings. While previous small studies had suggested that changing from alternate-day to daily prednisone therapy at the onset of infection reduced the likelihood of relapse, a much larger and well-designed study found no reduction in the number relapsing when administering daily prednisone at the onset of infection.

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