The inclusion criteria consist of children under 18 years old with NS, defined as patients with gross proteinuria (+ +  + or more) with UPcr > 200 mg/mmol, hypoalbuminemia (albumin < 2.5 g/dl), and edema. Exclusion criteria include participants older than 18 years old.

Eligible interventions included once-daily steroid regimens. The comparison group consisted of patients who received divided (multiple daily) steroid doses. Only studies that directly compared single-dose versus multiple-dose steroid regimens were included.

Studies were included if they reported at least one of our predefined outcomes of interest. Our primary efficacy outcomes were: (1) time to remission, measured in days from the start of prednisolone therapy, and (2) relapse-related outcomes, including relapse frequency during follow-up, whether a relapse occurred, and, when available, the time to first relapse. Secondary outcomes included adverse events and HPA-axis suppression. Adverse events encompassed infections, Cushingoid features, behavioral changes, gastrointestinal symptoms, serious infections, obesity, and skin infections such as impetigo, as described by each individual trial. Objective assessment of HPA-axis suppression was available in only one study. Although growth parameters (including height) were part of our prespecified outcomes, none of the included studies reported longitudinal growth data, and therefore, these outcomes could not be evaluated.

This systematic review and meta-analysis includes studies published from the inception of the database, restricted to those available in English and Spanish. Eligible study designs include randomized clinical trials (RCTs), crossover studies, and non-randomized comparatives studies. Excluded studies consist of reviews, protocol articles, books, conference abstracts, editorials, letters to editor, news articles, or other non-original research. Additionally, studies were excluded if they are duplicates, lack methodological detail, or if the necessary data could not be obtained after attempts to contact the original authors.

A systematic search was initially conducted on July 9, 2025, on PubMed MEDLINE, Cochrane, Scopus, Web of Science, EMBASE, CINAHL, and Google Scholar using the following terms: “nephrotic syndrome”, “pediatrics”, “single dose steroid”, “multiple-dose steroid”.

All references were exported to Rayyan (Rayyan Systems Inc., Cambridge, MA, USA), and duplicates were removed [10]. Two authors independently completed the eligibility assessment, first by title and abstract analysis and, subsequently, by full-text assessment. In disagreements between reviewers, a third reviewer helped reach a consensus.

The methodological quality of the included studies was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool for randomized controlled trials and the ROBINS-I tool for the non-randomized studies. Each study was evaluated across five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selective reporting. Risk of bias was categorized as low, some concerns, or high. Two independent reviewers evaluated the risk of bias in each study, considering the specific criteria and guidelines provided by the respective tools. Any reviewer discrepancies were resolved through discussion with a third blinded reviewer [11, 12].

Two independent reviewers extracted the data; disagreements were resolved by consensus. When multiple overlapping reports from the same study were identified, the information from the one containing the most relevant information or the first published report was included. Extracted data included first author, publication year, country, study design, participants’ age, sample sizes, intervention types (single vs. multiple dose), and measured outcomes. Conventional methods were used for data extraction, complemented by specialized tools such as WebPlotDigitizer (Automeris, Austin, TX, USA) for digitizing data from graphs, Cochrane Calculator for statistical conversions, and StatsToDo for advanced calculations. Additional extracted data included subgroup characteristics, such as country of study, risk of bias levels, intervention dose, and frequency [13,14,15].

A meta-analysis was performed using R version 3.4.3 (R Core Team) [16]. The pooled effect of the outcomes was examined using a random-effects meta-analysis (DerSimonian-Laird approach) [17]. Whenever the number of studies reporting an outcome of interest was insufficient, only a qualitative analysis of the results was performed. Effect sizes were expressed as relative risk (RR) or standardized mean difference (SMD) with a 95% confidence interval. The I2 statistic assessed heterogeneity, and the following cut-off values were used for interpretation: < 25, 25–50, and > 50% were considered small, medium, and large heterogeneity, respectively. For all outcomes, sensitivity analyses using the leave-one-out method were performed to determine the influence of individual studies on the overall effect. Egger's regression test was used to examine publication bias when 10 or more reports with the same outcomes were available. Whenever possible, subgroup analyses were performed for primary outcomes. Because only four eligible trials were identified, separate quantitative analyses for first episode versus relapse settings were not feasible. Therefore, we pooled all trials using time to remission as a common outcome while acknowledging the clinical heterogeneity this approach introduces.