Reply to Comments on ‘Prevalence of Hypothyroidism in Children with Nephrotic Syndrome - A Systematic Review and Meta-analysis’

Dear Editor,

We sincerely thank the authors for their interest and careful reading of our article¹ and their thoughtful and constructive comments.² We have clarified several methodological points that may aid interpretation and future research in this area.

The high degree of heterogeneity observed in our pooled analyses reflects the inherent clinical and methodological diversity of studies examining thyroid dysfunction in children with nephrotic syndrome. Differences in disease activity, treatment status, subtype classification, laboratory assays, and geographic context are well known to influence thyroid function parameters in this population. A random-effects model was therefore used to account for between-study variability. Although more detailed stratified analyses would be desirable, they were not consistently feasible because many primary studies did not report these variables with sufficient detail.

Regarding publication bias, we would like to clarify the interpretation of the Egger regression test results. Although non-zero intercept values were observed in some analyses, the associated p values were not statistically significant. We acknowledge that the results section could have been more precise on this point and clarify that the statistical evidence does not support the presence of meaningful publication bias. In the absence of such evidence, further adjustment using trim-and-fill methods was not undertaken.

We acknowledge the suggestion to assess the certainty of evidence using GRADE; however, our review focused on pooled prevalence estimates rather than intervention effects, for which the GRADE application is less standardized. Nonetheless, formal certainty assessments may enhance interpretability in future prevalence reviews. Although we reported diagnostic and biochemical details wherever available, incomplete reporting in several studies limited standardization, underscoring the need for more consistent age-based diagnostic reporting in future research.

Our findings indicate a substantial burden of thyroid dysfunction in children with nephrotic syndrome, while also reflecting the limitations and heterogeneity of the existing evidence base.