In Response to “Prevalence of Hypothyroidism in Children with Nephrotic Syndrome - A Systematic Review and Meta-analysis’’

Dear Editor,

We read with interest the recent report on “Prevalence of Hypothyroidism in Children with Nephrotic Syndrome - A Systematic Review and Meta-analysis” by Das et al.¹ We complement the authors for conducting a comprehensive systematic review and meta-analysis that sheds light on the significant burden of hypothyroidism in children with Nephrotic Syndrome (NS). The pooled prevalence of 41.45% is indeed noteworthy and directly impacts the development of clinical monitoring guidelines. However, some methodological issues warrant clarification to improve interpretation. First, the exceptionally high statistical heterogeneity (I2=89.23%) highlights considerable variability among primary studies.² Although the use of a random-effects model was appropriate, it may not solve the problem completely. A more detailed stratified analysis based on the assay methodology, disease activity (relapses or remission), type of NS (e.g., steroid-sensitive or steroid-resistant), regional iodine sufficiency, or concomitant medications could potentially reduce residual heterogeneity. Second, although Egger’s test disclosed the existence of publication bias despite the visually symmetrical funnel plot, no further exploration was undertaken. We recommend performing a sensitivity analysis using the trim-and-fill method to provide a statistically adjusted prevalence estimate and strengthen confidence in the overall findings.³ Additionally, the review did not assess the certainty of evidence using a standardized approach such as GRADE, which limits the ability to evaluate the confidence in the pooled estimates. Finally, given the high heterogeneity, we suggest clarifying diagnostic practices.⁴ As thyroid-stimulating hormone (TSH) cut-offs are age-dependent and the diagnostic criteria for hypothyroidism varied substantially across the 19 primary studies, publishing a supplementary table explicitly summarizing the precise TSH and Free T4 (FT4) cut-offs used would allow clinicians to accurately assess how the reported prevalence applies to their specific age-based cohorts. We appreciate the authors’ valuable work in this under-recognized area of pediatric nephrology.