harnessing lymphocyte-cytokine networks to disrupt current paradigms in childhood nephrotic syndrome management: a systematic evidence synthesis

Background and objectives: pediatric nephrotic syndrome (ns) is characterized by immune dysregulation, with steroid resistance posing a significant therapeutic challenge. this systematic review examines the cytokine and lymphocyte profile in ns to support novel immunotherapies.method: following preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines, we searched pubmed, scopus, and web of science (2014-2024) for studies on laboratory-measured serum immune mediators in children (<15 years old) with ns after undergoing steroid treatment. studies that reported genetic polymorphisms were excluded from the review. data regarding cytokines, lymphocytes, and immunoglobulins were reviewed and synthesized from 18 human studies.results and limitations:  there were elevated levels of pro-inflammatory cytokines (il-1β, il-2, il-5, il-6, il-7, il-8, il-17a, il-18, il-23, tnf-α, ifn-γ) in active ns compared to the down-regulated anti-inflammatory cytokine, il-10, and regulatory t cells (treg). the th17/treg imbalance was prominent in the pathology of ns and a distinguishing feature of steroid-resistant nephrotic syndrome (srns). results on il-4 and il-13 showed differing patterns. limitations of this review are the human study focus which may exclude a more multifactorial cytokine network.conclusion: targeting the th17/treg axis and pro-inflammatory cytokines in ns may represent a feasible adjunct or alternative to steroids, especially in srns, and would benefit from further clinical trials.