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<p>Predicting the risks of progression to chronic kidney disease (CKD) stage 5 in idiopathic nephrotic syndrome (NS) and recurrence of the disease (rNS) following kidney transplantation (KT) is a key assessment to provide essential management information. NS has been categorized etiologically as genetic and immune-based. A genetic cause can be identified in ~ 30% of children with steroid-resistant NS (SRNS), a finding associated with a very low risk of rNS following KT. In immune-based NS, clinical overlap is observed among steroid-sensitive NS, secondary-resistant NS, and SRNS not associated with disease-causing genetic variants (non-monogenic SRNS). While ~ 50% of SRNS patients with no&#xa0;identified monogenic disease respond to intensified immunosuppressive treatments, the ones that do not&#xa0;respond to this therapy have a high risk of progression to CKD stage 5 and post-KT rNS. Secondary-resistant patients who progress to CKD stage 5 display the highest risk of post-KT rNS. The proposed shared underlying mechanism of the immune-based NS associated with post-KT rNS is based on a systemic circulating factor (CF) that affects glomerular permeability by inducing foot process effacement and focal segmental glomerulosclerosis. However, identifying patients without a detected genetic form who will recur post-KT is a major challenge. Extensive efforts, therefore, have been made to identify CFs and biomarkers potentially capable of predicting the risk of progression to CKD stage 5 and post-KT rNS. This review discusses the in vitro and in vivo approaches employed to date to identify and characterize potential CFs and CF-induced biomarkers of recurrent NS and offers an assessment of their potential to improve outcomes of KT in this patient population.</p> Graphical abstract <p></p>

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Past and future in vitro and in vivo approaches toward circulating factors and biomarkers in idiopathic nephrotic syndrome

  • 期刊论文

  • 发表日期：

    2025年1月30日

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  • Mara S. Guaragna,
  • Fernanda M. S. Casimiro,
  • Patrícia Varela,
  • Luciana de S. Feltran,
  • Andreia Watanabe,
  • Precil D. M. M. Neves,
  • João B. Pesquero,
  • Vera M. S. Belangero,
  • Paulo C. K. Nogueira,
  • Luiz F. Onuchic

摘要

Predicting the risks of progression to chronic kidney disease (CKD) stage 5 in idiopathic nephrotic syndrome (NS) and recurrence of the disease (rNS) following kidney transplantation (KT) is a key assessment to provide essential management information. NS has been categorized etiologically as genetic and immune-based. A genetic cause can be identified in ~ 30% of children with steroid-resistant NS (SRNS), a finding associated with a very low risk of rNS following KT. In immune-based NS, clinical overlap is observed among steroid-sensitive NS, secondary-resistant NS, and SRNS not associated with disease-causing genetic variants (non-monogenic SRNS). While ~ 50% of SRNS patients with no identified monogenic disease respond to intensified immunosuppressive treatments, the ones that do not respond to this therapy have a high risk of progression to CKD stage 5 and post-KT rNS. Secondary-resistant patients who progress to CKD stage 5 display the highest risk of post-KT rNS. The proposed shared underlying mechanism of the immune-based NS associated with post-KT rNS is based on a systemic circulating factor (CF) that affects glomerular permeability by inducing foot process effacement and focal segmental glomerulosclerosis. However, identifying patients without a detected genetic form who will recur post-KT is a major challenge. Extensive efforts, therefore, have been made to identify CFs and biomarkers potentially capable of predicting the risk of progression to CKD stage 5 and post-KT rNS. This review discusses the in vitro and in vivo approaches employed to date to identify and characterize potential CFs and CF-induced biomarkers of recurrent NS and offers an assessment of their potential to improve outcomes of KT in this patient population.

Graphical abstract