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