What is circulating factor disease and how is it currently explained?

Pediatr Nephrol. 2023 Nov;38(11):3513-3518. doi: 10.1007/s00467-023-05928-8. Epub 2023 Mar 23.


Nephrotic syndrome (NS) consists of the clinical triad of hypoalbuminaemia, high levels of proteinuria and oedema, and describes a heterogeneous group of disease processes with different underlying drivers. The existence of circulating factor disease (CFD) as a driver of NS has been epitomised by a subset of patients who exhibit disease recurrence after transplantation, alongside laboratory work. Several circulating factors have been proposed and studied, broadly grouped into protease components such as soluble urokinase-type plasminogen activator (suPAR), hemopexin (Hx) and calcium/calmodulin-serine protease kinase (CASK), and other circulating proteases, and immune components such as TNF-α, CD40 and cardiotrophin-like cytokine-1 (CLC-1). While currently there is no definitive way of assessing risk of CFD pre-transplantation, promising work is emerging through the study of 'multi-omic' bioinformatic data from large national cohorts and biobanks.

Keywords: Circulating factor disease; Nephrotic syndrome; Steroid sensitive nephrotic syndrome; Steroid-resistant nephrotic syndrome; Transplant recurrence.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Nephrotic Syndrome*
  • Proteinuria
  • Receptors, Urokinase Plasminogen Activator


  • Receptors, Urokinase Plasminogen Activator