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

Abstract

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.

Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis

“…As previously discussed, this pathogenic mechanism is also applicable to all forms of INS, including those with characteristics of MCD on kidney biopsy ( 6 , 79 , 104 ). As a result, some authors refer to these conditions as a single “circulating factor disease” ( 105 – 107 ).…”