Unwinding focal segmental glomerulosclerosis [version 1; referees: 3 approved]

Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers. The ongoing research is currently focusing on understanding how these molecules and pathways can interplay and be utilized as potential diagnostic and therapeutic targets. Among these molecules, the soluble urokinase plasminogen activating receptor (suPAR) has been studied in detail, both clinically and from a basic science perspective. By now, it has emerged as the earliest and most robust marker of future CKD. Other circulating factors harming podocytes include anti-CD40 auto-antibody and possibly cardiotrophin-like cytokine factor-1. Understanding these factors will aid our efforts to ultimately cure FSGS and possibly treat a larger portion of CKD patients much more effectively.