Jun Shoji1, Akiko Mii2, Mika Terasaki3, Akira Shimizu4. 1. Division of Transplant Nephrology, University of California San Francisco, San Francisco, California, USA. 2. Department of Nephrology, Nippon Medical School, Tokyo, Japan. 3. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. 4. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan, ashimizu@nms.ac.jp.
Abstract
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD within 10-20 years. SUMMARY: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD within 10-20 years. SUMMARY: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.
Authors: Pragyi Shrestha; Kirankumar Katta; Ditmer Talsma; Annamaria Naggi; Jan-Luuk Hillebrands; Bart van de Sluis; Jacob van den Born Journal: Front Cell Dev Biol Date: 2022-03-07
Authors: Jitske Jansen; Bartholomeus T van den Berge; Martijn van den Broek; Rutger J Maas; Deniz Daviran; Brigith Willemsen; Rona Roverts; Marit van der Kruit; Christoph Kuppe; Katharina C Reimer; Gianluca Di Giovanni; Fieke Mooren; Quincy Nlandu; Helmer Mudde; Roy Wetzels; Dirk den Braanker; Naomi Parr; James S Nagai; Vedran Drenic; Ivan G Costa; Eric Steenbergen; Tom Nijenhuis; Henry Dijkman; Nicole Endlich; Nicole C A J van de Kar; Rebekka K Schneider; Jack F M Wetzels; Anat Akiva; Johan van der Vlag; Rafael Kramann; Michiel F Schreuder; Bart Smeets Journal: Development Date: 2022-05-06 Impact factor: 6.862