Glomerular endothelial cells and podocytes can express CD80 in patients with minimal change disease during relapse
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ORIGINAL ARTICLE
Glomerular endothelial cells and podocytes can express CD80 in patients with minimal change disease during relapse Gabriel Cara-Fuentes 1 & Madhusudan Venkatareddy 2 & Rakesh Verma 2 & Alfons Segarra 3 & Audrey C. Cleuren 4 & Alfonso Martínez-Ramos 5 & Richard J. Johnson 6 & Puneet Garg 2 Received: 4 December 2019 / Revised: 5 March 2020 / Accepted: 18 March 2020 # IPNA 2020
Abstract Background Urinary CD80 has emerged as potential biomarker in idiopathic nephrotic syndrome (INS). However, its cellular source remains controversial. The aim of the study was to assess whether CD80 is truly expressed by glomerular cells in INS patients during relapse and in the LPS mouse model of podocyte injury. Methods The presence of CD80 in glomeruli was evaluated by combining immunostaining, immunogold labeling, and in situ hybridization techniques. Results CD80 was present along the surface of glomerular endothelial cells (GEC) and rarely in podocytes in six of nine minimal change disease (MCD) patients in relapse, two of eleven patients with focal segmental glomerulosclerosis in relapse, and absent in controls. In mice, CD80 was upregulated at mRNA and protein level in GEC and podocytes, in a similar pattern to that seen in MCD patients. Conclusions Glomerular endothelial cells and podocytes can express CD80 in patients with MCD during relapse. A better understanding of the role of CD80 in glomerular cells may provide further insights into the mechanisms of proteinuria in INS. Keywords CD80 . Biomarker . Nephrotic syndrome . Glomerular endothelial cell . Podocyte
Introduction Idiopathic nephrotic syndrome (INS) refers to a heterogeneous group of glomerular disorders, including minimal change disease
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00467-020-04541-3) contains supplementary material, which is available to authorized users. * Gabriel Cara-Fuentes [email protected] 1
Division of Pediatric Nephrology, Department of Pediatrics, University of Michigan, MSRB-2, Room 1574, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA
2
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA
3
Division of Nephrology, Hospital Vall d’Hebron, Barcelona, Spain
4
Life Sciences Institute, University of Michigan, Ann Arbor, USA
5
School of Medicine, University of Granada, Granada, Spain
6
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, USA
(MCD) and focal segmental glomerulosclerosis (FSGS), characterized by severe proteinuria and podocyte foot process effacement [1]. While MCD is usually associated with favorable steroid response and long-term outcome, FSGS often leads to progressive chronic kidney disease (CKD) and/or end-stage renal disease (ESRD) [2]. Nevertheless, the clinical and histological distinction between these entities can be challenging in early stages. Currently, there are no validated biomarkers to help with diagnosis, to predict outcomes, or to individ
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