Urinary CD80 Discriminates Among Glomerular Disease Types and Reflects Disease Activity

Guerrico, Anatilde M. Gonzalez; Lieske, John C.; Klee, George G.; Kumar, Sanjay; López-Báez, Víctor; Wright, Adam M.; Bobart, Shane A.; Shevell, Diane E.; Maldonado, Michael A.; Troost, Jonathan P.; Hogan, Marie C.

doi:10.1016/j.ekir.2020.08.001

Cited by 15 publications

(12 citation statements)

References 42 publications

(41 reference statements)

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“…Our group recently demonstrated that CD80 is indeed present in podocytes in MCD, but, surprisingly, most CD80 was lining the capillary lumens in an endothelial pattern ( 109 ). We and others also showed that urinary CD80 levels are consistently high in a subset of patients with MCD in relapse compared to controls and to patients with other proteinuric glomerular disease ( 68 , 112 – 115 ). Interestingly, there are two cases reported in that patients with active MCD and high CD80 in urine underwent rapid transient and sustained remission following anti-CD80 therapy, respectively ( 116 , 117 ).…”

Section: Podocyte Dysfunctionsupporting

confidence: 61%

Molecular Mechanisms of Proteinuria in Minimal Change Disease

Purohit

Piani²,

Ordoñez³

et al. 2021

Front. Med.

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Minimal change disease (MCD) is the most common type of idiopathic nephrotic syndrome in childhood and represents about 15% cases in adults. It is characterized by massive proteinuria, edema, hypoalbuminemia, and podocyte foot process effacement on electron microscopy. Clinical and experimental studies have shown an association between MCD and immune dysregulation. Given the lack of inflammatory changes or immunocomplex deposits in the kidney tissue, MCD has been traditionally thought to be mediated by an unknown circulating factor(s), probably released by T cells that directly target podocytes leading to podocyte ultrastructural changes and proteinuria. Not surprisingly, research efforts have focused on the role of T cells and podocytes in the disease process. Nevertheless, the pathogenesis of the disease remains a mystery. More recently, B cells have been postulated as an important player in the disease either by activating T cells or by releasing circulating autoantibodies against podocyte targets. There are also few reports of endothelial injury in MCD, but whether glomerular endothelial cells play a role in the disease remains unexplored. Genome-wide association studies are providing insights into the genetic susceptibility to develop the disease and found a link between MCD and certain human haplotype antigen variants. Altogether, these findings emphasize the complex interplay between the immune system, glomerular cells, and the genome, raising the possibility of distinct underlying triggers and/or mechanisms of proteinuria among patients with MCD. The heterogeneity of the disease and the lack of good animal models of MCD remain major obstacles in the understanding of MCD. In this study, we will review the most relevant candidate mediators and mechanisms of proteinuria involved in MCD and the current models of MCD-like injury.

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Section: Podocyte Dysfunctionsupporting

confidence: 61%

Molecular Mechanisms of Proteinuria in Minimal Change Disease

Purohit

Piani²,

Ordoñez³

et al. 2021

Front. Med.

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“…CD80 staining in native and post-transplantation renal biopsies identified a subset of patients with FSGS in whom this mechanism seems to be relevant (74), even though these findings were not corroborated by other groups (75,76). Notably, urinary excretion of CD80 assessed in two large patient cohorts correlated with disease activity and was able to discriminate between primary and secondary FSGS forms, although the highest values were observed for MCD cases (77).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

Podestà

Ponticelli²

2020

Front. Med.

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Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.

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“…However, using multiple methodologies, we could demonstrate de novo expression of CD80 in both glomerular endothelial cells and podocytes in a subset of patients with minimal change disease (Cara-Fuentes et al, 2020). Furthermore, several other groups have also confirmed that urinary CD80 excretion increases markedly in subjects with MCD compared to other proteinuric glomerular diseases, although the clinical significance is yet to be determined (Ahmed et al, 2018;Gonzalez Guerrico et al, 2020;Ling et al, 2015Ling et al, , 2018Mishra et al, 2017). As CD80 is a coregulatory molecule in T cell response, this is consistent with evidence for immune modulation in the glomeruli in MCD (Colucci et al, 2018).…”

Section: Introductionmentioning

confidence: 64%