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Soluble Urokinase Receptor as a Biomarker in Kidney Disease

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Biomarkers in Kidney Disease

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Abstract

Urokinase receptor (uPAR), a glycosylphosphatidylinositol (GPI)-anchored protein, engages in multiple protein-protein interactions and various biological functions. Its soluble form, soluble uPAR (suPAR), has been linked to various diseases and conditions including focal segmental glomerulosclerosis (FSGS). It has been long speculated that a circulating permeability factor should be implicated in the pathogenesis of the disease because a substantial portion of the patients experience recurrence shortly after renal transplantation. In 2011, Reiser and colleagues suggested that suPAR might be not only a potential pathogenic permeability factor but also a diagnostic biomarker. Following this report, renal researchers worldwide have analyzed the validity of suPAR as a diagnostic biomarker for primary FSGS and posttransplant FSGS. Furthermore, the utility of suPAR as a biomarker in other renal diseases including diabetic nephropathy and immunoglobulin A (IgA) nephrosis has been also suggested.

In this chapter, a comprehensive review of suPAR as a diagnostic biomarker and as a predictive biomarker in kidney diseases is provided.

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Authors and Affiliations

  1. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan

    Takehiko Wada

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  1. Takehiko Wada
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Correspondence to Takehiko Wada .

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Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

Definitions of Words and Terms

Enzyme-linked immunosorbent assay (ELISA)

ELISA is a plate-based assay technique designed for detecting and quantifying peptides, proteins, antibodies, etc. In quantitative sandwich immunoassay technique employed in the assay for uPAR, an antibody specific for uPAR has been precoated onto a microplate. Samples and controls are pipetted into the wells, and uPAR is bound by the immobilized antibody. After washing away unbound substances, an enzyme-linked polyclonal antibody specific for uPAR is added to the wells. Following a washing process, a substrate solution is added, and the intensity of the developed color is measured.

Galactose affinity chromatography

Affinity chromatography is a separation method based on a specific interaction between an immobilized ligand and its binding partner. In search for a circulating permeability factor, Savin and colleagues postulated that the factor might have a lectin-like interaction with sugar of the podocyte glycocalyx. Therefore, they used galactose-agarose beads to isolate a substance which could interact with galactose.

Glycosylphosphatidylinositol (GPI) anchor

GPI anchor is a posttranslational modification that links modified protein in the outer leaflet of the plasma membrane.

Podocyte

The podocyte is one of the resident cells in the glomerulus. Podocytes are located at the outer aspect of capillary tuft. A podocyte is considered to be a terminally differentiated cell, and it comprises a large cell body, major processes, and foot processes. The cells play an important role in filtration barrier system.

Receiver operating characteristic (ROC) analysis

An ROC graph is a technique for visualizing, organizing, and selecting classifiers based on their performance. The curve is created by plotting the true positive rate against the false-positive rate at various threshold settings. An analysis using ROC curve (ROC analysis), which is useful to select possibly optimal models, has been extended for use in visualizing and analyzing the behavior of diagnostic systems.

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Wada, T. (2015). Soluble Urokinase Receptor as a Biomarker in Kidney Disease. In: Patel, V. (eds) Biomarkers in Kidney Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7743-9_50-1

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  • DOI: https://doi.org/10.1007/978-94-007-7743-9_50-1

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