Glomerular Deposition of Nephritis-Associated Plasmin Receptor (NAPlr) and Related Plasmin Activity: Key Diagnostic Biomarkers of Bacterial Infection-related Glomerulonephritis.

Takahiro Uchida,Takashi Oda

doi:10.3390/ijms21072595

Abstract

It is widely known that glomerulonephritis (GN) often develops after the curing of an infection, a typical example of which is GN in children following streptococcal infections (poststreptococcal acute glomerulonephritis; PSAGN). On the other hand, the term “infection-related glomerulonephritis (IRGN)” has recently been proposed, because infections are usually ongoing at the time of GN onset in adult patients, particularly in older patients with comorbidities. However, there has been no specific diagnostic biomarker for IRGN, and diagnosis is based on the collection of several clinical and pathological findings and the exclusion of differential diagnoses. Nephritis-associated plasmin receptor (NAPlr) was originally isolated from the cytoplasmic fraction of group A streptococcus as a candidate nephritogenic protein for PSAGN and was found to be the same molecule as streptococcal glyceraldehyde-3-phosphate dehydrogenase and plasmin receptor. NAPlr deposition and related plasmin activity were observed with a similar distribution pattern in the glomeruli of patients with PSAGN. However, glomerular NAPlr deposition and plasmin activity could be observed not only in patients with PSAGN but also in patients with other glomerular diseases, in whom a preceding streptococcal infection was suggested. Furthermore, such glomerular staining patterns have been demonstrated in patients with IRGN induced by bacteria other than streptococci. This review discusses the recent advances in our understanding of the pathogenesis of bacterial IRGN, which is characterized by NAPlr and plasmin as key biomarkers.

Highlights

A wide variety of bacterial infection-related renal diseases are known, among which the most common is acute kidney injury (AKI) [1], which occurs as part of multiple organ failure
Glomerular Nephritis-associated plasmin receptor (NAPlr) deposition and plasmin activity have recently been demonstrated in patients with infection-related glomerulonephritis (IRGN) induced by some bacterial strains, such as Streptococcus pneumoniae [28], Aggregatibacter actinomycetemcomitans [29], Mycoplasma pneumoniae [30], or S. aureus
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from various bacteria appear to react with the anti-NAPlr antibody and to have plasmin-binding ability, and positivity of the anti-NAPlr antibody and plasmin activity in glomeruli may act as both diagnostic and pathogenetic biomarkers of bacterial IRGN in general

Summary

Introduction

A wide variety of bacterial infection-related renal diseases are known, among which the most common is acute kidney injury (AKI) [1], which occurs as part of multiple organ failure. As streptococcal infections are usually cured when GN is diagnosed and there is a distinct infection-free latent period, the GN has been referred to as poststreptococcal acute glomerulonephritis (PSAGN) [2,3,4]. Whereas PSAGN is still the most common cause of pediatric AGN, adult AGN cases have been increasing, and those associated with non-streptococcal infections, infections by Staphylococcus aureus, are as common as PSAGN [5]. In adult AGN patients, the infection is usually still present at the time when GN is diagnosed. Based on these backgrounds, instead of “postinfectious AGN”, the disease concept of infection-related glomerulonephritis (IRGN) has recently been proposed [5]. Infections of various viruses, mycobacteria, fungi, or protozoa are known to cause IRGN [1], they are not within the scope of this article

NAPlr and Plasmin Activity in Glomeruli as Biomarkers of PSAGN

NAPlr and Plasmin Activity in Extraglomerular Regions

Concluding Remarks