The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?

Abstract

Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also in the development of new treatments is the lack of markers able to identify and stratify patients with stable versus progressive disease. At the moment renal biopsy is the only means of diagnosing renal interstitial fibrosis. Novel biomarkers should improve diagnosis of a disease, estimate its prognosis and assess the response to treatment, all in a non-invasive manner. Existing markers of CKD do not fully and specifically address these requirements and in particular do not specifically reflect renal fibrosis. The aim of this review is to give an insight of the involvement of the extracellular matrix (ECM) proteins in kidney diseases and as a source of potential novel biomarkers of renal fibrosis. In particular the use of the protein fingerprint technology, that identifies neo-epitopes of ECM proteins generated by proteolytic cleavage by proteases or other post-translational modifications, might identify such novel biomarkers of renal fibrosis.

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…In kidney allografts, increased urinary CCL-2 was associated with renal fibrosis (317). It should be mentioned, however, that most of the mentioned markers are not kidney specific, perhaps except FGF-23, and the true diagnostic value in CKD has not yet been established (379,392). Importantly, none of these markers is specific for interstitial fibrosis but rather reflects other processes.…”

“…Factors directly involved in fibrogenesis, ECM proteins and products of their turnover, are also attractive biomarkers of interstitial fibrosis (379). Urinary TGF-b1 and CTGF levels correlated with renal fibrosis (284,398,399).…”

Experimental Inhibition of Periostin Attenuates Kidney Fibrosis

“…Various intracellular signaling pathways are associated with kidney fibrosis, and transforming growth factor-β (TGF-β) plays a key role in modulating cell migration, inflammatory cell infiltration, and extracellular matrix (ECM) turnover [6, 7]. …”

Untitled

“…6,33 Although there are many different causative pathologies, both kidney disease and eventual graft failure are associated with inflammation and fibrosis, the latter characterized by excess connective tissue deposition. 2,34,35 Chronic injury leads to scarring with excessive myofibroblast proliferation and consequent production of ECM proteins, particularly collagens.…”