Matrix metalloproteinases and tissue inhibitors of metalloproteinases in chronic kidney disease and acute kidney injury: a systematic review of the literature

Abstract

Introduction: Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in remodeling the extracellular matrix. Tissue inhibitors of metalloproteinases (TIMPs) are a family of four proteins that act to limit the degradative actions of MMPs. Chronic kidney disease (CKD) and acute kidney injury (AKI) are public health problems worldwide, the prevalence of which has been increasing. Recent concept considers MMPs and TIMPs as critical factors before the onset of microalbuminuria, as well as accelerating factors associated with the breakdown of the glomerular basement membrane, renal scarring, and fibrosis during the progression of kidney diseases. Here we reviewed studies of the expression of MMPs and TIMPs in humans, using as clinical samples serum, plasma, and urine, with a focus on their potential role as molecular markers in CKD and AKI, as non-invasive markers.

Material and methods: We used as data sources, studies at Medline database using combinations of the following keywords: CKD, AKI, MMP, TIMP, serum, plasma, and urine.

Results: Evidence suggests that MMPs/TIMPs could be potential targets for therapeutic intervention in kidney diseases; future studies should attempt to improve the diagnostic or prognostic power of these families.

Discussion: Considering published guides, such as biospecimen reporting for improved study quality (BRISQ), strengthening the reporting of observational studies in epidemiology (STROBE), an updated list of essential items for reporting diagnostic accuracy studies (STARD), transparent reporting of a multivariate prediction model for individual prognosis or diagnosis (TRIPOD), and on the studies reviewed here, we have adapted published recommendations and proposed other news in order to enhance the transparency and quality of MMPs/TIMPs research in CKD and AKI. This review reinforces the complexities of MMPs/TIMPs in the pathobiology of the kidney and the need for well-designed and transparent biomedical studies. HIPPOKRATIA 2018, 22(3): 99-104.

Keywords: Matrix metalloproteinases; acute kidney injury; chronic kidney disease; tissue inhibitors of metalloproteinases.