Role of matrix metalloproteinase (MMP)-9 in chronic kidney disease: a new biomarker of resistant albuminuria

Resistant albuminuria developed under adequate chronic renin-angiotensin system (RAS) blockade is a clinical problem present in a fraction of patients with chronic kidney disease (CKD). The mechanism underlying this resistant albuminuria remain unknown. Matrix metalloproteinases (MMPs) are involved in the pathophysiology of cardiovascular and renal disease. Here we tested the role of MMPs in resistant albuminuria. We first evaluated gelatinase MMP-2 and MMP-9 activity by zymography in the Munich Wistar Frömter (MWF) rat, a model of progressive albuminuria, and subsequently in patients with resistant albuminuria. Markers of oxidative stress were observed in kidneys of MWF rats together with a significant increase in proMMP-2 and active MMP-9 forms. These changes were normalized together with reduced albuminuria in consomic MWF-8SHR rats, in which chromosome 8 of MWF was replaced with the respective chromosome from spontaneous hypertensive rats (SHR). MMP-2 and MMP-9 protein levels were similar in patients with normal and resistant albuminuria; however, high circulating levels of collagen IV, a specific biomarker of tissue collagen IV degradation, were observed in patients with resistant albuminuria. These patients showed a significant increase in gelatinase MMP-2 and MMP-9 activity, but only a significant increase in the active MMP-9 form quantified by ELISA, which significantly correlated with albuminuria degree. Although TIMP-1 expression was similar, a novel AlphaLISA&...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research