*4.2. Biomarkers of Tissue Remodeling*

In addition to proteinuria and eGFR, other promising predictive biomarkers in CKD were described. A change in serum levels of MMPs after exposure to BB-1101, a synthetic hydroxamic acid-based inhibitor of MMP, was associated with a reduction in proteinuria in experimental models of glomerular damage [102]. A similar effect was observed in diabetic CKD patients who underwent treatment with doxycycline, an antibiotic from the tetracycline family, and who were already treated with renin–angiotensin–aldosterone inhibitors (RAAS-i) [103]. Moreover, MMPs are also involved in the mechanism that leads to CV risk reduction exerted by sodium–glucose cotransporter 2 inhibitors (SGLT2-i) through the activation of RECK (reversion-inducing cysteine-rich protein with kazal motifs), an endogenous inhibitor of MMPs [104]. That mechanism appeared to be independent of proteinuria levels and could also be useful for selecting high-risk normoalbuminuric CKD patients to be enrolled in future clinical trials, who represent a non-trivial proportion of the CKD cohort [21].
