Journal
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
Volume 29, Issue 1, Pages 4-15Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNH.0000000000000570
Keywords
alkaline phosphatase; apabetalone; bromodomain and extraterminal inhibition; chronic kidney disease; epigenetic; microRNA; vascular calcification
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Funding
- ALF grants Region Ostergotland, Sweden
- NIDDK [R01DK095668, K24-DK091419]
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Purpose of review In chronic kidney disease ( CKD), disturbance of several metabolic regulatory mechanisms cause premature ageing, accelerated cardiovascular disease (CVD), and mortality. Single-target interventions have repeatedly failed to improve the prognosis for CKD patients. Epigenetic interventions have the potential to modulate several pathogenetic processes simultaneously. Alkaline phosphatase (ALP) is a robust predictor of CVD and all-cause mortality and implicated in pathogenic processes associated with CVD in CKD. Recent findings In experimental studies, epigenetic modulation of ALP by microRNAs or bromodomain and extraterminal (BET) protein inhibition has shown promising results for the treatment of CVD and other chronic metabolic diseases. The BET inhibitor apabetalone is currently being evaluated for cardiovascular risk reduction in a phase III clinical study in high-risk CVD patients, including patients with CKD (ClinicalTrials.gov Identifier: NCT02586155). Phase II studies demonstrate an ALP-lowering potential of apabetalone, which was associated with improved cardiovascular and renal outcomes. Summary ALP is a predictor of CVD and mortality in CKD. Epigenetic modulation of ALP has the potential to affect several pathogenetic processes in CKD and thereby improve cardiovascular outcome.
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