HDAC inhibitors in experimental liver and kidney fibrosis

Both chronic kidney and chronic liver diseases have high unmet medical needs, which progressively strain health budgets worldwide. The chronic nature of both conditions and the need for long term therapy are the basis for this global burden on the healthcare systems. In addition, chronic liver disease (CLD) and chronic kidney disease (CKD) are considered as disorders with high mortality. It is estimated that annually >100,000 new patients are diagnosed with CLD in the United States, contributing to the increasing number of patients who need organ replacement therapy [1]. Furthermore, about 40% of patients on a waiting list do not receive a liver transplant due to donor shortage. A recent EASL report states that approximately 29 million EU inhabitants are affected by some degree of progressive liver disease, which equals to 6% of the population [2-5]. The mortality rate for CKD and diseases of the urinary tract is about 850,000 deaths every year, which ranks CKD, like CLD, in the top 15 of high mortality disorders. Moreover, CKD is associated with an 8- to 10-fold increase in cardiovascular mortality and is a risk multiplier in patients with diabetes and hypertension. Although more common in developing countries, disadvantaged and minority populations, at least 8% of the population of Europe currently has some degree of CKD, which means that roughly 40 million people are affected in the EU. This figure increases each year and if the present trend endures, the number of people with CKD will double over the next decade [6-10].Tissue damage triggers both inflammatory and repair responses that in the case of repeated or chronic injury results in fibrosis. In organ or tissue fibrosis, the equilibrium of extracellular matrix (ECM) formation and degradation is impaired, resulting in excessive deposition of ECM by an eminent population of myofibroblasts [11]. This dysregulated biosynthetic process, leading to the accumulation of ECM, can be due to damage from ischemia, chemi