Current Therapies in Nephrotic Syndrome: HDAC inhibitors, an Emerging Therapy for Kidney Diseases

Abstract

• Nephrotic syndrome (NS) is one among the chronic kidney conditions occurring in children as well as in adult population. • Conventional therapies for NS include treatment with steroids, ACE inhibitors and monoclonal antibodies, with no universal treatment for the condition as yet. • HDAC inhibitors have been greatly explored in the recent past for their anti-fibrotic, anti-inflammatory and immunosuppressive effects in several tissues and organs. • Increasing evidence suggests that treatment with HDAC inhibitors can attenuate renal sclerosis, fibrosis and proteinuria associated with chronic kidney diseases. • HDAC inhibitors can be considered as an emerging therapy for treating NS however; further preclinical and clinical investigations are indispensable. Nephrotic syndrome (NS) is one amongst the foremost chronic kidney conditions occurring in children as well as in adults with a characteristic feature of podocyte injury. Currently, there is no refined treatment available for this condition and in most of the cases, the treatment is essentially experiential. Therapies for NS presently include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, monoclonal antibodies, steroids, and immunosuppresants. Steroids continue to be the initial treatment approach for NS patients and are considered as the foundation of the therapy. However, it is observed that about 50% of the patients with NS are steroid sensitive and therefore portray some response to steroids while the remainder are considered to be steroid-resistant and patients advance to end stage renal disease. As a result, the freight of morbidity becomes prodigious to patients and health services, specifically in the management of dialysis and transplantation. Although numerous studies have been done in the area of renal disorders, treatment of NS remains a critical challenge till date. This is due to the fact that the underlying mechanisms and causes are still not clearly understood. Therapies are now being refined and directed specifically to target the podocyte. In the recent past, histone deacetylase inhibitors (HDACi) have been greatly explored to treat chronic kidney diseases because of the anti-fibrotic, anti-inflammatory, and immunosuppressive effects that they exhibit. Histone deacetylases (HDACs) are the class of enzymes that remove the acetyl groups from the lysine amino acid on histone and thereby promote chromatin condensation and repression of transcription. HDACi are the chemical compounds that inhibit HDAC and alter gene transcription by inducing changes in the structure of proteins in transcription factor complexes. An irregular expression of HDACs has been noted that subsequently play a role in renal fibrosis and glomerulosclerosis associated with chronic renal conditions. Therefore, targeting HDACs can be a favourable therapeutic strategy to treat NS. In the present review, we outline the potential use of HDACi as therapeutic alternatives in treating NS. The promise of HDACi in NS is pragmatically put forth in this review.