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

被引:5
作者
Varghese, Rini [1 ]
Majumdar, Anuradha [1 ]
机构
[1] Bombay Coll Pharm, Mumbai 400098, Maharashtra, India
关键词
Nephrotic syndrome; Glucocorticoids; Steroids; HDAC inhibitors; Proteinuria; HISTONE-DEACETYLASE INHIBITORS; REDUCES SLE PATHOGENESIS; STEROID-RESISTANT; RETINOIC ACID; SEGMENTAL GLOMERULOSCLEROSIS; MYCOPHENOLATE-MOFETIL; DIABETIC-NEPHROPATHY; RITUXIMAB TREATMENT; TRICHOSTATIN-A; RENAL INJURY;
D O I
10.1016/j.crbiot.2021.05.007
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 fibro-sis 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.
引用
收藏
页码:182 / 194
页数:13
相关论文
共 121 条
[1]   Long-Term Administration of the Histone Deacetylase Inhibitor Vorinostat Attenuates Renal Injury in Experimental Diabetes through an Endothelial Nitric Oxide Synthase-Dependent Mechanism [J].
Advani, Andrew ;
Huang, Qingling ;
Thai, Kerri ;
Advani, Suzanne L. ;
White, Kathryn E. ;
Kelly, Darren J. ;
Yuen, Darren A. ;
Connelly, Kim A. ;
Marsden, Philip A. ;
Gilbert, Richard E. .
AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (05) :2205-2214
[2]   Valproate ameliorates thioacetamide-induced fibrosis by hepatic stellate cell inactivation [J].
Aher, J. S. ;
Khan, S. ;
Jain, S. ;
Tikoo, K. ;
Jena, G. .
HUMAN & EXPERIMENTAL TOXICOLOGY, 2015, 34 (01) :44-55
[3]  
[Anonymous], 2014, PRACTICAL NEPHROLOGY
[4]  
Avner N.Y.E, 2009, PEDIATR NEPHROL, V1
[5]   Individualizing Treatment of Steroid-Resistant Nephrotic Syndrome: Registries to the Fore [J].
Bagga, Arvind ;
Sinha, Aditi .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2020, 15 (07) :920-922
[6]  
Beaudreuil S, 2017, INT J NEPHROL RENOV, V10, P97, DOI 10.2147/IJNRD.S126844
[7]   PLA2R and THSD7A: Disparate Paths to the Same Disease? [J].
Beck, Laurence H., Jr. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (09) :2580-2590
[8]   Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations [J].
Benoit, Genevieve ;
Machuca, Eduardo ;
Antignac, Corinne .
PEDIATRIC NEPHROLOGY, 2010, 25 (09) :1621-1632
[9]   Genetic syndromes caused by mutations in epigenetic genes [J].
Berdasco, Maria ;
Esteller, Manel .
HUMAN GENETICS, 2013, 132 (04) :359-383
[10]   Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management [J].
Bierzynska, Agnieszka ;
McCarthy, Hugh J. ;
Soderquest, Katrina ;
Sen, Ethan S. ;
Colby, Elizabeth ;
Ding, Wen Y. ;
Nabhan, Marwa M. ;
Kerecuk, Larissa ;
Hegde, Shivram ;
Hughes, David ;
Marks, Stephen ;
Feather, Sally ;
Jones, Caroline ;
Webb, Nicholas J. A. ;
Ognjanovic, Milos ;
Christian, Martin ;
Gilbert, Rodney D. ;
Sinha, Manish D. ;
Lord, Graham M. ;
Simpson, Michael ;
Koziell, Ania B. ;
Welsh, Gavin I. ;
Saleem, Moin A. .
KIDNEY INTERNATIONAL, 2017, 91 (04) :937-947