Ameliorative effects of pirfenidone in chronic kidney disease
Renal fibrosis is the hallmark of advanced chronic kidney disease (CKD), which is characterized by excessive accumulation of extracellular matrix (ECM) proteins and plays a central role in the pathogenesis and progression of CKD to end-stage renal disease (ESRD). The molecular and cellular substance...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Society of Diabetic Nephropathy Prevention
2022-07-01
|
| Series: | Journal of Nephropharmacology |
| Subjects: | |
| Online Access: | https://jnephropharmacology.com/PDF/npj-11-e10458.pdf |
| _version_ | 1828139840541032448 |
|---|---|
| author | Samad Ghodrati Yeganeh Ragati Haghi Jyoti Baharani Akshaya Joseph Niloufar Alimohammadi Farzad Koosha Leila Mostafavi Aiyoub Pezeshgi |
| author_facet | Samad Ghodrati Yeganeh Ragati Haghi Jyoti Baharani Akshaya Joseph Niloufar Alimohammadi Farzad Koosha Leila Mostafavi Aiyoub Pezeshgi |
| author_sort | Samad Ghodrati |
| collection | DOAJ |
| description | Renal fibrosis is the hallmark of advanced chronic kidney disease (CKD), which is characterized by excessive accumulation of extracellular matrix (ECM) proteins and plays a central role in the pathogenesis and progression of CKD to end-stage renal disease (ESRD). The molecular and cellular substances of kidney fibrosis include growth factors, such as fibroblast growth factor (FGF), transforming growth factor beta (TGF-β) and platelet-derived growth factor (PDGF), alongside cytokines (like interleukin-1b) and metalloproteinases. Therefore, these factors can be evaluated as possible targets for anti-fibrotic agents. Among the mediators of fibrosis, TGF-β is the dominant facilitator of renal fibrosis that induces ECM construction and accumulation. Numerous studies have focused on the inhibition of TGF-β and its downstream targets for the treatment of renal disease. Abolition of TGF-β mRNA expression was found to be the mechanism of anti-fibrotic drug, pirfenidone, in the heart and kidneys of diabetic rats. Various investigations have shown the impact of pirfenidone in diminishing kidney fibrosis, with studies containing patients diagnosed with subtotal nephrectomy, diabetic kidney disease and unilateral ureteral obstruction (UUO), administered drugs such as cyclosporine, tacrolimus, doxorubicin and vanadate. Several therapeutic drugs for fibrosis reduce only one of the oxidative, inflammatory or profibrogenic markers, while pirfenidone targets all three of these markers and therefore, seems to be a particularly valuable drug. |
| first_indexed | 2024-04-11T18:58:57Z |
| format | Article |
| id | doaj.art-d10cfe21d5574e8d9aba0abf388abb58 |
| institution | Directory Open Access Journal |
| issn | 2345-4202 |
| language | English |
| last_indexed | 2024-04-11T18:58:57Z |
| publishDate | 2022-07-01 |
| publisher | Society of Diabetic Nephropathy Prevention |
| record_format | Article |
| series | Journal of Nephropharmacology |
| spelling | doaj.art-d10cfe21d5574e8d9aba0abf388abb582022-12-22T04:08:06ZengSociety of Diabetic Nephropathy PreventionJournal of Nephropharmacology2345-42022022-07-01112e10458e1045810.34172/npj.2022.10458npj-10458Ameliorative effects of pirfenidone in chronic kidney diseaseSamad Ghodrati0Yeganeh Ragati Haghi1Jyoti Baharani2Akshaya Joseph3Niloufar Alimohammadi4Farzad Koosha5Leila Mostafavi6Aiyoub Pezeshgi7Zanjan Metabolic Disease Research Center, Zanjan University of Medical Sciences, Zanjan, IranMassachusetts College of Pharmacy and Health Sciences - Worcester Campus: Worcester, MA, USAUniversity Hospitals Birmingham, B95SS, UKDepartment of Pharmaceutical Sciences at the University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Medicine, New York University, School of Medicine, New York, New York, USADepartment of Oral Biology and Pathology, State University of New York at Stony Brook, NY, USADepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAZanjan Metabolic Disease Research Center, Zanjan University of Medical Sciences, Zanjan, IranRenal fibrosis is the hallmark of advanced chronic kidney disease (CKD), which is characterized by excessive accumulation of extracellular matrix (ECM) proteins and plays a central role in the pathogenesis and progression of CKD to end-stage renal disease (ESRD). The molecular and cellular substances of kidney fibrosis include growth factors, such as fibroblast growth factor (FGF), transforming growth factor beta (TGF-β) and platelet-derived growth factor (PDGF), alongside cytokines (like interleukin-1b) and metalloproteinases. Therefore, these factors can be evaluated as possible targets for anti-fibrotic agents. Among the mediators of fibrosis, TGF-β is the dominant facilitator of renal fibrosis that induces ECM construction and accumulation. Numerous studies have focused on the inhibition of TGF-β and its downstream targets for the treatment of renal disease. Abolition of TGF-β mRNA expression was found to be the mechanism of anti-fibrotic drug, pirfenidone, in the heart and kidneys of diabetic rats. Various investigations have shown the impact of pirfenidone in diminishing kidney fibrosis, with studies containing patients diagnosed with subtotal nephrectomy, diabetic kidney disease and unilateral ureteral obstruction (UUO), administered drugs such as cyclosporine, tacrolimus, doxorubicin and vanadate. Several therapeutic drugs for fibrosis reduce only one of the oxidative, inflammatory or profibrogenic markers, while pirfenidone targets all three of these markers and therefore, seems to be a particularly valuable drug.https://jnephropharmacology.com/PDF/npj-11-e10458.pdfpirfenidonechronic kidney diseasetransforming growth factor betaend-stage renal disease |
| spellingShingle | Samad Ghodrati Yeganeh Ragati Haghi Jyoti Baharani Akshaya Joseph Niloufar Alimohammadi Farzad Koosha Leila Mostafavi Aiyoub Pezeshgi Ameliorative effects of pirfenidone in chronic kidney disease Journal of Nephropharmacology pirfenidone chronic kidney disease transforming growth factor beta end-stage renal disease |
| title | Ameliorative effects of pirfenidone in chronic kidney disease |
| title_full | Ameliorative effects of pirfenidone in chronic kidney disease |
| title_fullStr | Ameliorative effects of pirfenidone in chronic kidney disease |
| title_full_unstemmed | Ameliorative effects of pirfenidone in chronic kidney disease |
| title_short | Ameliorative effects of pirfenidone in chronic kidney disease |
| title_sort | ameliorative effects of pirfenidone in chronic kidney disease |
| topic | pirfenidone chronic kidney disease transforming growth factor beta end-stage renal disease |
| url | https://jnephropharmacology.com/PDF/npj-11-e10458.pdf |
| work_keys_str_mv | AT samadghodrati ameliorativeeffectsofpirfenidoneinchronickidneydisease AT yeganehragatihaghi ameliorativeeffectsofpirfenidoneinchronickidneydisease AT jyotibaharani ameliorativeeffectsofpirfenidoneinchronickidneydisease AT akshayajoseph ameliorativeeffectsofpirfenidoneinchronickidneydisease AT niloufaralimohammadi ameliorativeeffectsofpirfenidoneinchronickidneydisease AT farzadkoosha ameliorativeeffectsofpirfenidoneinchronickidneydisease AT leilamostafavi ameliorativeeffectsofpirfenidoneinchronickidneydisease AT aiyoubpezeshgi ameliorativeeffectsofpirfenidoneinchronickidneydisease |