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Title: New pharmacologic agents that target inflammation and fibrosis in non-alcoholic steatohepatitis-related kidney disease.
Epworth Authors: Cohney, Solomon (Shlomo)
Other Authors: Musso, Giovanni
De Michieli, Franco
Bongiovanni, Daria
Parente, Renato
Framarin, Luciana
Leone, Nicola
Berrutti, Mara
Gambino, Roberto
Cassader, Maurizio
Paschetta, Elena
Keywords: UroRenal, Vascular Clinical Institute, Epworth HealthCare, Victoria, Australia
Department of Nephrology, Epworth HealthCare, Richmond, Victoria, Australia.
Department of Gastroenterology, Epworth HealthCare, Richmond, Victoria, Australia.
Kidney Diseases
Anti-Inflammatory Agents
Nonalcoholic Steatohepatitis
Non-alcoholic Fatty Liver Disease
Receptor, Epidermal Growth Factor
Epidermal Growth Factor Receptor
Protein Kinases
Issue Date: 2016
Publisher: Elsevier
Citation: Clinical Gastroenterology and Hepatology. 2016 Aug 10. pii: S1542-3565(16)30511-0
Abstract: Epidemiological data set an association between the prevalence and severity of NAFLD and the incidence and stage of chronic kidney disease(CKD); furthermore, NASH-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation(SLKT) and a poorer renal outcome than cirrhosis of other etiologies even after SLKT. These data suggest NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are incompletely targeted by current treatments. We reviewed therapeutic approaches at late preclinical/early clinical stage of development in NASH and/or CKD, focusing on anti-inflammatory and anti-fibrotic treatments, which could retard progression of both disease conditions. Renin inhibitors and ACE2 activators are new renin-angiotensin axis modulators that showed incremental advantages over ACEIs/ARBs in preclinical models. Novel, potent and selective agonists of peroxisome proliferator-activated receptors and of farnesoid X receptor, designed to overcome limitations of older compounds, gave promising results in clinical trials. Epigenetics, heat stress response and common effectors of redox regulation are also subjected to intensive research, while the gut is targeted by several approaches, including synbyotics, anti-LPS antibodies, Toll-Like Receptor-4 antagonists, incretin mimetics and Fibroblast Growth Factor(FGF)19 analogs. Promising anti-inflammatory therapies include inhibitors of NLRP3 inflammasome, of NF-κB, and of Vascular Adhesion Protein(VAP)-1, chemokine antagonists, and solithrmycin, while approaches targeting common pro-fibrogenic pathways operating in the liver and the kidney include galectin-3 antagonists, and inhibitors of Rho-associated Protein Kinase and of Epidermal Growth Factor activation. The evidence, merits and limitations of each approach fot the treatment of NASH and CKD are discussed.
DOI: 10.1016/j.cgh.2016.08.002
PubMed URL:
ISSN: 1542-3565
Journal Title: Clinical Gastroenterology and Hepatology.
Type: Journal Article
Affiliated Organisations: Gradenigo Hospital, University of Turin, Turin, Italy.
Department of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
The University of Melbourne, Parkville, Victoria, Australia.
Department of Nephrology, Western Hospital, Sunshine/Footscray, Victoria, Australia.
Department of Gastroenterology, Epworth HealthCare, Richmond, Victoria, Australia.
Type of Clinical Study or Trial: Retrospective studies
Appears in Collections:UroRenal, Vascular

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