Πέμπτη, 10 Οκτωβρίου 2019

Mitigating risk of aldosterone in diabetic kidney disease
Purpose of review Diabetic kidney disease is a growing problem leading to end-stage kidney disease but also atherosclerotic cardiovascular disease and heart failure. Aldosterone is a key risk factor promoting inflammation and fibrosis causing cardio-renal failure. Current options and challenges with mitigating the risk of aldosterone are reviewed. Recent findings More aggressive renin–angiotensin–aldosterone system (RAAS) blockade can be maintained in individuals with hyperkalemia if new potassium binders are added. Aldosterone synthase inhibitors may lower aldosterone without causing hyperkalemia. Novel nonsteroidal mineralocorticoid receptor antagonists (MRA) are able to lower proteinuria and markers of heart failure, with limited potassium problems and without renal impairment. Ongoing clinical trials are evaluating the safety and potential benefits of nonsteroidal MRAs on progression of renal disease and development of cardiovascular outcomes in type 2 diabetes and kidney disease. Summary Aldosterone is an important driver of inflammation and fibrosis leading to renal and cardiovascular complications. MRA lower albuminuria but data showing prevention of end-stage kidney disease are lacking. Side effects including hyperkalemia have previously prevented long-term studies in diabetic kidney disease but new treatment strategies with potassium binders, aldosterone synthase inhibitors and nonsteroidal MRA have been developed for clinical testing. Correspondence to Peter Rossing, MD, DMSc, Head of Complications Research, Steno Diabetes Center Copenhagen (SDCC), Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. Tel: +45 30 91 33 83; e-mail: Peter.Rossing@RegionH.dk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Promoting resolution in kidney disease: are we nearly there yet?
Purpose of review Nephrology lacks effective therapeutics for many of the presentations and diseases seen in clinical practice. In recent decades, we have come to understand the central place of inflammation in initiating and propagating kidney disease, and, research in more recent years has established that the resolution of inflammation is a highly regulated and active process. With this, has evolved an appreciation that this aspect of the host inflammatory response is defective in kidney disease and led to consideration of a therapeutic paradigm aiming to harness the activity of the molecular drivers of the resolution phase of inflammation. Fatty-acid-derived Specialized pro-resolving mediators (SPMs), partly responsible for resolution of inflammation have gained traction as potential therapeutics. Recent findings We describe our current understanding of SPMs for this purpose in acute and chronic kidney disease. These studies cement the place of inflammation and its defective resolution in the pathogenesis of kidney disease, and highlight new avenues for therapy. Summary Targeting resolution of inflammation is a viable approach to treating kidney disease. We optimistically look forward to translating these experimental advances into tractable therapeutics to treat kidney disease. Correspondence to Eoin Brennan, UCD Diabetes Complications Research Centre, UCD Conway Institute of Biomolecular & Biomedical Research, UCD School of Medicine, University College Dublin, Dublin 4, Ireland. E-mail: eoin.brennan@ucd.ie Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Nuclear factor erythroid 2-related factor 2 as a treatment target of kidney diseases
Purpose of review Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor which regulates a wider range of downstream pathways than previously thought. This review focuses on the novel findings about the internal regulatory mechanisms of Nrf2, the expanding understanding of its role in maintaining cellular homeostasis and the attempts to broaden the clinical application of its activators. Recent findings Nrf2 is in charge of the maintenance of cellular homeostasis under stress and there exist the internal regulatory mechanisms for Nrf2 which have recently been elucidated. New downstream pathways of Nrf2 have been discovered, including the defense against ferroptosis, the latest concept of cell death. Several Nrf2 activators are at various stages of clinical development and are being tested in clinical trials for chronic kidney disease (CKD) including diabetic kidney disease, Alport syndrome, autosomal dominant polycystic kidney disease and focal segmental glomerulosclerosis. Summary Nrf2 has been gathering attention as an emerging treatment target of chronic diseases which have oxidative stress and inflammation as their pathogenesis including CKD. Basic and clinical studies are under way to establish its role as a target for treatment of those diseases. Correspondence to Masaomi Nangaku, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel: +81 3 5800 9736; fax: +81 3 5800 9807; e-mail: mnangaku-tky@umin.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Exploring old concepts and new paradigms
No abstract available

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