EDITORIAL URRENT C OPINION
Novel therapeutics in hypertension and kidney disease C. John Sperati a and Adam Whaley-Connell b,c
In this issue of current opinion, we have focused on two broad, important concepts emerging in the pharmacology and therapeutics of hypertension and kidney disease. First is the unique intersection of the gastrointestinal system with renal physiology; specifically, the targeting of gut flora and gastrointestinal electrolyte transport. The role of the gut in salt-sensitivity and blood pressure regulation has been understudied for decades. New compounds targeting the gastrorenal axis could emerge as useful options in the management of hypertension, especially in patients with chronic kidney disease. Second is a focus on novel nonsteroidal mineralocorticoid receptor antagonists and redox stress. The advent of these new antagonists is a potentially important advance in the field for management of resistant hypertension, while hopefully mitigating the usual risk for hyperkalemia. Furthermore, antagonizing the mineralocorticoid receptor is an important strategy in reducing redoximbalance and oxidant stress in cardiovascular and kidney disease. These two broad areas of scientific discovery have been an area of active research interest in pharmacology during the past decade and, in recent years, therapeutic agents have moved into clinical trials. The search for extrarenal pathways in salt-sensitive hypertension has led to significant investigation into the renin–angiotensin–aldosterone system, the sympathetic nervous system, and the endothelin system. More recently, there has been increasing interest in the gastrorenal axis and specifically in gastrointestinal sodium transport. In the report from Jose and Raj (pp. 403–409), the authors explore the interplay of the gut microbiome with sodium transport and blood pressure regulation within the context of genetic and epigenetic regulation. This highlights mechanisms of obesity-associated hypertension [1] and the contribution of overnutrition to gastrointestinal regulation of sodium transport. These themes are continued by Spencer and Greasley (pp. 410–416) in a review of agents targeting the gut sodium– hydrogen exchanger to reduce gastrointestinal sodium absorption. These therapeutics may have
significant implications for managing salt-sensitive hypertension and volume overload in patients with kidney, hepatic, and/or cardiovascular disease. The authors present a state-of-the-art discussion on these compounds and where they stand in development. To continue, a useful strategy in the management of resistant hypertension is antagonism of the mineralocorticoid receptor. This strategy, however, has been limited by the attendant risk for hyperkalemia in patients with chronic kidney disease. The recent development of nonsteroidal antagonists may attenuate some of this risk and represents a critical advancement in the field. Kolkhof et al. (pp. 417–424) present a thorough discussion of two compounds in development and one ready for market. Inappropriate activation of the renin–angiotensin–aldosterone system and oxidant stress contribute significantly to the risk for cardiovascular and kidney disease. Despite decades of work targeting oxidant stress, a clinically useful compound has yet to be approved by the Food and Drug Administration. In this issue, Montezano et al. (pp. 425–433) explore the emerging role of Nox5 in cardiovascular tissue, the importance of Nox5 as a target in hypertension, and limitations in the study of prior antioxidant compounds. In total, this issue of Pharmacology and Therapeutics will help the reader understand two emerging areas – the gastrorenal axis and mineralocorticoid receptor antagonism/redox modulation – of drug a Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, bResearch Service, Harry S. Truman Memorial Veterans Hospital and cDivisions of Nephrology and Hypertension and Endocrinology and Metabolism, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA
Correspondence to Adam Whaley-Connell, DO, MSPH, Associate Chief of Staff for Research and Development, Harry S. Truman Memorial Veterans Hospital, Associate Professor of Medicine, University of Missouri-Columbia School of Medicine, 800 Hospital Dr, Columbia, MO 65201, USA. E-mail: [email protected] Curr Opin Nephrol Hypertens 2015, 24:401–402 DOI:10.1097/MNH.0000000000000156
1062-4821 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-nephrolhypertens.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pharmacology and therapeutics
development in the management of hypertension, particularly in those with chronic kidney disease.
Conflicts of interest There are no conflicts of interest.
Acknowledgements None.
REFERENCE
Financial support and sponsorship None.
402
www.co-nephrolhypertens.com
1.
Jindal A, Brietzke S, Sowers JR. Obesity and the cardiorenal metabolic syndrome: therapeutic modalities and their efficacy in improving cardiovascular and renal risk factors. Cardiorenal Med 2012; 2:314–327.
Volume 24 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Novel therapeutics in hypertension and kidney disease C. John Sperati a and Adam Whaley-Connell b,c
In this issue of current opinion, we have focused on two broad, important concepts emerging in the pharmacology and therapeutics of hypertension and kidney disease. First is the unique intersection of the gastrointestinal system with renal physiology; specifically, the targeting of gut flora and gastrointestinal electrolyte transport. The role of the gut in salt-sensitivity and blood pressure regulation has been understudied for decades. New compounds targeting the gastrorenal axis could emerge as useful options in the management of hypertension, especially in patients with chronic kidney disease. Second is a focus on novel nonsteroidal mineralocorticoid receptor antagonists and redox stress. The advent of these new antagonists is a potentially important advance in the field for management of resistant hypertension, while hopefully mitigating the usual risk for hyperkalemia. Furthermore, antagonizing the mineralocorticoid receptor is an important strategy in reducing redoximbalance and oxidant stress in cardiovascular and kidney disease. These two broad areas of scientific discovery have been an area of active research interest in pharmacology during the past decade and, in recent years, therapeutic agents have moved into clinical trials. The search for extrarenal pathways in salt-sensitive hypertension has led to significant investigation into the renin–angiotensin–aldosterone system, the sympathetic nervous system, and the endothelin system. More recently, there has been increasing interest in the gastrorenal axis and specifically in gastrointestinal sodium transport. In the report from Jose and Raj (pp. 403–409), the authors explore the interplay of the gut microbiome with sodium transport and blood pressure regulation within the context of genetic and epigenetic regulation. This highlights mechanisms of obesity-associated hypertension [1] and the contribution of overnutrition to gastrointestinal regulation of sodium transport. These themes are continued by Spencer and Greasley (pp. 410–416) in a review of agents targeting the gut sodium– hydrogen exchanger to reduce gastrointestinal sodium absorption. These therapeutics may have
significant implications for managing salt-sensitive hypertension and volume overload in patients with kidney, hepatic, and/or cardiovascular disease. The authors present a state-of-the-art discussion on these compounds and where they stand in development. To continue, a useful strategy in the management of resistant hypertension is antagonism of the mineralocorticoid receptor. This strategy, however, has been limited by the attendant risk for hyperkalemia in patients with chronic kidney disease. The recent development of nonsteroidal antagonists may attenuate some of this risk and represents a critical advancement in the field. Kolkhof et al. (pp. 417–424) present a thorough discussion of two compounds in development and one ready for market. Inappropriate activation of the renin–angiotensin–aldosterone system and oxidant stress contribute significantly to the risk for cardiovascular and kidney disease. Despite decades of work targeting oxidant stress, a clinically useful compound has yet to be approved by the Food and Drug Administration. In this issue, Montezano et al. (pp. 425–433) explore the emerging role of Nox5 in cardiovascular tissue, the importance of Nox5 as a target in hypertension, and limitations in the study of prior antioxidant compounds. In total, this issue of Pharmacology and Therapeutics will help the reader understand two emerging areas – the gastrorenal axis and mineralocorticoid receptor antagonism/redox modulation – of drug a Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, bResearch Service, Harry S. Truman Memorial Veterans Hospital and cDivisions of Nephrology and Hypertension and Endocrinology and Metabolism, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA
Correspondence to Adam Whaley-Connell, DO, MSPH, Associate Chief of Staff for Research and Development, Harry S. Truman Memorial Veterans Hospital, Associate Professor of Medicine, University of Missouri-Columbia School of Medicine, 800 Hospital Dr, Columbia, MO 65201, USA. E-mail: [email protected] Curr Opin Nephrol Hypertens 2015, 24:401–402 DOI:10.1097/MNH.0000000000000156
1062-4821 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-nephrolhypertens.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pharmacology and therapeutics
development in the management of hypertension, particularly in those with chronic kidney disease.
Conflicts of interest There are no conflicts of interest.
Acknowledgements None.
REFERENCE
Financial support and sponsorship None.
402
www.co-nephrolhypertens.com
1.
Jindal A, Brietzke S, Sowers JR. Obesity and the cardiorenal metabolic syndrome: therapeutic modalities and their efficacy in improving cardiovascular and renal risk factors. Cardiorenal Med 2012; 2:314–327.
Volume 24 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
