American Society of Hypertension Self-Assessment Guide
Basic science: Pathophysiology: the CardioRenal Metabolic Syndrome

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    The pathophysiology of CRS constitutes an interplay of multifaceted dysfunctional cardiac and renal factors, including insulin resistance, hypertension, and dyslipidemia. The overlapping of these two distinct processes results in subsequent heart failure (HF) associated with diastolic dysfunction, HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF), left ventricular hypertrophy, and kidney failure associated with acute injury and CKD [3,4]. Hyperfiltration, characterized by a gradual loss of kidney function and an increase in albuminuria, is a critical process in the pathogenesis of kidney disease in people with diabetes [5].

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    Thus, the redox imbalance scenario favors CRMS and contributes to the development of complications that trigger this syndrome. The CRMS, defined as combined disorders of heart and kidney, is characterized by impaired coronary blood flow, impaired diastolic relaxation, impaired ischemic reconditioning, renal hyper-filtration, proteinuria, glomerular sclerosis, tubule-interstitial fibrosis, and decreased GFR (glomerular filtration rate), with significant impact on life expectancy and mortality(Francisqueti et al., 2017; Rangaswami et al., 2019; Silva Junior et al., 2017; van der Velde et al., 2011; Whaley-Connell and Sowers, 2014). In order to prevent or treat cardiorenal metabolic syndrome, it is important to consider treatment strategies for modulating the pathophysiological processes involved in this disease.

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  • Autophagy as an emerging target in cardiorenal metabolic disease: From pathophysiology to management

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    Earlier conceptualizations of cardiorenal metabolic syndrome mainly focused on obesity with insulin resistance as a core feature. A large volume of clinical and experimental evidence depicted the pathophysiological mechanisms of cardiorenal metabolic syndrome including identification of genes responsible for syndromic or non-syndromic monogenic oligogenic or polygenic anomalies and interplays among genetic and epigenetic factors (Whaley-Connell & Sowers, 2014; Y. Zhang & Ren, 2016). More recent findings have depicted an essential role for autophagy, a cellular process of degrading long-lived, injured proteins and organelles (Mizushima, 2018; S. Yan, Huda, Khambu, & Yin, 2017), in the pathogenesis of cardiorenal metabolic syndrome.

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This article is part of the American Society of Hypertension Self-Assessment Guide series. For other articles in this series, visit the JASH home page at www.ashjournal.com.

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