Cardiorenal syndrome type 4: From chronic kidney disease to cardiovascular impairment

Basile, Antonio; Clementi, Anna; Virzì, Grazia Maria; Brocca, Alessandra; Cal, Massimo de; Scarfia, Viviana R.; Zanoli, Luca; Ronco, Claudio; Corrao, Salvatore; Malatino, Lorenzo

doi:10.1016/j.ejim.2016.02.019

Cited by 33 publications

(33 citation statements)

References 75 publications

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“…Cardiovascular disease remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), particularly in patients who elect to undergo dialysis treatment (1,2). Indoxyl sulfate (IS) is a typical protein-bound uremic toxin, which is challenging to remove using current dialysis techniques, and serves a central role in cardiac damage among patients with CKD (3).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate‑induced cardiomyocyte toxicity

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate‑induced cardiomyocyte toxicity

et al. 2018

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“…Almost 40% of diabetes sufferers develop diabetic nephropathy (DN), which has thus become the leading cause of end stage renal disease (ESRD) in urbanized countries [1]. Patients with CKD are not only at an increased risk of end-stage renal disease, but also cardiovascular disease and death [2,3]. Novel targets for improved DN management urgently need to be identified as ESRD can manifest despite strict glycaemic control and the application of various therapeutic approaches [4].…”

Section: Introductionmentioning

confidence: 99%

Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to Interfering with Mesangial Cell Collagen Production in a Hyperglycaemic Setting

et al. 2016

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Extracellular vesicles (EVs) that are derived from stem cells are proving to be promising therapeutic options. We herein investigate the therapeutic potential of EVs that have been derived from different stem cell sources, bone-marrow (MSC) and human liver (HLSC), on mesangial cells (MCs) exposed to hyperglycaemia. By expressing a dominant negative STAT5 construct (ΔNSTAT5) in HG-cultured MCs, we have demonstrated that miR-21 expression is under the control of STAT5, which translates into Transforming Growth Factor beta (TGFβ) expression and collagen production. A number of approaches have been used to show that both MSC- and HLSC-derived EVs protect MCs from HG-induced damage via the transfer of miR-222. This resulted in STAT5 down-regulation and a decrease in miR-21 content, TGFβ expression and matrix protein synthesis within MCs. Moreover, we demonstrate that changes in the balance between miR-21 and miR-100 in the recipient cell, which are caused by the transfer of EV cargo, further contribute to providing beneficial effects. Interestingly, these effects were only detected in HG-cultured cells. Finally, it was found that HG reduced the expression of the nuclear encoded mitochondrial electron transport chain (ETC) components, CoxIV. It is worth noting that EV administration can rescue CoxIV expression in HG-cultured MCs. These results thus demonstrate that both MSC- and HLSC-derived EVs transfer the machinery needed to preserve MCs from HG-mediated damage. This occurs via the horizontal transfer of functional miR-222 which directly interferes with damaging cues. Moreover, our data indicate that the release of EV cargo into recipient cells provides additional therapeutic advantages against harmful mitochondrial signals.

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“…CRS type 4, or chronic renocardiac syndrome, has been defined as "chronic abnormalities in renal function leading to cardiac disease" and recognizes the extreme burden of CVD in patients with CKD such as chronic glomerular disease and autosomal dominant polycystic kidney disease (ADPKD). This is the condition where primary CKD contributes a reduction in cardiac function such as cardiac remodeling, left ventricular diastolic dysfunction or hypertrophy, and/or an increased risk for CV events such as MI, heart failure or stroke [76].…”

Section: Chronic Cardiorenal and Renocardiac Syndrome Interactionmentioning

confidence: 99%

Traditional, Nontraditional, and Uremia-Related Threats for Cardiovascular Disease in Chronic Kidney Disease

Rebić¹,

Hamzić-Mehmedbašić²

2018

Chronic Kidney Disease - From Pathophysiology to Clinical Improvements

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As many as 40-50% of all patients suffering from chronic kidney disease (CKD) die from reasons related to cardiovascular disease (CVD). The severity of the illness is directly connected to higher mortality caused by cardiovascular factors, with the cause of the CKD not as significant for the relationship. This risk of high cardiovascular mortality and morbidity is actually so high that it surpasses the risk of the patients reaching end-stage renal disease. Within the context of CKD, CVD has certain distinct characteristics. Left ventricular hypertrophy (LVH) is commonly used as a predictor of cardiovascular (CV) mortality. The striking cardiac interstitial fibrosis, a crucial part of uremic cardiomyopathy, and nonobstructive vascular diseases are highly prevalent CV pathology in CKD patients. Traditional risk factors appear to be of less importance in the CKD population compared to the general population but have been hypothesized as uremic toxins as a risk factor of cardiorenal syndrome. In this chapter, we discuss the importance of renal function in the pathophysiology of heart failure. We also elaborate on the novel understanding of chronic kidney disease and its role in cardiovascular disease progression.

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Cardiorenal syndrome type 4: From chronic kidney disease to cardiovascular impairment

Cited by 33 publications

References 75 publications

Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate‑induced cardiomyocyte toxicity

Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate‑induced cardiomyocyte toxicity

Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to Interfering with Mesangial Cell Collagen Production in a Hyperglycaemic Setting

Traditional, Nontraditional, and Uremia-Related Threats for Cardiovascular Disease in Chronic Kidney Disease

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