Pharmacological interventions for heart failure in people with chronic kidney disease

Lunney, Meaghan; Ruospo, Marinella; Natale, Patrizia; Quinn, Robert R.; Ronksley, Paul E.; Konstantinidis, Ioannis T.; Palmer, Suetonia C.; Strippoli, Giovanni F.M.; Ravani, Pietro

doi:10.1002/14651858.cd012466.pub2

Cited by 19 publications

(15 citation statements)

References 865 publications

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“…Both miR-122-3p and miR-122-5p are widely expressed in endothelial cells (ECs), cardiomyocytes (CMs), cardiac fibroblasts (CFs), adipocytes, vascular smooth muscle cells (VSMCs) and adventitial fibroblasts (AFs) in the cardiovascular system (Table 1; Fig. 3) [1,6,9,10]. Recently, administration of a miR-122 inhibitor was shown to reduce the key transforming growth factor-β (TGF-β)-induced fibrotic signaling pathway, promotes collagen synthesis and stimulates fibrinogenesis, consequently resulting in the accumulation of fibroblasts and extracellular matrix (ECM), in hypertension and cardiovascular diseases [2,3,9,11].…”

Section: Biogenesis and Biological Effects Of Mir-122mentioning

confidence: 99%

“…MiR-122 levels were shown to be upregulated in patients with atherosclerotic lesions, and serum miR-122 levels were positively correlated with atherosclerotic severity [ 20 , 48 , 49 ]. In fact, miR-122 promotes proinflammatory factors and oxidant injury in the liver and cardiovascular system [ 10 , 12 , 13 ]. Thus, potential usage of miR-122 antagonism in treatment of inflammatory injury may represent a novel therapeutic approach for atherosclerosis.…”

Section: Roles Of Mir-122 In Atherosclerosismentioning

confidence: 99%

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Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases

et al. 2020

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Fibrotic diseases cause annually more than 800,000 deaths worldwide, where of the majority accounts for cardiovascular fibrosis, which is characterized by endothelial dysfunction, myocardial stiffening and reduced dispensability. MicroRNAs (miRs), small noncoding RNAs, play critical roles in cardiovascular dysfunction and related disorders. Intriguingly, there is a critical link among miR-122, cardiovascular fibrosis, sirtuin 6 (SIRT6) and angiotensin-converting enzyme 2 (ACE2), which was recently identified as a coreceptor for SARS-CoV2 and a negative regulator of the rennin-angiotensin system. MiR-122 overexpression appears to exacerbate the angiotensin II-mediated loss of autophagy and increased inflammation, apoptosis, extracellular matrix deposition, cardiovascular fibrosis and dysfunction by modulating the SIRT6-Elabela-ACE2, LGR4-β-catenin, TGFβ-CTGF and PTEN-PI3K-Akt signaling pathways. More importantly, the inhibition of miR-122 has proautophagic, antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic effects. Clinical and experimental studies clearly demonstrate that miR-122 functions as a crucial hallmark of fibrogenesis, cardiovascular injury and dysfunction. Additionally, the miR-122 level is related to the severity of hypertension, atherosclerosis, atrial fibrillation, acute myocardial infarction and heart failure, and miR-122 expression is a risk factor for these diseases. The miR-122 level has emerged as an early-warning biomarker cardiovascular fibrosis, and targeting miR-122 is a novel therapeutic approach against progression of cardiovascular dysfunction. Therefore, an increased understanding of the cardiovascular roles of miR-122 will help the development of effective interventions. This review summarizes the biogenesis of miR-122; regulatory effects and underlying mechanisms of miR-122 on cardiovascular fibrosis and related diseases; and its function as a potential specific biomarker for cardiovascular dysfunction.

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Section: Biogenesis and Biological Effects Of Mir-122mentioning

confidence: 99%

Section: Roles Of Mir-122 In Atherosclerosismentioning

confidence: 99%

Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases

et al. 2020

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“…In this line, utilization of balanced solutions with physiological concentrations of chloride (Ringer's lactate and Plasmalyte) prevents the development of metabolic acidosis and is associated with lower sK + levels compared to NaCl 0.9% (38). Other strategies that have shown bene t by decreasing potassium in patients with AKI are calcium salts, which increase the cardiac threshold potential and stabilizes the myocellular membrane (39); hypertonic sodium solution, which increases the action potential rising velocity in isolated cardiomyocytes (40); hypertonic sodium bicarbonate (150 mL of 8.4% sodium bicarbonate over 20 min) in patients with metabolic acidosis (34); polarizing solutions, including use of insulin (41) and β-adrenergic agonists (42) to shift potassium from the extracellular to the intracellular compartment; loop diuretics, which have shown to be effective in patients with hyperK and concomitant volume overload (43); and nally, potassiumbinding agents (44). It is very important to keep monitoring sK + levels when implementing strategies to decrease them.…”

Section: Discussionmentioning

confidence: 99%

Serum potassium trajectory during AKI and mortality risk

Chávez-Íñiguez

Maggiani-Aguilera

Quevedo

et al. 2022

Preprint

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Background: Kidneys play a primary role in potassium homeostasis. The association between potassium (sK+) level and mortality or the need for kidney replacement therapy (KRT) during acute kidney injury (AKI) has not been adequately explored. Methods: In this prospective cohort study, AKI patients admitted to the Hospital Civil de Guadalajara were enrolled from August 2017 to June 2021 with AKI. We divided patients into 8 groups based on the serum potassium level trajectories up to ten days following hospitalization, (1) normokalemia (normoK), defined as sK+ values between 3.5 and 5.5 mEq/L; (2) corrected hyperkalemia (hyperK), sK+ > 5.5 mEq/L on hospital admission and decreased to normoK; (3) corrected hypokalemia (hypoK), sK+ < 3.5 mEq/L on hospital admission and increased to normoK; (4) fluctuating potassium, sK+ increased / decreased in and out of normoK parameters; (5) uncorrected hypoK, sK+ < 3.5 mEq/L; (6) normoK to hypoK, sK+ that were normal on hospital admission and decreased to hypoK and never went back to normal; (7) normoK to hyperK, sK+ that were normal on hospital admission and increased to hyperK and never went back to normal; (8) uncorrected hyperK, sK+ > 5.5 mEq/L. We assessed the association of serum potassium trajectories with mortality and the need for KRT (secondary objective). Results: A total of 311 AKI patients were included. The mean age was 52.6 years, and 182 (58.6%) were male. AKI stage 3 was present in 199 (63.9%). KRT started in 112 (36%) patients, and 66 (21.2%) died. After adjusting for confounders, 10-day hospital mortality was significantly higher in group 7 and 8 (OR, 1.37 and 1.63, p = <0.05, for both, respectevely), and KRT initiation was higher only in group 8 (OR 1.40, p = < 0.05) compared with group 1. Mortality in different subgroups of patients in group 8 did not change the primary results.Conclusion: In our prospective cohort, most patients with AKI had alterations in sK+. NormoK to hyperK and Uncorrected hyperK were associated with death, while only uncorrected hyperK was correlated with the need for KRT.

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“…the capability to adequately respond to inotropic support (dobutamine) together with a reduction in left ventricular filling pressure. The positive effects of SAR101099 in pigs are particularly interesting because RAAS inhibition with ramipril was much less beneficial than in rats, consistent with its limited protective effect in human CKD patients with heart failure (Lunney et al, 2020).…”

Section: Downloaded Frommentioning

confidence: 91%

Potential Therapeutic Value of Urotensin II Receptor Antagonist in Chronic Kidney Disease and Associated Comorbidities

Ozoux¹,

Briand²,

Pelat³

et al. 2020

J Pharmacol Exp Ther

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Chronic kidney disease (CKD) remains a common disorder leading to growing health and economic burden without curative treatment. In diabetic patients, CKD may result from a combination of metabolic and non-metabolic-related factors with mortality mainly driven by cardiovascular events. The marked overactivity of the urotensinergic system in diabetic patients implicates this vasoactive peptide as a possible contributor to the pathogenesis of renal as well as heart failure. Previous preclinical studies with urotensin II (UII) antagonists in chronic kidney disease were based on simple endpoints that did not reflect the complex etiology of the disease. Given this, our studies revisited the therapeutic value of UII antagonism in CKD and extensively characterize 1-({[6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2-methylphenyl)pyridin-2-yl]carbonyl}amino) cyclohexanecarboxylic acid hydrochloride (SAR101099), a potent, selective and orally long-acting UT competitive antagonist inhibiting not only UII but also urotensin related peptide activities. SR101099 treatment more than halved proteinurea and albumin/creatinine ratio in spontaneously-hypertensive stroke-prone-(SHR-SP) rats fed with salt/fat diet and Dahl-salt-sensitive rats, respectively, and halved albuminuria in streptozotocin-induced diabetes rats. Importantly, these effects were accompanied by a decrease in mortality by 50% in SHR-SP and by 35% in the Dahl salt-sensitive rats. SAR101099 was also active on CKD-related cardiovascular pathologies, and partly preserved contractile reserve in models of heart failure induced by myocardial infarction or ischemia/reperfusion in rats and pigs, respectively. SAR101099 exhibited a good safety/tolerability profile at all tested doses in clinical phase-I studies. Together, these data suggest that CKD patient selection considering comorbidities together with new stratification modalities should unveil the urotensin antagonists' therapeutic potential.

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Pharmacological interventions for heart failure in people with chronic kidney disease

Cited by 19 publications

References 865 publications

Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases

Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases

Serum potassium trajectory during AKI and mortality risk

Potential Therapeutic Value of Urotensin II Receptor Antagonist in Chronic Kidney Disease and Associated Comorbidities

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