Evolution of Cardiovascular Disease During the Transition to End-Stage Renal Disease

Bansal, Nisha

doi:10.1016/j.semnephrol.2016.12.002

Cited by 36 publications

(30 citation statements)

References 126 publications

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“…Cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of death in the United States. 25 While aberrant and excessive organ fibrosis underlie the pathogenesis of both CVDs and CKDs, no effective anti-fibrotic therapy currently exists. Here we report a novel, fibrosis-impeding role of L002 which is a cell permeable, small molecule inhibitor of FATp300.…”

Section: Discussionmentioning

confidence: 99%

A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

et al. 2017

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Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300—p300 with intrinsic factor acetyltransferase activity—is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis. Additionally, we examine the effects of L002 on cellular pro-fibrogenic processes and provide mechanistic insights into its antifibrogenic action. Utilizing cardiac fibroblasts, podocytes, and mesangial cells, we demonstrate that L002 blunts FATp300-mediated acetylation of specific histones. Further, incubating cells with L002 suppresses several pro-fibrogenic processes including cellular proliferation, migration, myofibroblast differentiation and collagen synthesis. Importantly, systemic administration of L002 in mice reduces hypertension-associated pathological hypertrophy, cardiac fibrosis and renal fibrosis. The anti-hypertrophic and anti-fibrotic effects of L002 were independent of blood pressure regulation. Our work solidifies the role of epigenetic regulator FATp300 in fibrogenesis and establishes it as a pharmacological target for reducing pathological matrix remodeling and associated pathologies. Additionally, we discover a new therapeutic role of L002, as it ameliorates hypertension-induced cardio-renal fibrosis and antagonizes pro-fibrogenic responses in fibroblasts, podocytes and mesangial cells.

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Section: Discussionmentioning

confidence: 99%

A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

et al. 2017

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“…The condition leads to a disturbed internal milieu, which may substantially change the pharmacokinetic and pharmacodynamic properties of the drug (Gabardi & Abramson 2005). CKD is also associated with accelerated heart disease (Bansal 2017) and many antidepressants are potentially cardiotoxic (Assimon et al . 2019).…”

Section: Introductionmentioning

confidence: 99%

Antidepressant Usage in Haemodialysis Patients: Evidence of Sub‐Optimal Practice Patterns

Guirguis

Chilcot

Almond

et al. 2020

Journal of Renal Care

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SUMMARY Background Depression is common in patients on haemodialysis and associated with adverse outcomes. Antidepressant use is widespread though evidence of efficacy is limited. Objectives To study antidepressant management practices in patients on haemodialysis with reference to NICE guidelines on management of depression in adults with chronic physical health problems. Design Prospective, multicentre, longitudinal cohort study with 6–15 month follow‐up. Participants Patients on haemodialysis established on antidepressant medication. Measurements Baseline assessment of mood was undertaken using Beck Depression Inventory (BDI‐II). Demographic, clinical and medication data were also collected. Changes in clinical and life circumstances and medication during follow‐up were recorded. At follow‐up, BDI‐II was reassessed and diagnostic psychiatric assessment undertaken. Results Forty‐one patients were studied. General practitioners were the main prescribers (68%). Ten agents were in use, the commonest being Citalopram (39%). Doses were often suboptimal. At baseline, 30 patients had high BDI‐II scores (≥16) and 22 remained high at follow‐up. Eleven had BDI‐II < 16 at baseline. In five, this increased on follow‐up to ≥16. Sixteen patients (39%) had no medication review during follow‐up, 14 (34%) had a dose review, and 11 (27%) a medication change. On psychiatric assessment at follow‐up, eight patients had current major depressive disorder (MDD), seven recurrent and 20 evidence of past MDD. Six displayed no evidence of ever having MDD. Conclusions Antidepressant management in patients on haemodialysis reflected poor drug selection, overprescription, under‐dosing and inadequate follow‐up suggesting sub‐optimal adherence to NICE guidelines. Most patients had high depression scores at follow‐up. Antidepressant use in haemodialysis requires reappraisal.

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“…Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients [1]. Chronic kidney disease (CKD)-related cardiomyopathy, which has been termed “uremic cardiomyopathy” [2], has a significant contribution to these adverse cardiac outcomes [3].…”

Section: Introductionmentioning

confidence: 99%

Relationship of Serum Soluble Klotho Levels and Echocardiographic Parameters in Patients on Maintenance Hemodialysis

Zhang

Guo

et al. 2019

Kidney Blood Press Res

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Background: Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients. Uremic cardiomyopathy, characterized by myocardial hypertrophy and fibrosis, has a significant contribution to these adverse cardiac outcomes. The protective effect of soluble Klotho (s-Klotho) on myocardial damage was demonstrated in in vitro and animal experiments. However, data from MHD patients is limited. The present study was designed to identify potential correlations between echocardiographic parameters and serum s-Klotho levels in MHD patients. Methods: This is a cross-sectional study involving 105 MHD patients from the Dialysis Center of Capital Medical University affiliated Beijing Friendship Hospital between March and October 2014. The general information for each patient was recorded. Fasting blood samples were collected prior to hemodialysis during the mid-week session in all patients. The echocardiogram and left lateral lumbar spine radiograph were performed after the same mid-week session. The dialysis records for each session within 3 months before the blood tests were documented. According to the quartiles of s-Klotho levels, patients were divided into four groups (Group 1–4). The demographic and clinical characteristics, echocardiographic parameters, and abdominal aortic calcification scores among the groups were compared. Results: The enrolled 105 patients were predominantly male (54.3%) with an average age of 59.9 ± 11.2 years. Previous hemodialysis durations were 76 (42–133) months. Sixteen (15.2%) patients had diabetes mellitus. Mean serum s-Klotho level was 411.83 ± 152.95 pg/mL, and the 25th percentile, 50th percentile, and 75th percentile values of serum s-Klotho levels were 298.9, 412, and 498.2 pg/mL, respectively. Individuals in the bottom quartile of s-Klotho levels (Group 1) had significantly increased interventricular septal thickness (IVST) compared to those in the other three quartiles of s-Klotho levels (Group 1: 1.12 ± 0.16 cm; vs. Group 2: 1.12 ± 0.16 cm, p = 0.008; vs. Group 3: 0.94 ± 0.13 cm, p < 0.001; vs. Group 4: 1.03 ± 0.1 5 cm, p = 0.022). There were significant differences in the ratios of IVST and posterior wall thickness (PWT) between patients of Group 1 and Group 3 (1.12 ± 0.1 2 vs. 1.00 ± 0.1 4, p = 0.004). No significant differences were found for other parameters among the groups. The univariate correlation analyses showed that gender (r = –0.211, p = 0.030), Kt/V urea (r = –0.240, p = 0.014), hypersensitive C reactive protein (hs-CRP) (r = 0.196, p = 0.045), and serum s-Klotho levels (r = –0.260, p = 0.007) significantly correlated with IVST. Ultimately, only hs-CRP and serum s-Klotho levels were entered into a multiple regression model. Conclusions: The present study showed that patients with lower circulating s-Klotho levels were more often associated with larger IVST and greater ratios of IVST and PWT. There was an independent association between s-Klotho and IVST, and lower s-Klotho levels seem to be a potential risk factor of uremic...

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Evolution of Cardiovascular Disease During the Transition to End-Stage Renal Disease

Cited by 36 publications

References 126 publications

A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

Antidepressant Usage in Haemodialysis Patients: Evidence of Sub‐Optimal Practice Patterns

Relationship of Serum Soluble Klotho Levels and Echocardiographic Parameters in Patients on Maintenance Hemodialysis

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