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International Journal of Molecular... Jul 2020In Chronic Kidney Disease (CKD) patients, elevated blood pressure (BP) is a frequent finding and is traditionally considered a direct consequence of their sodium... (Review)
Review
In Chronic Kidney Disease (CKD) patients, elevated blood pressure (BP) is a frequent finding and is traditionally considered a direct consequence of their sodium sensitivity. Indeed, sodium and fluid retention, causing hypervolemia, leads to the development of hypertension in CKD. On the other hand, in non-dialysis CKD patients, salt restriction reduces BP levels and enhances anti-proteinuric effect of renin-angiotensin-aldosterone system inhibitors in non-dialysis CKD patients. However, studies on the long-term effect of low salt diet (LSD) on cardio-renal prognosis showed controversial findings. The negative results might be the consequence of measurement bias (spot urine and/or single measurement), reverse epidemiology, as well as poor adherence to diet. In end-stage kidney disease (ESKD), dialysis remains the only effective means to remove dietary sodium intake. The mismatch between intake and removal of sodium leads to fluid overload, hypertension and left ventricular hypertrophy, therefore worsening the prognosis of ESKD patients. This imposes the implementation of a LSD in these patients, irrespective of the lack of trials proving the efficacy of this measure in these patients. LSD is, therefore, a rational and basic tool to correct fluid overload and hypertension in all CKD stages. The implementation of LSD should be personalized, similarly to diuretic treatment, keeping into account the volume status and true burden of hypertension evaluated by ambulatory BP monitoring.
Topics: Blood Pressure; Diet, Sodium-Restricted; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Prognosis; Renal Dialysis; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium Chloride, Dietary; Water-Electrolyte Imbalance
PubMed: 32635265
DOI: 10.3390/ijms21134744 -
FASEB Journal : Official Publication of... Feb 2020Local and systemic factors that influence renal structure and function in aging are not well understood. The secretory protein C1q/TNF-related protein 1 (CTRP1)...
Local and systemic factors that influence renal structure and function in aging are not well understood. The secretory protein C1q/TNF-related protein 1 (CTRP1) regulates systemic metabolism and cardiovascular function. We provide evidence here that CTRP1 also modulates renal physiology in an age- and sex-dependent manner. In mice lacking CTRP1, we observed significantly increased kidney weight and glomerular hypertrophy in aged male but not female or young mice. Although glomerular filtration rate, plasma renin and aldosterone levels, and renal response to water restriction did not differ between genotypes, CTRP1-deficient male mice had elevated blood pressure. Echocardiogram and pulse wave velocity measurements indicated normal heart function and vascular stiffness in CTRP1-deficient animals, and increased blood pressure was not due to greater salt retention. Paradoxically, CTRP1-deficient mice had elevated urinary sodium and potassium excretion, partially resulting from reduced expression of genes involved in renal sodium and potassium reabsorption. Despite renal hypertrophy, markers of inflammation, fibrosis, and oxidative stress were reduced in CTRP1-deficient mice. RNA sequencing revealed alterations and enrichments of genes in metabolic processes in CTRP1-deficient animals. These results highlight novel contributions of CTRP1 to aging-associated changes in renal physiology.
Topics: Adipokines; Animals; Blood Pressure; Hypertension; Hypertrophy; Inflammation; Kidney; Mice, Knockout; Signal Transduction
PubMed: 31908037
DOI: 10.1096/fj.201900558RR -
Nature Communications Jun 2023Loss of a kidney results in compensatory growth of the remaining kidney, a phenomenon of considerable clinical importance. However, the mechanisms involved are largely...
Loss of a kidney results in compensatory growth of the remaining kidney, a phenomenon of considerable clinical importance. However, the mechanisms involved are largely unknown. Here, we use a multi-omic approach in a unilateral nephrectomy model in male mice to identify signaling processes associated with renal compensatory hypertrophy, demonstrating that the lipid-activated transcription factor peroxisome proliferator-activated receptor alpha (PPARα) is an important determinant of proximal tubule cell size and is a likely mediator of compensatory proximal tubule hypertrophy.
Topics: Male; Mice; Animals; Multiomics; Kidney; Nephrectomy; Hypertrophy; Kidney Tubules, Proximal
PubMed: 37328470
DOI: 10.1038/s41467-023-38958-9 -
Scientific Reports Sep 2023The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can...
The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can indirectly affect cardiac function and heart morphology. Notch3-deficiency causes vascular smooth muscle cell (VSMC) loss in the vasculature but the consequences for the heart remain largely elusive. Here, we demonstrate that Notch3 mice have enlarged hearts with left ventricular hypertrophy and mild fibrosis. Cardiomyocytes were hypertrophic but not hyperproliferative, and the expression of several cardiomyocyte markers, including Tnt2, Myh6, Myh7 and Actn2, was altered. Furthermore, expression of genes regulating the metabolic status of the heart was affected: both Pdk4 and Cd36 were downregulated, indicating a metabolic switch from fatty acid oxidation to glucose consumption. Notch3 mice furthermore showed lower liver lipid content. Notch3 was expressed in heart VSMC and pericytes but not in cardiomyocytes, suggesting that a perturbation of Notch signalling in VSMC and pericytes indirectly impairs the cardiomyocytes. In keeping with this, Pdgfb mice, characterized by reduced numbers of VSMC and pericytes, showed left ventricular and cardiomyocyte hypertrophy. In conclusion, we demonstrate that reduced Notch3 or PDGFB signalling in vascular mural cells leads to cardiomyocyte dysfunction.
Topics: Animals; Mice; Becaplermin; Cardiomegaly; Hypertrophy, Left Ventricular; Lipid Metabolism; Myocytes, Cardiac; Proto-Oncogene Proteins c-sis
PubMed: 37699967
DOI: 10.1038/s41598-023-42010-7 -
Journal of the American Veterinary... Nov 2023Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac...
OBJECTIVE
Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.
ANIMALS
43 client-owned cats with subclinical HCM.
METHODS
Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.
RESULTS
No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.
CLINICAL RELEVANCE
Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.
Topics: Animals; Cats; Cardiomyopathy, Hypertrophic; Cat Diseases; Heart; Hypertrophy, Left Ventricular; Myocardium; Sirolimus; Delayed-Action Preparations
PubMed: 37495229
DOI: 10.2460/javma.23.04.0187 -
Circulation Journal : Official Journal... 2013
Topics: Hair; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Magnesium; Male; Renal Dialysis
PubMed: 24200847
DOI: 10.1253/circj.cj-13-1294 -
Biomedicine & Pharmacotherapy =... Aug 2022Galangin is a polyphenolic compound found in Alpinia officinarum and propolis. This study investigated the effect of galangin on blood pressure, the renin angiotensin...
Galangin is a polyphenolic compound found in Alpinia officinarum and propolis. This study investigated the effect of galangin on blood pressure, the renin angiotensin system (RAS), cardiac and kidney alterations and oxidative stress in two-kidney one-clipped (2K-1C) hypertensive rats. Hypertension was induced in male Sprague Dawley rats (180-220 g), and the rats were given galangin (30 and 60 mg/kg) and losartan (10 mg/kg) for 4 weeks (n = 8/group). Galangin decreased hypertension and cardiac dysfunction and hypertrophy, which was related to the reducing circulation angiotensin converting enzyme (ACE) activity and angiotensin II concentration (p < 0.05). These effects were consistent with the reduced overexpression of angiotensin II receptor type 1 (ATR), transforming growth factor beta 1 (TGF-β1) and collagen type I (Col I) protein in cardiac tissue (p < 0.05). Additionally, renal artery occlusion, procedure-induced kidney dysfunction and fibrosis were attenuated in the galangin-treated group. Galangin treatment normalized the overexpression of ATR and NADPH oxidase 4 (Nox-4) protein and normalized the downregulation of nuclear factor-erythroid Factor 2-related Factor 2 (Nrf-2) and haem oxygenase 1 (HO-1) in 2K-1C rats (p < 0.05). Galangin exhibited antioxidative effects, as it reduced systemic and tissue oxidative stress markers and increased catalase activity in 2K-1C rats (p < 0.05). In conclusion, galangin attenuated hypertension, renin-angiotensin system activation, cardiorenal damage and oxidative stress induced by renal artery stenosis in rats. These effects might be associated with modulation of the expression of ATR, TGF-β1 and Col I protein in the heart as well as ATR/Nox-4 and Nrf-2/HO-1 protein in renal tissue in hypertensive rats.
Topics: Animals; Flavonoids; Hypertension; Hypertrophy; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Renal Artery; Transforming Growth Factor beta1
PubMed: 35687907
DOI: 10.1016/j.biopha.2022.113231 -
Blood Purification 2006Uric acid might often be regarded as a simple marker of renal disease. Although it is well known that hyperuricemia causes gout which is associated with renal... (Review)
Review
Uric acid might often be regarded as a simple marker of renal disease. Although it is well known that hyperuricemia causes gout which is associated with renal insufficiency and cardiovascular disease, one might think that it could attribute to the intrarenal urate crystal, but not to uric acid per se. In order to clarify the role of uric acid in the kidney, we hypothesized that uric acid causes renal disease. To generate mild hyperuricemia without intrarenal crystal in rats, we used low doses of an uricase inhibitor (2% oxonic acid). Hyperuricemia induced systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis, and macrophage infiltration in normal rat kidney. In progressive renal disease, such as cyclosporine nephropathy and remnant kidney in rat, uric acid accelerated the progression of renal disease. Thus, we concluded that uric acid is not a simple marker, but a cause of renal disease.
Topics: Animals; Arteriosclerosis; Biomarkers; Enzyme Inhibitors; Humans; Hypertension; Hypertrophy; Hyperuricemia; Kidney; Kidney Diseases; Oxonic Acid; Rats; Urate Oxidase; Uric Acid
PubMed: 16361844
DOI: 10.1159/000089440 -
The Journal of the Royal College of... Mar 2017Cardiovascular disease is common in patients with chronic kidney disease. The increased risk of cardiovascular disease seen in this population is attributable to both... (Review)
Review
Cardiovascular disease is common in patients with chronic kidney disease. The increased risk of cardiovascular disease seen in this population is attributable to both traditional and novel vascular risk factors. Risk of sudden cardiac or arrhythmogenic death is greatly exaggerated in chronic kidney disease, particularly in patients with end stage renal disease where the risk is roughly 20 times that of the general population. The reasons for this increased risk are not entirely understood and while atherosclerosis is accelerated in the presence of chronic kidney disease, premature myocardial infarction does not solely account for the excess risk. Recent work demonstrates that the structure and function of the heart starts to alter early in chronic kidney disease, independent of other risk factors. The implications of cardiac remodelling and hypertrophy may predispose chronic kidney disease patients to heart failure, arrhythmia and myocardial ischaemia. Further research is needed to minimise cardiovascular risk associated with structural and functional heart disease associated with chronic kidney disease.
Topics: Cardiovascular Diseases; Dyslipidemias; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Organ Size; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 28569289
DOI: 10.4997/JRCPE.2017.117 -
Blood Purification 2018Accelerated ageing is observed in patients with chronic kidney disease (CKD)/end-stage renal disease. Premature vascular aging and arterial stiffening are the most... (Review)
Review
Accelerated ageing is observed in patients with chronic kidney disease (CKD)/end-stage renal disease. Premature vascular aging and arterial stiffening are the most characteristic features of this "progeria" that is already observed in those with the early stages of CKD. Aortic stiffening is associated with high characteristic impedance, left ventricular hypertrophy, decreased coronary perfusion, and is a strong prognostic marker of mortality and cardiovascular morbidity. With aging, the arterial stiffening is more pronounced in the aorta and central arteries than in peripheral conduit arteries. This leads to progressive decrease and inversion of the arterial stiffness gradient and systemic reflection coefficient, leading to less protection of the microcirculation in the event of high-pressure transmission towards it Arterial stiffening is multifactorial with systemic microinflammation being one of the most important associated factors primarily associated with vascular calcifications.
Topics: Aging; Coronary Circulation; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Microcirculation; Vascular Calcification; Vascular Stiffness
PubMed: 29478047
DOI: 10.1159/000485146