Hypertrophy In Chronic Kidney Disease Research Articles

Finerenone and left ventricular hypertrophy in chronic kidney disease and type 2 diabetes.

Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline. A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR)≥57% from baseline over ≥4weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (Pinteraction=0.1075 for composite CV outcome and Pinteraction=0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (Pinteraction=0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups. In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.

Revitalizing cardiac health in chronic renal failure: the synergistic effects of angiotensin-converting enzyme inhibitors and vitamin C in modulating nitric oxide and left ventricular hypertrophy.

The inducible form of nitric oxide (iNOS) is induced by cytokines and endotoxins. The cardiac-protective effects of nitric oxide (NO) secreted by endothelial NOS are dependent on arginine. Arginine production occurs mainly within the organism, with the kidneys playing a key role in its synthesis and the elimination of asymmetric dimethylarginine (ADM). In the present study the relationship between iNOS, ADMA and left ventricular hypertrophy in chronic kidney disease (CKD) patients and the effect of treatment with angiotensin converting enzyme inhibitor (ACEI) associated with vitamin C (Vit C) were investigated. A longitudinal observational study was conducted on 153 patients with CKD. We studied the correlation between the mean values of iNOS and ADMA in CKD patients and its relationship with left ventricular hypertrophy and the benefit of treating these patients with an associated ACEI and Vit C. The mean age of the patients was 58.85 ±12.75 years. The mean values of iNOS and ADMA were 63.92 ± 0.59 μmol/l and 16.77 ±0.91 μmol/l, respectively. These values increased significantly with the degradation of the renal function (p < 0.05). A significant positive correlation was found between the left ventricular mass index (LVMI) and the two markers, ADMA (0.901 and p = 0001) and iNOS (0.718 and p = 0.0001). After 2 years of treatment with Vit C and ACEI, a significant decrease in LVMI was observed. NO secreted by the iNOS system and ADMAs initiates cardiac remodeling to lead to left ventricular hypertrophy and cardiac fibrosis. ACEIs increase the expression and activity of eNOS and decrease iNOS. Vit C prevents oxidative damage by scavenging ROS species and reagents nitrogen while. iNOS and ADMA accelerate cardiac aging. We conclude that ACEIs combined with Vit C may improve heart health and limite left ventricular hypertrophy in CKD patients.

Left ventricular hypertrophy in chronic kidney disease

Background and Aims : CKD patients have a high prevalence of LVH and an increased cardiovascular risk. In this study we have assessed the prevalence of left ventricular hypertrophy (LVH) and left ventricular geometry in a group of 293 patients with high blood pressure and with stage 2–5 chronic kidney disease (CKD), compared with 289 essential hypertensive patients with normal renal function.

Heparin, klotho, and FGF23: the 3-beat waltz of the discordant heart

Excess fibroblast growth factor (FGF) 23 signaling in patients with chronic kidney disease induces left ventricular hypertrophy. In this issue, Yanucil etal. investigated the interaction of soluble klotho and heparin with FGF23 and FGF receptor isoforms. They concluded that heparin promotes the FGF23-FGF receptor isoform 4 interaction and FGF23 pathogenic effects, supporting an important role of heparin in the pathogenesis of FGF23-mediated left ventricular hypertrophy in chronic kidney disease.

Identification of Major Risk Factors and Non-linear Effects to the Development of Left Ventricular Hypertrophy in Chronic Kidney Disease by Constructing and Validation of Nomograms

BackgroundLeft ventricular hypertrophy (LVH) is a common cardiovascular complication among chronic kidney disease (CKD) patients. The present study aimed to identify major independent risk factors and determine their contribution and relationship to LVH development.MethodsClinical and echocardiographic data of 2002 pre-dialytic CKD patients were retrospectively collected. Independent risk factors for LVH were identified using univariable and multivariable logistic regression. Nomograms together with restricted cubic splines method were employed to explore the effect size and possible non-linear relationship with regard to LVH. A simplified predictive model was constructed and its predictive ability was validated to demonstrate to which extent the identified risk factors accounted for LVH risk.ResultsMultivariable logistic regression identified age, body mass index (BMI), systolic blood pressure (SBP), eGFR and hemoglobin as independent influencing factors for LVH. Nomogram revealed BMI, SBP and hemoglobin concentration as the most important risk factors. Impaired renal function only showed obvious risk for LVH when eGFR declined below 30 ml/min/1.73 m2. Significant threshold effects existed for blood pressure and obesity that the risks for LVH doubled when SBP exceeded 160 mmHg or BMI exceeded 30 kg/m2. The predictive model constructed performed well on both the training and validation cohort using calibration curve, ROC curve and AUC value, with AUC above 0.80 for both the training cohort and the validation cohort.ConclusionsWith the help of nomogram model, we identified five independent factors that explain a large proportion of LVH risk in CKD patients. Among them, major contribution to LVH development was resulted from comorbidities and complications of CKD (hypertension, anemia, obesity) rather than eGFR reduction per se. Non-linear relationship and threshold relationship between eGFR, blood pressure, obesity and LVH risk were also identified.

Glucosylceramide synthase inhibition protects against cardiac hypertrophy in chronic kidney disease

A significant population of patients with chronic kidney disease (CKD) develops cardiac hypertrophy, which can lead to heart failure and sudden cardiac death. Soluble klotho (sKL), the shed ectodomain of the transmembrane protein klotho, protects the heart against hypertrophic growth. We have shown that sKL protects the heart by regulating the formation and function of lipid rafts by targeting the sialic acid moiety of gangliosides, GM1/GM3. Reduction in circulating sKL contributes to an increased risk of cardiac hypertrophy in mice. sKL replacement therapy has been considered but its use is limited by the inability to mass produce the protein. Therefore, alternative methods to protect the heart are proposed. Glucosylation of ceramide catalyzed by glucosylceramide synthase is the entry step for the formation of gangliosides. Here we show that oral administration of a glucosylceramide synthase inhibitor (GCSi) reduces plasma and heart tissue glycosphingolipids, including gangliosides. Administration of GCSi is protective in two mouse models of cardiac stress-induction, one with isoproterenol overstimulation and the other with 5/6 nephrectomy-induced CKD. Treatment with GCSi does not alter the severity of renal dysfunction and hypertension in CKD. These results provide proof of principle for targeting glucosylceramide synthase to decrease gangliosides as a treatment for cardiac hypertrophy. They also support the hypothesis that sKL protects the heart by targeting gangliosides.

Cardiac metabolic remodelling in chronic kidney disease.

Chronic kidney disease (CKD) affects millions of people globally and, for most patients, the risk of developing cardiovascular disease is higher than that of progression to kidney failure. Moreover, mortality owing to cardiovascular complications in patients with CKD is markedly higher than in matched individuals from the general population. This mortality was traditionally thought to be driven by coronary heart disease but >75% of patients with CKD have left ventricular hypertrophy, which contributes to mortality, particularly sudden cardiac death. The aetiology of cardiac complications in CKD is multifactorial. In addition to haemodynamic overload, uraemic toxin accumulation and altered ion homeostasis, which are known to underlie left ventricular hypertrophy in CKD and drive cardiac dysfunction, we examine the role of myocardial metabolic remodelling in CKD. Uraemic cardiomyopathy is characterized by myriad cardiac metabolic maladaptations, including altered mitochondrial function, changes in myocardial substrate utilization, altered metabolic transporter function and expression, and impaired insulin response and phosphoinositide-3 kinase-AKT signalling, which collectively lead to impaired cardiac energetics. Interestingly, none of the standard treatments used to treat CKD target the metabolism of the uraemic heart directly. An improved understanding of the cardiac metabolic perturbations that occur in CKD might allow the development of novel treatments for uraemic cardiomyopathy.

Npt2a as a target for treating hyperphosphatemia.

Hyperphosphatemia results from an imbalance in phosphate (Pi) homeostasis. In patients with and without reduced kidney function, hyperphosphatemia is associated with cardiovascular complications. The current mainstays in the management of hyperphosphatemia are oral Pi binder and dietary Pi restriction. Although these options are employed in patients with chronic kidney disease (CKD), they seem inadequate to correct elevated plasma Pi levels. In addition, a paradoxical increase in expression of intestinal Pi transporter and uptake may occur. Recently, studies in rodents targeting the renal Na+/Pi cotransporter 2a (Npt2a), responsible for ∼70% of Pi reabsorption, have been proposed as a potential treatment option. Two compounds (PF-06869206 and BAY-767) have been developed which are selective for Npt2a. These Npt2a inhibitors significantly increased urinary Pi excretion consequently lowering plasma Pi and PTH levels. Additionally, increases in urinary excretions of Na+, Cl− and Ca2+ have been observed. Some of these results are also seen in models of reduced kidney function. Responses of FGF23, a phosphaturic hormone that has been linked to the development of left ventricular hypertrophy in CKD, are ambiguous. In this review, we discuss the recent advances on the role of Npt2a inhibition on Pi homeostasis as well as other pleiotropic effects observed with Npt2a inhibition.

Abstract 10293: The Association of Fibroblast Growth Factor-23 with Cardiac Structure and Function in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Fibroblast growth factor-23 (FGF-23), a protein regulating phosphorus levels, is associated with the risk of heart failure, particularly in patients with chronic kidney disease (CKD), and with left ventricular (LV) hypertrophy in CKD. However, few studies have explored this association in the general population, and it is unknown whether FGF23 is associated with other parameters of cardiac structure and function. Methods: Among 5,533 Black or White participants attending Visit 5 (2011-2013) of the community-based ARIC study, we quantified the cross-sectional association of serum FGF-23 levels with echocardiographic measures of cardiac structure and function after accounting for potential confounders including kidney function. Results: Mean age was 76 [SD 5] years, 58 % were women, and 21 % were Black. Among the echocardiographic parameters tested ( Table ), higher FGF-23 levels were robustly associated with LV hypertrophy (adjusted odds ratio [aOR] 1.35 [95%CI 1.02-1.79] in top vs. bottom quartile), abnormal peak longitudinal strain (aOR 1.88 [1.32-2.69]), and left atrial enlargement based on left atrium volume index (aOR 1.34 [1.05-1.70]). No association was observed with E/e’ ratio. Higher FGF-23 was also associated with end-diastolic right ventricular (RV) enlargement (aOR 1.36 [1.04-1.78]). Similar results were observed when echocardiographic measures were modeled as continuous variables and when we stratified participants by demographics (age, sex, and race) or a history of cardiovascular disease. Conclusions: In community-dwelling older adults, in addition to LV hypertrophy, FGF-23 was associated with LV systolic and diastolic function as well as RV size, independent of kidney function and other potential confounders. These findings further support the involvement of FGF-23 in the pathophysiology of cardiac remodeling.

A systematic review and meta-analysis of murine models of uremic cardiomyopathy

Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in "single hit" strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in "multifactorial hit" strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, "multifactorial hit" models more consistently induced cardiac hypertrophy and fibrosis compared to "single hit" kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can "prime" for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.

Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease-A Pediatric Perspective.

Cardiovascular diseases (CVD) are a hallmark in pediatric patients with chronic kidney disease (CKD) contributing to an enhanced risk of all-cause and CV morbidity and mortality in these patients. The bone-derived phosphaturic hormone fibroblast growth factor (FGF) 23 progressively rises with declining kidney function to maintain phosphate homeostasis, with up to 1,000-fold increase in patients with kidney failure requiring dialysis. FGF23 is associated with the development of left ventricular hypertrophy (LVH) and thereby accounts to be a CVD risk factor in CKD. Experimentally, FGF23 directly induces hypertrophic growth of cardiac myocytes in vitro and LVH in vivo. Further, clinical studies in adult CKD have observed cardiotoxicity associated with FGF23. Data regarding prevalence and determinants of FGF23 excess in children with CKD are limited. This review summarizes current data and discusses whether FGF23 may be a key driver of LVH in pediatric CKD.

MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease.

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor–β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.

FGF23 signalling and physiology.

Fibroblast growth factor 23 (FGF23) is a phosphotropic hormone that belongs to a subfamily of endocrine FGFs with evolutionarily conserved functions in worms and fruit flies. FAM20C phosphorylates FGF23 post-translationally, targeting it to proteolysis through subtilisin-like proprotein convertase FURIN, resulting in secretion of FGF23 fragments. O-glycosylation of FGF23 through GALNT3 appears to prevent proteolysis, resulting in secretion of biologically active intact FGF23. In the circulation, FGF23 may undergo further processing by plasminogen activators. Crystal structures show that the ectodomain of the cognate FGF23 receptor FGFR1c binds with the ectodomain of the co-receptor alpha-KLOTHO. The KLOTHO-FGFR1c double heterodimer creates a high-affinity binding site for the FGF23 C-terminus. The topology of FGF23 deviates from that of paracrine FGFs, resulting in poor affinity for heparan sulphate, which may explain why FGF23 diffuses freely in the bone matrix to enter the bloodstream following its secretion by cells of osteoblastic lineage. Intact FGF23 signalling by this canonical pathway activates FRS2/RAS/RAF/MEK/ERK1/2. It reduces serum phosphate by inhibiting 1,25-dihydroxyvitamin D synthesis, suppressing intestinal phosphate absorption, and by downregulating the transporters NPT2a and NPT2c, suppressing phosphate reabsorption in the proximal tubules. The physiological role of FGF23 fragments, which may be inhibitory, remains unclear. Pharmacological and genetic activation of canonical FGF23 signalling causes hypophosphatemic disorders, while its inhibition results in hyperphosphatemic disorders. Non-canonical FGF23 signalling through binding and activation of FGFR3/FGFR4/calcineurin/NFAT in an alpha-KLOTHO-independent fashion mainly occurs at extremely elevated circulating FGF23 levels and may contribute to mortality due to cardiovascular disease and left ventricular hypertrophy in chronic kidney disease.

Left ventricular hypertrophy in chronic kidney disease: A diagnostic criteria comparison

Background and aimsCKD patients have a high prevalence of LVH and this leads to an increase of cardiovascular risk. The aim of this study was to assess the prevalence of left ventricular hypertrophy (LVH) and left ventricular geometry in a group of 293 hypertensive patients with stage 2–5 chronic kidney disease (CKD), compared with 289 essential hypertensive patients with normal renal function. Methods and resultsAll patients underwent echocardiographic examination. Patients on stage 1 CKD, dialysis treatment, or with cardiovascular diseases were excluded. LVH was observed in 62.8% of patients with CKD and in 51.9% of essential hypertensive patients (P < 0.0001). We found increasingly higher left ventricular diameters, thicknesses, and mass from stage 2–5 CKD. Distribution of concentric and eccentric LVH was not very different between the two groups. However, after introducing mixed hypertrophy, the difference between the two groups group was disclosed (P = 0.027). Multiple regression analysis confirmed that the association between renal function and left ventricular mass (β −0.287; P < 0.0001) was independent by potential confounders. Diastolic function was significantly worse in patients with CKD, especially in more advanced stages. ConclusionOur study confirms that LVH is highly prevalent in patients with CKD, especially by using the most recent cut off; in this population, LVH is often characterized by the simultaneous increase of wall thicknesses and diameters with negative effects on diastolic function.

Gender Features of the Prevalence, Development and Progression of Left Ventricle Hypertrophy in Chronic Kidney Disease

Aim of the Study: To study the features of the prevalence of left ventricular hypertrophy in chronic kidney disease, taking into account gender differences. Materials and Methods: This were an instant study. We examined 945 patients (360 female and 585 male) with chronic kidney disease (CKD) from the 1st to the 5th stage of the disease. The average age of the patients was 39.0±13.0 years. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. Results: In patients with female CKD, a significant decrease in hemoglobin, erythrocyte count, and eGFR was detected compared with males, while the incidence of hyperuricemia was significantly higher. Daily proteinuria was significantly higher in men compared with women. The prevalence of LVH was significantly higher in females compared with men (49.4% versus 35.7%; p&lt;0.05). In women and men, the eccentric type prevailed in the structure of LVH. The number of patients with an eccentric type of LVH was significantly higher in the subgroup of females (p&lt;0.05), and with concentric remodeling of the LV were significantly higher in males (p&lt;0.05). Conclusion: The prevalence of LVH among the examined individuals with CKD was 40.9%. Among women, the most common type of LVH was the eccentric type of remodeling (79.2%), and among men, the concentric type of LVH was 39.7% of cases.

Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5.

Background and Aims Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more susceptible to injury and results in cardiovascular calcification and left ventricular hypertrophy in chronic kidney disease. However, the role of α-klotho in acute heart injury and acute kidney injury with sepsis remains unknown. This study aimed to investigate the effects and mechanisms of α-klotho in septic cardiorenal injury. Methods Male 8-week-old C57BL/6 mice were randomly assigned to the control group, lipopolysaccharide (LPS; 10 mg/kg) group, LPS (10 mg/kg)+α-klotho (0.01 mg/kg) group, and LPS (10 mg/kg)+α-klotho (0.02 mg/kg) group. Recombinant α-klotho was intraperitoneally injected an hour before LPS injection. Mice were euthanized at 24 h after LPS injection. The serum troponin, brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels were measured in all groups at 24 h. Biomarkers of mice heart apoptosis, inflammation, oxidative stress, and endoplasmic reticulum stress, such as caspase-3, interleukin 1 (IL-1), reactive oxygen species (ROS), and glucose-regulated protein 78 (GRP78), were also measured. Results α-Klotho was mainly expressed in mice kidneys and was undetectable in the control mice hearts. α-Klotho substantially decreased after LPS injection. In the LPS group, the serum troponin levels significantly increased as early as 6 h (p < 0.05) after LPS injection, while the BNP, NGAL, and creatinine levels significantly increased at 24 h (p < 0.05). Pretreatment with α-klotho significantly ameliorated acute cardiorenal injury. In the LPS+α-klotho (0.01 mg/kg) group, the levels of apoptosis, inflammation, and oxidative stress were decreased, while the level of endoplasmic reticulum stress was elevated. Conclusions α-Klotho significantly alleviates acute cardiorenal injury in LPS-induced septic cardiorenal injury due to the inhibition of apoptosis, inflammation, and oxidation, as well as the regulation of endoplasmic reticulum stress levels.

Nondipping pattern on 24-h ambulatory blood pressure monitoring is associated with left ventricular hypertrophy in chronic kidney disease.

Few studies have assessed the role of 24-h ambulatory blood pressure monitoring (ABPM) in adults with nondialysis chronic kidney disease (CKD). We examined the potential determinants of left ventricular hypertrophy (LVH) and mass index (LVMI) in this population. We carried out a cross-sectional study on 69 stage 3b-5 CKD adults who had ABPM and transthoracic echocardiography performed simultaneously. Hypertension (HT) was defined as 24 h blood pressure (BP) of at least 130/80 mmHg. ABPM parameters considered were BP dipping status, BP load, and the BP night-time/daytime ratio. We performed stepwise backward multivariate linear and logistic regression to assess the determinants of LVH and LVMI. ABPM parameters were considered the main independent variables, whereas HT, angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist use, glomerular filtration rate of less than 30 ml/min/1.72 m, diabetes, smoking, age, sex, hemoglobin, and parathyroid hormone levels were considered covariates. LVH was present in 22 (31.8%) patients. In linear regression analysis, systolic [β=-13.8, 95% confidence interval (CI)=-26.3 to -1.3, P=0.031] and mean (β=-13.5, 95% CI=-25.7 to -1.2, P=0.031) nondipping status was associated with increased LVMI. BP load and night-time/daytime ABPM ratio were not associated with LVMI. In logistic regression analysis, systolic nondipping status (odds ratio=0.27, 95% CI=0.08-0.91, P=0.036) was associated with LVH. Among covariates, estimated glomerular filtration rate of less than 30 ml/min/1.72 m and HT were associated with LVH and increased LVMI. At 1-year follow-up, mean nondipping status on the initial ABPM remained associated significantly with increased LVMI (β=-19.8, 95% CI=-36.6 to -3.0, P=0.022). These data confirm the high incidence of LVH among nonrenal replacement therapy CKD patients and suggest that the nondipping phenomenon on ABPM is associated independently with LVH and increased LVMI in this population.

The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

BackgroundLeft ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear.MethodsData were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height2.7 ≥ 47 g/m2.7 in female and ≥ 50 g/m2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates.ResultsA total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income (P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069–2.063, P = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834–1.584, P = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866–1.748, P = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002–2.158, P = 0.049; > $4500; reference).ConclusionsIn the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.

The sirtuin1 gene associates with left ventricular myocardial hypertrophy and remodeling in two chronic kidney disease cohorts: a longitudinal study.

Oxidative stress and inflammation are major drivers of myocardial hypertrophy in chronic kidney disease (CKD). The silent information regulator gene 1 (Sirt1) is a fundamental mediator of the response to oxidative stress and inflammation and promotes myocardial growth under stress conditions; therefore, it may contribute to myocardial hypertrophy and concentric remodeling of the left ventricle (LV) in CKD. We investigated the cross-sectional and longitudinal relationship between three candidate polymorphisms in the Sirt1 gene and LV parameters in two cohorts of CKD patients including 235 stage G5D patients and 179 stages G1-5 patients, respectively. In both cohorts, the C allele of the Sirt1 rs7069102 polymorphism associated with the posterior wall thickness in separate and combined analyses (beta = 0.15, P = 2 × 10) but was unrelated with the LV volume and the LV mass index indicating a peculiar association of this allele with LV concentric remodeling. Accordingly, the same allele was linked with the LV mass-to-volume ratio in separate and combined (beta = 0.14, P = 2 × 10) analyses in the same cohorts. Furthermore, in longitudinal analyses patients harboring the C allele showed a more pronounced increase in LV mass-to-volume ratio over time than patients without such an allele (regression coefficient = 0.14, 95% confidence interval: 0.05-0.23; P = 3 × 10 in the combined analysis). The rs7069102 polymorphism in the Sirt1 gene is associated with LV concentric remodeling in two independent cohorts of stages G5D and G1-5 CKD patients. These results offer a genetic basis to the hypothesis that the Sirt1 gene plays a causal role in myocardial hypertrophy and LV concentric remodeling in these patients.

Renal denervation decreases susceptibility of the heart to ventricular fibrillation in a canine model of chronic kidney disease.

What is the central question of this study? Renal denervation (RDN) has been shown to be effective and safe, resulting in better control of blood pressure and an improvement in left ventricular hypertrophy in chronic kidney disease (CKD) patients. Ventricular arrhythmias and sudden cardiac death are common causes of death in CKD patients, but previous studies pay almost no attention to the effects of RDN on the risk of ventricular fibrillation associated with CKD. What is the main finding and its importance? Renal denervation could decrease susceptibility of the heart to ventricular fibrillation in a canine CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects. Renal denervation (RDN) has been shown to have therapeutic value in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether RDN could decrease the susceptibility of the heart to ventricular fibrillation in a canine model of CKD. Twenty-one dogs were used. Chronic kidney disease was produced by subtotal nephrectomy in 16 dogs with RDN treatment (CKD+RDN group, n=8) or sham RDN (CKD group, n=8). Another five dogs underwent sham operation and sham RDN to serve as controls (CTR group). Parameters of renal function, blood pressure, echocardiography, ECG, noradrenaline and inflammation were measured at baseline and 6weeks after the surgical procedure. The ventricular fibrillation threshold (VFT) was determined at the end of the study. Subtotal nephrectomy successfully induced a canine CKD model. When compared with the CTR group, subtotal nephrectomy in the CKD group significantly elevated blood pressure; increased the left ventricular mass, end-diastolic left ventricular internal dimension, left ventricular end-diastolic posterior wall thickness and end-diastolic interventricular septum thickness; prolonged the QT interval, corrected QT interval, the interval from the peak to the end of the T wave (Tp-e) and the corrected Tp-e interval; and increased the QT dispersion and the Tp-e/QT ratio; decreased the VFT; and increased the serum concentrations of noradrenaline, C-reactive protein and interleukin-6. Renal denervation significantly attenuated these changes induced by CKD. The study demonstrated that RDN could decrease the susceptibility of the heart to ventricular fibrillation in this CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects.