Cardiovascular Disease In Chronic Kidney Disease Patients Research Articles

Cardiovascular Functional Changes in Chronic Kidney Disease: Integrative Physiology, Pathophysiology and Applications of Cardiopulmonary Exercise Testing.

The development of cardiovascular disease during renal impairment involves striking multi-tiered, multi-dimensional complex alterations encompassing the entire oxygen transport system. Complex interactions between target organ systems involving alterations of the heart, vascular, musculoskeletal and respiratory systems occur in Chronic Kidney Disease (CKD) and collectively contribute to impairment of cardiovascular function. These systemic changes have challenged our diagnostic and therapeutic efforts, particularly given that imaging cardiac structure at rest, rather than ascertainment under the stress of exercise, may not accurately reflect the risk of premature death in CKD. The multi-systemic nature of cardiovascular disease in CKD patients provides strong rationale for an integrated approach to the assessment of cardiovascular alterations in this population. State-of-the-art cardiopulmonary exercise testing (CPET) is a powerful, dynamic technology that enables the global assessment of cardiovascular functional alterations and reflects the integrative exercise response and complex machinery that form the oxygen transport system. CPET provides a wealth of data from a single assessment with mechanistic, physiological and prognostic utility. It is an underutilized technology in the care of patients with kidney disease with the potential to help advance the field of cardio-nephrology. This article reviews the integrative physiology and pathophysiology of cardio-renal impairment, critical new insights derived from CPET technology, and contemporary evidence for potential applications of CPET technology in patients with kidney disease.

Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease.

Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD). Reduced nitric oxide (NO) bioavailability has been associated with increased CVD in CKD patients. Children tend to have more exposure to acrylamide, one of the most common toxins in food. We aimed to determine whether urinary levels of acrylamide metabolites N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) are associated with CV risk markers in children with CKD. Data on 112 children and adolescents ages three to 18 years old with CKD stage G1–G4 are reported. We observed that 24 h ambulatory blood pressure monitoring (ABPM) abnormalities were greater, and left ventricular (LV) mass and ambulatory arterial stiffness index (AASI) were higher in children with CKD stage G2–G4 versus G1. Patients with CKD stage G2–G4 had a lower urinary acrylamide level, but a higher AAMA-to-GAMA ratio than those with CKD stage G1. Urinary acrylamide level was negatively associated with high systolic blood pressure (SBP) and diastolic BP (DBP) load on 24 h ABPM. Lower urinary levels of acrylamide, AAMA, and GAMA were correlated with LV mass. Additionally, GAMA are superior to AAMA related to NO-related parameters, namely citrulline and symmetric dimethylarginine (SDMA). This study suggests that determinations of urinary acrylamide level and its metabolites in the early stages of pediatric CKD may identify patients at risk of CVD. Further studies should clarify mechanisms underlying acrylamide exposure to define the treatment for protection against CVD.

P1134HIGH PREVALENCE OF SLEEP-DISODERED BREATHING AND ITS ASSOCIATION WITH RENAL FUNCTION AMONG CHRONIC KIDNEY DISEASE PATIENTS (CKD1-5,HD AND PD) : A CROSS-SECTIONAL STUDY

Abstract Background and Aims Sleep-disordered breathing (SDB) is known as a novel risk factor for cardiovascular disease, and one of five adults suffer from SDB in general population. In non-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, a high prevalence of SDB has been reported due to the excess accumulation of extracellular fluid. However, precise prevalence and associated factors of SDB in patients with peritoneal dialysis (PD) has not been known. This cross-sectional study aimed to investigate the prevalence and determinant factors associated with SDB in patients with CKD. Method This was a single-center retrospective cohort study recruited 334 patients with CKD stages 1-3a, 3b-5, HD, and PD enrolled from 2018 to 2020. All patients were hospitalized and received our CKD educational program, and did not have sleep complaints. The diagnosis and assessment of the severity of SDB were evaluated using PULSOX-Me300 and SAS2100 systems. The 3% oxygen desaturation index and SpO2 were measured during sleep. SDB was defined as 3% oxygen desaturation index (ODI)>15.0 and SpO2<92% in this study. Results Proportion of the patients with CKD1-3a, CKD3b-5, HD, and PD were 28%, 53%, 11%, and 8%, respectively. Thirty-one% of the patients were diagnosed with SBD in all CKD patients. In a generalized linear model, 3% ODI>15.0 and SpO2<92% were significantly correlated with apnea hypopnea index (p<0.05, r=0.87 and p<0.05, r=-0.45, respectively). Further, it became clear that the proportion of 3%ODI>15 and SpO2<92% was significantly higher in PD patients (50%) than in other CKD patients. Furthermore, 3% ODI was significantly correlated with BMI and HDL cholesterol levels in PD patients (p<0.05, r=0.67 and p<0.05, r=-0.54, respectively). Conclusion We reported for the first time that the prevalence of SDB was very high and that the severity of SDB was significantly associated with BMI in patients with PD. These findings suggest that the extracellular fluid overload and excess glucose exposure due to PD fluid might accelerate SDB in patients with PD. Further clinical studies are needed to determine whether PD-associated SDB might influence the development of cardiovascular disease in CKD patients.

Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux

Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction.

Trimethylamine-N-oxide and cardiovascular events in chronic kidney disease

Trimethylamine-N-oxide (TMAO) is a biologically active molecule which is metabolized by intestinal microflora and excreted by the kidney. The incidence and mortality of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) are significantly increased, which seriously affects the prognosis of patients with CKD. Recent studies have shown that TMAO can cause myocardial fibrosis and cardiovascular damage. Plasma TMAO levels are elevated in CKD patients, and TMAO was an independent predictor for all-cause mortality in patients with CKD, including CVD events. As a "uremic toxin", TMAO can promote the progression and the occurrence of CVD in CKD patients through its toxic effects, such as inflammatory response and oxidative stress. Taken together, it may suggest that reducing TMAO production and plasma TMAO levels may decrease the occurrence of CVD events in CKD and that TMAO may be a therapeutic target for ameliorating the prognosis of CKD.

The impact of dyslipidemia and oxidative stress on vasoactive mediators in patients with renal dysfunction.

Hyperlipidemia and oxidative stress are indispensable features of chronic kidney disease (CKD) that favor the development of atherogenic plaques and cardiovascular disease (CVD). A number of vasoactive mediators including proprotein convertase subtilisin-kexin type 9 (PCSK9), endothelin-1, nitric oxide, and angiotensin II have fundamental roles in the pathophysiology of atherosclerotic events; moreover, their levels are affected by dyslipidemia and oxidative stress due to renal dysfunction. Therefore, therapeutic measures aimed at correcting dyslipidemia and alleviating oxidative stress could potentially protect against CVD in CKD patients. In this review, we discuss the relation between dyslipidemia, oxidative stress, and vasoactive mediators as well as the available treatment options against these disturbances in CKD patients.

SUN-193 GDF-15, Hepcidin, and Iron deficiency Anaemia as Predictors of Disease Progression and Mortality in CKD Patients

Anaemia is one of the common complications of Chronic Kidney Disease (CKD) that has been strongly associated with adverse clinical outcomes. An interplay between emerging biomarkers of inflammation and anaemia has been shown to play a vital role in the increased risk of cardiovascular disease in CKD patients. This association may partly be responsible for the persistent increased risk of mortality despite correction of anaemia in CKD patients.

A study of lipid profile in chronic kidney disease in pre- dialysis patients

Introduction: Longitudinal studies have established that Cardiovascular Disease (CVD) occur more frequently and are the leading cause of death in Chronic Kidney Disease (CKD). Dyslipidemia has been established as an important risk factor in the pathogenesis of CVD in CKD patients. Objectives: Present study was aimed to evaluate (in CKD patients),Demography along with Prevalence and Pattern of Dyslipidemiaand co-relation of Dyslipidemia with various CK Dstages. Methods: Present Cross-sectional study, conducted in Department of Medicine, R.D. Gardi Medical College and CRG hospital, Ujjain, M.P. from 1st January 2015 to 31st July 2016.We studied 115 pre-dialysis CKDcases and 100 age & sex matched controls. CKD was diagnosed as per 2012 KDOQI Criteria. Result:In CKD cases,maximum 23.47% cases belonged to fifth decade. Mean age was 48.99 ± 16.74. Male to Female ratio was1.21: 1. Prevalence of individual dyslipidemias was High TC= 50.44%, High TG= 67%, High LDL-C= 42%, High VLDL-C= 67% and Low HDL-C= 73.9%. Overall, prevalence of dyslipidemia was 82.6%. Significant increase in TG and VLDL-C and significant decrease in HDL-C was observed. TC and LDL-C were non- significantly increased.TC, TG, LDL-C and VLDL-C were in increasing trend with progression of CKD stages (3-5) and increased in Subgroup II (ESRD) as compared to Subgroup I (Non-ESRD), the increase being significant in case of TG and VLDL-C. HDL-C value was in decreasing trend with progression of CKD stages and significantly decreased in Subgroup II as compared to Subgroup I.TC, TG, LDL-C and VLDL-C showed negative correlation with GFR while HDL-C showed positive correlation. TG, HDL-C and VLDL-C showed highly significant correlation. HDL-C showed strongest correlation, followed by TG. Conclusion: Patients with CKD are predisposed to accelerated atherosclerosis leading to increased CVD. This study confirms the presence of atherogenic lipid profile in CKD.

The Key Role of Phosphate on Vascular Calcification.

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

Evaluation of Single-Nucleotide Polymorphisms of Transcription Factor 7-Like 2 and ATP2B1 Genes as Cardiovascular Risk Predictors in Chronic Kidney Disease.

Introduction:Cardiovascular disease (CVD) is the primary cause of morbidity and premature mortality in chronic kidney disease (CKD). The transcription factor 7-like 2 (TCF7L2) gene product TCF4 is a transcription factor that acts as a downstream effector in the canonical Wnt signaling pathway and may be important in the development of both type 2 diabetes and renal development and disease. It is, therefore, plausible that mutations in this gene could manifest themselves in reduced kidney function or kidney disease through their effects on hyperglycemia as well as independent of this mechanism. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which removes bivalent calcium ions from eukaryotic cells against very large concentration gradients and is responsible for controlling the contraction and dilation of vascular smooth muscles.Aim and Objectives:The aims of this study are (1) to evaluate single-nucleotide polymorphisms (SNPs) of TCF7L2 gene as cardiovascular risk predictors in CKD and (2) to evaluate SNPs of ATP2B1 gene as cardiovascular risk predictors in CKD.Subjects and Methods:Fifty clinically diagnosed CKD patients in the age group between 20 and 60 years of both genders were selected as cases and fifty healthy participants from the master health checkup department were selected as controls. Genomic DNA was extracted based on the spin column kit method. The DNA samples were stored at −20°C until analysis. Genotyping for TCF7L2 gene rs7903146 (C/T) and ATP2B1 gene rs11105354 (A/G) was carried out through polymerase chain reaction.Results:T allele frequency was observed in 12 controls and 23 cases (odds ratio [OR] = 2.2, 95% confidence interval [CI]: 1.0–4.7). CC genotype was observed in 38 controls and 27 cases and CT genotype in 22 cases and 12 controls. A allele was found in 38 cases and 23 controls (OR = 2, 95% CI: 1.1–3.8). The mean values of cholesterol, low-density lipoprotein, triglycerides, glucose, insulin, urea, and creatinine were high in cases when compared to controls.Conclusion:T allele of TCF7L2 gene rs7903146 (C/T) and A allele of ATP2B1 (A/G) gene rs11105354 (A/G) are associated with CVD in CKD patients.

Novel aspects of PCSK9 and lipoprotein receptors in renal disease-related dyslipidemia

Chronic kidney disease (CKD) is a global health problem with a profound impact on quality of life. Cardiovascular disease is established as a major cause of morbidity and mortality in patients with CKD. Dyslipidemia is frequently observed in CKD patients, suggesting a causal relation between dyslipidemia and cardiovascular disease in CKD patients. Currently, lipid-lowering drugs such as statins, are the primary choice for lipid lowering therapy in high-risk populations. Despite many studies showing CVD risk reduction with statins, CVD still remains the leading cause of the death in CKD. This underscores the need for new therapeutic approaches to reduce cardiovascular risk in CKD patients. Reduced lipoprotein lipase activity, increased very low-density lipoprotein production, increased proprotein convertase subtilisin kexin type 9 (PCSK9) expression and loss of hepatic heparan sulfate proteoglycans (HSPG) syndecan-1 have been associated with CKD-related dyslipidemia. Low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor-related protein 1 (LRP-1) and syndecan-1, are the most important hepatic receptors for lipoprotein clearance. However, their contributions to the pathogenesis of dyslipidemia and cardiovascular disease in CKD remain unclear. Interestingly, in CKD, increased plasma lipid levels are associated with elevated levels of PCSK9. This promotes the proteolysis of LDLR, suggesting a role for PCSK9 in CKD-associated dyslipidemia. Fully humanized monoclonal antibodies targeting PCSK9 have been approved by the US Food and Drug Administration and the European Medicines Agency as lipid lowering treatment for patients with hypercholesterolemia. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated strong reduction in LDL-C by alirocumab compared to placebo and ezetimibe and when added to statins. However, their efficacy in reducing plasma TG is controversial. Therefore, further research work is need for a detailed analysis on efficacy and safety of PCSK9 antibodies in CKD groups. Interestingly, novel findings on PCSK9 interaction with HSPG might shed new insight on altered lipid metabolism in CKD. In this review, we discuss various aspects of lipoprotein metabolism and hepatic lipoprotein receptor signaling pathways along with the concept of renal disease-related dyslipidemia. Furthermore, this review highlights the drawbacks of current lipid-lowering therapies and proposes novel approaches for lipid management in CKD.

Cardiovascular Screening and Early Detection of Heart Disease in Adults With Chronic Kidney Disease

Abstract Cardiovascular disease (CVD) and chronic kidney disease (CKD) are among the most common disease states that nurse practitioners encounter in various health care settings. In many cases, patients with CVD and CKD have overlapping risk factors and underlying medical conditions. CVD is one of the most common causes of death in patients with CKD, and therefore, appropriate recognition and screening are important for preventing disease progression and complications. Nurse practitioners can become familiar with various risk factors, screen patients, and provide nonpharmacologic and pharmacologic measures for CVD in CKD patients.

Management of Blood Pressure and Heart Rate in Chronic Kidney Disease.

Hypertension is considered a major health problem in patients with chronic kidney disease (CKD) as approximately 80-85% of CKD patients' suffer from hypertension in the United States. Hypertension is the second leading cause of CKD after diabetes and is strongly related to morbidity and mortality. It has been found that there is a relation among hypertension, glomerular filtration rate (GFR) and creatinine levels. Since there is a strong relation between hypertension and CKD, and hypertension seems to lead to cardiovascular diseases, which have epidemic proportions in CKD, this review article discusses the etiology of hypertension and the existing optimal therapies that contribute to the hypertension and heart rate management. There are many approaches that contribute to the management of hypertension and heart rate in CKD patients. Lifestyle modifications in combination with drug therapy lead to the better control of hypertension in CKD patients. Hypertension is strongly related to cardiovascular diseases in CKD patients. Since this relation exists and hypertension leads to cardiovascular diseases, the management of hypertension and increased heart rate should be a main therapeutic target in these patients.

Strategies to manage cardiovascular risk in chronic kidney disease.

Cardiovascular disease (CVD) remains the leading cause of death across the spectrum of chronic kidney disease (CKD), including CKD not requiring dialysis and for patients requiring dialysis or kidney transplantation. There is a high prevalence of ‘conventional’ cardiovascular risk factors in patients with CKD such as hypertension, dyslipidaemia, diabetes mellitus, smoking, low physical activity/obesity and prior cardiovascular events. Many risk factors contribute to the aetiology and pathogenesis of CKD or are shared risk factors for CKD progression [1]. Furthermore, there are contributors to accelerated CVD specific to, or exaggerated in CKD. Examples include left ventricular hypertrophy (LVH), fluid and electrolyte shifts, proteinuria, functional vitamin D deficiency, hyperphosphataemia, chronic inflammation, vascular stiffness and/or vascular calcification. There are multiple other putative mechanisms for accelerated CVD in CKD patients, identified by phenotyping using state of the art imaging, physiological studies and molecular biology, although these are yet to translate to clinical practice. This NDT Digest will discuss the current clinical evidence for addressing CVD risk in CKD.

Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2 Cardiomyoblasts

Background/Aim: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. Methods: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract. FITC-annexin V staining was performed to quantify the apoptotic cells in all groups. Results: Hyperphosphate treatments showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis-associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting. Conclusion: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would lead to cellular apoptosis via autophagy, which is mediated by the pAMPK signaling pathway. Our findings revealed the possible mechanism responsible for the heart damage under hyperphosphatemia.

OP.1A.02] INNATE IMMUNITY AND CARDIO-RENAL RISK IN STAGE 2-5 CKD PATIENTS

Objective: The soluble form of urokinase-type plasminogen activator (suPAR) is a powerful marker for immune activation that accurately predict clinical outcomes in patients with sepsis or infectious diseases. Alterations in innate immunity and Inflammation are major risk factors for the high risk for cardiovascular disease in patients with chronic kidney disease (CKD) but whether suPAR predicts cardiovascular and renal complications independently of established risk factors in CKD is still unknown. Design and method: We measured plasma suPAR levels (ELISA) and a series of traditional and CKD-specific risk factors in 753 stage G2-5 CKD patients. We estimated the risk for GFR loss (>30%) or kidney failure, time to death and first cardiovascular event by multivariate Cox regression analysis adjusting for traditional risk factors and a large series of CKD-specific risk factors. Results: suPAR was gender-dependent and associated with lower GFR and higher proteinuria, older age, diabetes, higher systolic BP, C Reactive Protein (CRP), phosphate, PTH, FGF23, ADMA and lower Hb, 25OH vitD and 1,25OH2 vitD (all P < 0.001). Over a 31 +/− 10 months follow-up 42 patients died and 95 had a renal event. suPAR was a strong predictor of the combined end-point death and cardiovascular events [HR (500pg/ml): 1.09, 95%CI: 1.04–1.14] in a Cox's regression analysis adjusting for a large series of potential confounders including background cardiovascular disease, the GFR, proteinuria, age, gender, smoking, diabetes, systolic BP and anti-hypertensive treatment, phosphate, Hb, serum albumin, BMI, CRP, ADMA and FGF23. Separate analyses of time to death and time to first CV event were both highly significant (P < 0.01) in crude and adjusted analyses. Conclusions: Elevated suPAR levels robustly predict incident cardiovascular events and death in CKD patients. These findings go along with biological knowledge documenting a strong role of suPAR in atherosclerosis and support the contention that suPAR is causally implicated in cardiovascular disease in CKD patients.

Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease.

Cardiovascular disease (CVD) is the main public health problem in patients with chronic kidney disease (CKD); however, there is no established biomarker for predicting CVD morbidity and mortality in CKD. The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in predicting CVD risk in CKD patients.We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001 for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR, r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P = .016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.

Vasculopathy in the setting of cardiorenal syndrome: roles of protein-bound uremic toxins.

Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), while CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neurohormonal, mechanical, and biochemical factors, nondialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo, and clinical observations. PBUTs are ineffectively removed by hemodialysis because their complexes with albumins are larger than the pores of the dialysis membranes. PBUTs such as indoxyl sulfate and p-cresyl sulfate are key determinate and predictive factors for the progression of CVD in CKD patients. In CRS, both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) exhibit significant dysfunction that is associated with the progression of CVD. PBUTs influence proliferation, calcification, senescence, migration, inflammation, and oxidative stress in VSMCs and ECs through various mechanisms. These pathological changes lead to arterial remodeling, stiffness, and atherosclerosis and thus reduce heart perfusion and impair left ventricular function, aggravating CRS. There is limited literature about the effect of PBUT on the vascular system and their contribution to CRS. This review summarizes current knowledge on how PBUTs influence vasculature, clarifies the relationship between uremic toxin-related vascular disease and CRS, and highlights the potential therapeutic strategies of uremic vasculopathy in the setting of CRS.

Prevalence of anemia and cardiovascular diseases in chronic kidney disease patients: a single tertiary care centre study

Background: Chronic kidney disease (CKD) is recognized as a global health issue having high mortality and morbidity rates putting a substantial burden on global resources. CKD has become a recognised independent risk factor for several adverse health outcomes including cardiovascular disease (CVD). Anaemia is an anticipated consequence as renal function declines, and can develop at any stage of CKD. There is a strong association between anemia and cardiovascular complications in CKD patients and many studies have proven that anemia plays a key role in worsening CVD in CKD patients. The objective of this study was to study the prevalence of anemia and cardiovascular diseases in CKD patients and establish an association between them.Methods: This study was conducted between January 2008 and June 2008 for a period of six months at a Government tertiary referral institution in south India. During this period, all newly diagnosed cases of chronic kidney disease based on the National Kidney foundation definition were included in this study. All the patients were evaluated based on detailed history taking, clinical examination and laboratory investigations after an informed consent was obtained from them. Staging of CKD was done based on the national kidney foundation (NKF/KDIGO) staging system. GFR was estimated using the abbreviated MDRD (Modification of Diet in Renal Disease) formula.Results: Of the 333 newly diagnosed CKD patients, a large majority (264, 79.28%) of the patients in the study presented in stage 5 CKD. The mean Hb in the study was 8.42±2.20 g/dl. Anemia was present in 90.39% while 25.53% had an Hb of &lt;7g/dl. The prevalence of anemia increased from stage 3 (66.6%) to stage 5 (94.7%) and this correlation was statistically significant (p&lt;0.0005). 167 (50.15% ) were found to have some form of cardiovascular disease, of which 120 (71.86%) were males and 47 (28.14%) were females. 83.93% had left ventricular hypertrophy, 16.17% had ischemic heart disease and 7.78% had congestive heart failure. 56.3% of patients in the age group 41-60 years had cardiovascular disease. The correlation between cardiovascular disease and age was statistically significant (p = 0.04139). And it was found that cardiovascular disease was more common when the cause of CKD was Diabetic nephropathy (65.8%) and hypertensive nephrosclerosis (84.6%). The correlation between the cardiovascular disease and etiological diagnosis of CKD was statistically significant. (p&lt;0.0005).Cardiovascular disease was present in 61.2 % of the study population with diabetes mellitus and in 56.4% of the study population with hypertension. The correlations between CVD and diabetes and hypertension were statistically significant. Cardiovascular disease was present in 61.2% of the study population with Hemoglobin &lt;7 gm/dl, 41.7% with Hb between 7-11 gm/dl and the correlation between cardiovascular disease and the level of Hb was highly significant in CKD patients.Conclusions: Thus there is a strong association between the clinical trial of anemia, CKD and CVD and prompt identification and management of common risk factors and adequate correction of anemia is necessary to slow progression of CKD and prevent cardiovascular events.

Could physical exercise help modulate the gut microbiota in chronic kidney disease?

Chronic kidney disease (CKD) patients have several metabolic disorders caused by chronic oxidative stress and inflammation. The imbalance of gut microbiota has been identified as a factor that may contribute to the development of these disorders, which can promote cardiovascular disease in CKD patients. Among several strategies to modulate gut microbiota, physical exercise could represent a new nonpharmacological approach. Although exercise can reduce cardiovascular risk in CKD patients through its beneficial effects on oxidative stress and inflammation, there are no available data regarding the relationship between exercise and modulation of gut microbiota in CKD patients. This review is intended to provide a brief overview of the hypothesis regarding gut microbiota modulation through physical exercise, with a particular emphasis on CKD.