Patients with chronic kidney disease (CKD) exhibit an elevated cardiovascular risk manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Although the inciden...

Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options.

Cardiovascular disease (CVD) is a highly common complication and the first cause of death in patients with end-stage renal disease (ESRD) on haemodialysis (HD). In this population, mortality due to CVD is 20 times higher than in the general population and the majority of maintenance HD patients have CVD. This is likely due to ventricular hypertrophy as well as non-traditional risk factors, such as chronic volume overload, anaemia, inflammation, oxidative stress, chronic kidney disease-mineral bone disorder and other aspects of the 'uraemic milieu'. Better understanding the impact of these numerous factors on CVD would be an important step for prevention and treatment. In this review we focus non-traditional CVD risk factors in HD patients.

Cardiovascular disease in dialysis patients.

Background - Patients with end-stage renal disease are at high risk for cardiovascular morbidity and mortality. The aims of the present study were to describe the prevalence of peripheral arterial disease ( PAD) and its effects on prognosis and health-related quality of life ( HRQOL) in an international cohort of patients on hemodialysis. Methods and Results - Data from the Dialysis Outcomes and Practice Patterns Study ( DOPPS), a prospective, international, observational study of hemodialysis patients ( n = 29 873), were analyzed. Associations between baseline clinical variables and PAD were evaluated by logistic regression analysis. Cox regression models were used to test the association between PAD and risk for all-cause mortality, cardiac mortality, and hospitalization. PAD was diagnosed in 7411 patients ( 25.3%) with significant geographic variation. Traditional cardiovascular risk factors including age, male sex, diabetes, hypertension, and smoking were identified, together with the duration of hemodialysis, as significant correlates of PAD. Diagnosis of PAD was associated with increased all-cause mortality ( hazard ratio [ HR] = 1.36; P < 0.0001), cardiac mortality ( HR = 1.43; P < 0.0001), all-cause hospitalization ( HR = 1.19; P < 0.0001), and hospitalization for a major adverse cardiovascular event ( HR = 2.05; P < 0.0001). HRQOL questionnaires revealed physical health scores that were significantly lower in PAD compared with non-PAD patients ( P < 0.0001). Conclusions - PAD is common in hemodialysis patients and is associated with increased risk of cardiovascular mortality, morbidity, and hospitalization and reduced HRQOL.

Peripheral arterial disease in patients with end-stage renal disease - Observations from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD–mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters

Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.

Atherosclerosis in Chronic Kidney Disease: More, Less, or Just Different?

Vascular calcification is a risk factor for the pathogenesis of cardiovascular disease and mortality in dialysis patients. Nevertheless, the association between cardiac valve calcification (CVC) and the outcome of dialysis is still illusive. The purpose of this meta-analysis is to evaluate the association between theCVC and cardiovascular or all-cause mortality in dialysis patients. Literatures involving the baseline CVC and cardiovascular or all-cause mortality in dialysis patients were searchedfrom the PubMed, Embase, as well as two Chinese databases (i.e. Wanfang and CNKI databases). Articles published before November 2016were eligible to the study. Ten studies involving 2686 participants were included. CVC was correlated with increased risk of cardiovascular mortality (hazard risk [HR]: 2.81; 95% confidence intervals [CI]: 1.92–4.10) and all-cause mortality (HR: 1.73; 95% CI: 1.42–2.11). Subgroup analysis showed an excess risk of all-cause mortality (HR: 1.35; 95% CI: 1.02–1.79) among patients with one CVC, and increased risk of all-cause mortality in patients with two CVCs (HR 2.15; 95% CI 1.57–2.94). CVC is correlated with higher cardiovascular and all-cause mortality risk in dialysis patients. Regular follow-up monitoring of CVC may be helpful for risk stratification of patients underwent dialysis.

/pdf/cardiac-valve-calcification-and-risk-of-cardiovascular-or-50sxp73oqu.pdf

Cardiac valve calcification and risk of cardiovascular or all-cause mortality in dialysis patients: a meta-analysis.

Aim

An arteriovenous fistulae (AVF) is the preferred vascular access for maintenance haemodialysis patients. Its dysfunction is often due to venous stenosis, which is mainly caused by neointimal hyperplasia. Additionally, haemodynamic forces, especially wall shear stress (WSS), as a mechanical stimuli to venous wall have a significant role in neointimal hyperplasia. The purpose of this study was to evaluate the association between WSS and neointimal hyperplasia.



Methods

An ‘end-to-side’ AVF was created between the right femoral artery and vein of canines. Canines were killed at 7 and 28 days post-surgery. The velocity and WSS in the three-dimensional computational model of AVF were simulated using computational fluid dynamics (CFDs). The four typical sites of the vein evaluated in this study, chosen according to the haemodynamic analysis, included the arteriovenous anastomosis (A-V), the juxta-anastomotic segment (J-V), the juxta-ligation segment (L-V) and the proximal vein (P-V). The specimens were haematoxylin-eosin stained and the intima-media thickening was then measured.



Results

Neointimal hyperplasia was more obvious in the inner wall of the J-V and L-V (low-and-disturbed WSS) sites compared with the P-V and A-V sites, and the outer wall of the L-V and J-V segments (high or laminar WSS) (P < 0.01).



Conclusion

In this study, we described the haemodynamic condition in the AVF and found that neointimal hyperplasia predisposed to occur in the inner wall of venous segment near the anastomosis. We also found that not only the neointimal hyperplasia has a strong inverse correlation with WSS levels, but also is related to flow patterns.

Effects of wall shear stress in venous neointimal hyperplasia of arteriovenous fistulae

Prognostic role of ankle-brachial index (ABI) in patients with chronic kidney disease (CKD) is controversial. We aimed to evaluate whether abnormal ABI was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by conducting a meta-analysis. We systematically searched Pubmed and Embase databases for prospective observational studies that investigated baseline abnormal ABI and subsequent cardiovascular or all-cause mortality risk in CKD patients with or without hemodialysis. An ABI value of 0.9 to 1.3 was defined as normal. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the abnormal vs. normal ABI category. Six studies enrolling 5820 patients were identified and analyzed. Overall, abnormal ABI was associated with an increased risk of all-cause mortality (HR 2.26; 95% CI 1.60-3.18) and cardiovascular mortality (HR 3.58; 95% CI 2.53-5.06). Subgroup analysis indicated that patients with abnormally low ABI increased by 2.45-fold all-cause mortality and 5.18-fold cardiovascular mortality. Similarly, an abnormally high ABI increased by 1.94-fold all-cause mortality and 4.04-fold cardiovascular mortality. In addition, the effect of abnormal ABI on all-cause mortality was more pronounced among hemodialysis patients (HR 3.06; 95% CI 2.30-4.07) but not in CKD patients (HR 1.42; 95% CI 0.98-2.05). Abnormally low and high ABI are independently associated with cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. This meta-analysis highlighted an U-shaped relationship between ABI and mortality risk in CKD patients undergoing hemodialysis. However, findings of this meta-analysis were undermined by the small number of included studies.

Abnormal ankle-brachial index and risk of cardiovascular or all-cause mortality in patients with chronic kidney disease: a meta-analysis.

Background: Many studies have suggested a correlation between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and diabetic nephropathy (DN), but their results are inconclusive. Methods: To confirm this correlation, we performed a meta-analysis of 15 studies. The dichotomous data are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: The results of this study suggested that the MTHFR 677 T allele was more likely to increase the risk of DN in Asian (OR = 1.466, 95% CI = 1.143-1.880, P = 0.003), West Asian (OR = 1.750, 95% CI = 1.150-2.664, P = 0.009), and Chinese populations (OR = 2.162, 95% CI = 1.719-2.719, P = 0.001), but not in East Asian or Japanese populations. The carriers of the MTHFR 677 T allele were associated with progression of DN in the “5-10 year duration” group, but not in the “> 10 year duration” group (OR = 2.187, 95% CI = 1.787-2.677, P = 0.001). Conclusion: Development of DN is associated with MTHFR C677T polymorphisms in Asian populations, especially in early type 2 diabetes.

MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis.

Hemodynamic forces have an important role in venous intimal hyperplasia, which is the main cause of arteriovenous fistula dysfunction. Endothelial cells (ECs) constantly exposed to the shear stress...

Aili Jiang

Papers

Cardiac valve calcification and risk of cardiovascular or all-cause mortality in dialysis patients: a meta-analysis.

Effects of wall shear stress in venous neointimal hyperplasia of arteriovenous fistulae

Abnormal ankle-brachial index and risk of cardiovascular or all-cause mortality in patients with chronic kidney disease: a meta-analysis.

MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis.

Effects of Caveolin-1-ERK1/2 pathway on endothelial cells and smooth muscle cells under shear stress: