Chronic kidney disease and cardiovascular disease: what came first, the chicken or the egg?

A Decade After the KDOQI CKD Guidelines: Impact on the United States and Global Public Policy

Prevalence of chronic kidney disease and anemia among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study: Baseline results

Objective A new view is proposed for the mechanism of exercise prevention and improvement of chronic disease, that exercise may play a role by promoting the expression of anti-aging protein α-Klotho.
 Methods By means of literature review and prospective analysis, this paper summarizes the research status of the application of exercise in the prevention and improvement of chronic diseases and the effects of anti-aging protein α-Klotho on chronic cardiovascular disease, diabetes, chronic kidney disease and cancer and other chronic diseases and the effect of exercise on the expression of plasma α-Klotho and its possible mechanism. The research prospects of exercise to interfere with chronic diseases by promoting the expression of α-Klotho are envisioned
 Results (1) At present, the incidence and mortality of chronic diseases are high on a global scale. With the development of aging, chronic diseases will cause a serious economic burden and great waste of resources. Therefore, research on how to prevent and treat chronic diseases related to aging and lifestyle has become a top priority. Strong evidence suggests that exercise is an economical and efficient way to slow down the progress of some chronic diseases and to control symptoms such as diabetes, chronic kidney disease, heart failure, cardiovascular disease, and so on. However, we have not fully understood the cellular and molecular mechanisms underlying the effects of exercise.(2) α-Klotho is an anti-aging protein that regulates calcium and phosphorus metabolism, inhibits Wnt signaling, inhibits oxidative stress, and inhibits tumor and fibrosis. It has been proved to play an important role in the occurrence and development of chronic diseases such as chronic cardiovascular disease, diabetes, chronic kidney disease, tumor and other chronic diseases.(3) Exercise has been proved to be effective in promoting the expression of plasma α-Klotho protein, and the degree of response may be related to physical fitness and age. However, the mechanism of exercise to promote the expression of α-Klotho protein has not been reported. Combined with the existing research results, it is presumed that it may be related to DNA methylation, Peroxisome proliferator-activated receptor gamma(PPARγ) signal transduction and vitamin D receptor. 
 Conclusions Exercise has gradually become an important way to intervene in chronic diseases, but the lack of understanding of its mechanism hinders the development of exercise in the field of prevention and treatment of chronic diseases. It is found that exercise can promote the expression of plasma α-Klotho protein, and the expression of α-Klotho protein will be beneficial to the prevention and improvement of chronic diseases such as chronic cardiovascular disease, diabetes, chronic kidney disease and tumor. Therefore, it is speculated that promoting the expression of α-Klotho may be one of the mechanisms of exercise prevention and improvement of chronic diseases, but there is still a research gap on the mechanism of exercise promoting α-Klotho expression. In addition, the current research on the expression of plasma α-Klotho is aimed at healthy people, and the effect of exercise on the expression of α-Klotho in chronic diseases, such as chronic cardiovascular disease, diabetes, chronic kidney disease, is also needed to be studied more. The study of the mechanism of exercise prevention and improvement of chronic diseases provides a theoretical basis for the selection and formulation of related exercise programs, and may provide new ideas for the development of new drugs for chronic diseases. Therefore, studies on exercise to interfere with chronic diseases by promoting the expression of α-Klotho have good research prospects.

Introduction: This study endeavors to evaluate the distribution patterns and research frontiers within the international literature on the association between chronic kidney disease and cardiovascular diseases in the medical field, through bibliometric analysis and visualized information. Methods: The Web of Science Core Collection database was selected as the data source from 2010 to 2023, and articles related to the association between chronic kidney disease and cardiovascular diseases were retrieved. The article data were analyzed through CiteSpace for bibliometric mapping, involving the examination of keywords, references, country/region distributions, and institutional contributions to identify and understand the evolving research dynamics and frontiers in this interdisciplinary field. Results: A total of 2,936 publications on the association between chronic kidney disease and cardiovascular diseases were included. The country with the most publications was USA (n = 904), and the institution with the most publications was University of Pennsylvania (n = 116). The most frequent keywords were chronic kidney disease (n = 2,194), cardiovascular disease (n = 1,188), and mortality (n = 604). The top 20 keywords and top 10 references that burst during 2010 to 2023 were listed. Conclusion: The association between chronic kidney disease and cardiovascular diseases has sparked extensive research, particularly in high-prevalence areas. From 2010 to 2023, publications on the association between chronic kidney disease and cardiovascular diseases show a linear increase. Current research hotspots and frontiers are mainly in cardiovascular-kidney-metabolic syndrome; innovative therapies and drug impact; gut microbiome; Mendelian randomization analysis. Overall, our study offers a comprehensive scientometric analysis of the association between chronic kidney disease and cardiovascular diseases, providing valuable insights for both researchers and healthcare professionals in the field.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort

The effect of joint exposures: examining the presence of interaction

Perceived knowledge among patients cared for by nephrologists about chronic kidney disease and end-stage renal disease therapies

Screening for chronic kidney disease shows promise

Importance of Low-Grade Albuminuria

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) have major impacts upon the health of populations worldwide, especially in Western societies. The progression of CKD or CVD independently exerts synergistic deleterious effects on the other, for example, patients with CKD are more likely to die of CVD than to develop renal failure. This overlap between CKD and CVD, in part, relates to common etiologies such as diabetes mellitus and hypertension, but important dynamic and bidirectional interactions between the cardiovas‐ cular system and kidneys may also explain the occurrence of concurrent organ dysfunction [1]. Cardio-renal syndrome (or reno-cardiac syndrome, the prefix depending on the primary failing organ) is becoming increasingly recognised [2]. Conventional treatment targeted at either syndrome generally reduces the onset or progression of the other [3]. Even though our understanding of various factors and steps involved in the pathogenesis of CKD and CVD and their obvious links has improved, a complete picture of the mechanisms involved is still unclear. Oxidative stress has been identified as one unifying mechanism in the patho‐ genesis of CKD and CVD [4]. This current chapter gives a brief review of recent literature on the relationship between CKD, CVD and oxidative stress and indicates how, by applying knowledge of the molecular controls of oxidative stress, this information may help improve targeted therapy with antioxidants for these diseases.

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting. We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry. APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status (Pinteraction=0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models. APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus.

The incidence of chronic kidney disease is increasing worldwide, and the previously decreasing incidence of cardiovascular disease has now plateaued. Understanding the intersection of both heart and kidney disease is crucial. Chronic kidney disease and cardiovascular disease share common risk factors and specific pathogenic mechanisms and impact a significant segment of the population. Patients with chronic kidney disease are more likely to have cardiovascular disease than progress to end-stage kidney disease requiring renal replacement therapy. We discuss shared risk factors and mechanisms for cardiovascular and chronic kidney disease. The following also addresses contemporary cardiovascular treatment considerations in patients with chronic kidney disease with a focus on atherosclerotic cardiovascular disease and heart failure.

Cardiovascular Disease and CKD: Core Curriculum 2010