Independent, Non-traditional Risk Factors for Cardiovascular Events and Atherothrombosis in Chronic Kidney Disease and in Hemodialysis-dependent Patients

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.

Download Full-text

Traditional and non-traditional risk factors for incident peripheral arterial disease among patients with chronic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv418 ◽

2015 ◽

Vol 31 (7) ◽

pp. 1145-1151 ◽

Cited By ~ 23

Author(s):

Jing Chen ◽

Emile R. Mohler ◽

Dawei Xie ◽

Michael Shlipak ◽

Raymond R. Townsend ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Peripheral Arterial Disease ◽

Arterial Disease ◽

Traditional Risk Factors ◽

Peripheral Arterial

Download Full-text

SAT-LB96 Chronic Kidney Disease Incidence and Cardiorespiratory Fitness Association in Patients With Diabetes And/Or Hypertension

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2104 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Joseph Powell ◽

Eric S Nylen ◽

Jonathan Myers ◽

Pamela Karasik ◽

Hans Moore ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Cardiorespiratory Fitness ◽

Cox Regression ◽

Disease Incidence ◽

Metabolic Equivalents ◽

Patients With Diabetes ◽

Exercise Treadmill ◽

Traditional Risk Factors

Abstract Introduction: Type 2 diabetes mellitus (T2DM) and hypertension (HTN) are considered strong risk factors for developing chronic kidney disease (CKD). Increased cardiorespiratory fitness (CRF) is associated with lower CKD risk. However, the CRF-CKD association in patients with T2DM and/or HTN has not been assessed.Methods: We identified 9,751 patients (age 58.6 + 10.1 years) with T2DM (N=1,444) or HTN (n=5,031) or both (n=3,276) prior to a maximal standardized exercise treadmill test (ETT) and no evidence of ischemia as indicated by the ETT. We established four CRF categories based on age-adjusted peak metabolic equivalents (METs) achieved: Least-Fit (4.6±1.2 METs; n=2,231); Low-Fit Fit (6.4±1.1 METs; n=2,693); Moderate-Fit (8.0±1.0 METs; n=2,432); and High-Fit (10.8±2.1 METs; n=2,395). We performed multivariable Cox Regression analyses to access the risk of CKD according to fitness. The models were adjusted for age, body mass index (BMI), traditional risk factors and medications. Results: During the median follow-up of 12.4 years, 1,118 patients developed CKD, accounting for 9.1 events/ 1,000 person-years of observation. The association between CRF and CKD was inverse and graded. The risk of CKD was 21% lower (Hazard Ratio [HR] 0.79; 95% confidence interval [CI] 0.77-0.81). When CRF categories were considered, the CKD risk was 44% lower for Moderate-Fit patients (HR 0.56; 95% CI 0.48-0.67) and 80% lower for High-Fit (HR 0.20; 95% CI 0.15-0.25). Similar findings were noted in patients with both T2DM and HTN. Conclusions: We noted an inverse and dose-response association between CRF and CKD incidence. The risk was attenuated significantly beyond a mean peak MET level of 8.0±1.0, suggesting that moderate increases in exercise capacity confers favorable health benefits in patients at high risk of developing CKD.

Download Full-text

Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A Primer

Journal of the American Society of Nephrology ◽

10.1681/asn.2020121760 ◽

2021 ◽

pp. ASN.2020121760

Author(s):

Adrienne Tin ◽

Anna Köttgen

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Mendelian Randomization ◽

Mr Studies ◽

Causal Relationships ◽

Omics Technologies ◽

Basic Concepts ◽

Traditional Risk Factors ◽

Randomization Analysis

Many Mendelian randomization (MR) studies have recently been published, with inferences on the causal relationships between risk factors and diseases that have potential implications for clinical research. In nephrology, MR methods have been applied to investigate potential causal relationships of traditional risk factors, lifestyle factors, and biomarkers from omics technologies with kidney function or chronic kidney disease. This primer summarizes the basic concepts of MR studies, highlighting methods employed in recent applications, and emphasizes key elements in conducting and reporting of MR studies that are important for interpreting the results.

Download Full-text

Cardiovascular Risk Factors in Pre-dialysis Chronic Kidney Disease patients of Nepal

Journal of Advances in Internal Medicine ◽

10.3126/jaim.v9i2.32813 ◽

2020 ◽

Vol 9 (2) ◽

pp. 47-53

Author(s):

Kashyap Dahal ◽

A. Baral ◽

K.K. Sah ◽

J.R. Shrestha ◽

A. Niraula ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Logistic Regression ◽

Regression Analysis ◽

Kidney Disease ◽

Multiple Logistic Regression Analysis ◽

Multiple Logistic Regression ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Traditional Risk Factors

Background and Aims: Cardiovascular disease (CVD) is the commonest cause of morbidity and mortality in patients with chronic kidney disease (CKD) due to increased prevalence of traditional and nontraditional CVD risk factors. Our study aimed to evaluate these risk factors in pre-dialysis Nepalese CKD patients. Methods: This was a cross-sectional study conducted in Department of Nephrology, Bir hospital. Total 100 consecutive pre-dialysis CKD patients were enrolled. Ten traditional and six nontraditional CVD risk factors were analyzed and compared between CKD stages. Descriptive statistics was used to illustrate the socio-demographic and clinical characteristics, chi square test for categorical variables and multiple logistic regression analysis was done to determine the risk factors of CVD in CKD patients. p-value<0.05 was considered to be statistically significant. Results: Mean patient age was 52.03}13.64 years with majority (60%) of the patients being male. Comparison of traditional risk factors in different stages depicted similar trend except for old age in Stage 3 CKD (p=0.002). Anemia (p<0.001), hyperphosphatemia (p=0.01), hyperparathyroidism (p<0.01) and cumulative nontraditional risk factors were significantly higher (p=0.01) in stage 5 CKD. The predicted CVD events by Framingham risk score showed high risk in 37% with no significant difference among the stages. Multiple logistic regression analysis showed increased body mass index, low serum albumin and increased serum phosphate as the three significant predictors for left ventricular hypertrophy. Conclusion: Our study shows that the CVD risk factors were prevailing along the various stages of CKD. The occurrence of non-traditional risk factors increased with increasing stage of CKD.

Download Full-text

A Pilot Randomized Crossover Trial Assessing the Safety and Short-Term Effects of Walnut Consumption by Patients with Chronic Kidney Disease

10.20944/preprints201911.0030.v1 ◽

2019 ◽

Author(s):

Pilar Sanchis ◽

Marilisa Molina ◽

Francisco Berga ◽

Elena Muñoz ◽

Regina Fortuny ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Dietary Supplement ◽

Cardiovascular Events ◽

Inositol Phosphates ◽

Control Diet ◽

Fibroblast Growth Factor 23 ◽

Short Term ◽

Daily Consumption

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, cross-over, pilot clinical trial examined 13 patients with chronic kidney disease (CKD). Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and serum albumin, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23. Consequently, this dietary supplement may prevent cardiovascular events in patients with CKD.

Download Full-text

Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease

Diagnostics ◽

10.3390/diagnostics11081518 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1518

Author(s):

Mădălina Ioana Moisi ◽

Simona Gabriela Bungau ◽

Cosmin Mihai Vesa ◽

Camelia Cristina Diaconu ◽

Tapan Behl ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Clinical Approach ◽

Coronary Syndrome ◽

Inflammatory Status ◽

Ischemic Coronary Artery Disease ◽

Improper Use ◽

Traditional Risk Factors ◽

Artery Disease

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation – fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient’s survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.

Download Full-text

P5526Vascular endothelial growth factor-D and mortality in suspected or known coronary heart disease patients with chronic kidney disease: a subanalysis of the ANOX study

European Heart Journal ◽

10.1093/eurheartj/ehz746.0474 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Wada ◽

M Suzuki ◽

M Matsuda ◽

Y Ajiro ◽

T Shinozaki ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Coronary Heart Disease ◽

Heart Disease ◽

Growth Factor ◽

Kidney Disease ◽

Coronary Angiography ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Endothelial Growth Factor

Abstract Background Chronic kidney disease (CKD) is an independent risk factor for the development and progression of coronary heart disease (CHD). Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 (Flt-4) and VEGFR-2 (KDR/Flk-1). VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to CHD. VEGF-D signaling has been used as a therapeutic target of human diseases such as lymphangioleiomyomatosis and refractory angina. Furthermore, in clinical settings, the VEGF-D level is already established as a diagnostic biomarker for lymphangioleiomyomatosis. However, the prognostic value of VEGF-D in suspected or known CHD patients with CKD is unknown. Methods Serum VEGF-D levels were measured in 999 suspected or known CHD patients with CKD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 154 patients died from any cause, 61 died from cardiovascular disease, and 96 developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.41; 95% confidence interval [CI], 1.27–1.56), cardiovascular death (HR, 1.48; 95% CI, 1.28–1.71), and MACE (HR, 1.34; 95% CI, 1.18–1.53). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.272; 95% CI, 0.100–0.445; P=0.002; integrated discrimination improvement [IDI], 0.015; 95% CI, 0.003–0.027; P=0.013), but not that of cardiovascular death (NRI, 0.230; 95% CI, −0.029 to 0.488; P=0.082; IDI, 0.012; 95% CI, −0.007 to 0.031; P=0.207) or MACE (NRI, 0.102; 95% CI, −0.106 to 0.310; P=0.337; IDI, 0.005; 95% CI, −0.005 to 0.015; P=0.337). Conclusions In suspected or known CHD patients with CKD undergoing elective coronary angiography, elevated VEGF-D levels may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers. Acknowledgement/Funding The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization

Download Full-text

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm8071034 ◽

2019 ◽

Vol 8 (7) ◽

pp. 1034 ◽

Cited By ~ 7

Author(s):

Chrysan J. Mohammed ◽

Yanmei Xie ◽

Pamela S. Brewster ◽

Subhanwita Ghosh ◽

Prabhatchandra Dube ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Clinical Outcomes ◽

Prognostic Value ◽

Oxidant Stress ◽

Adverse Outcomes ◽

Protein Levels ◽

Traditional Risk Factors ◽

Apparently Healthy

The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD.

Download Full-text