scholarly journals Markers of cholesterol metabolism and cardiovascular outcomes in patients with chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Emrich ◽  
K Rogacev ◽  
M Boehm ◽  
P.C Schulze ◽  
D Fliser ◽  
...  

Abstract Background In dialysis patients statins are less effective than in other high risk patients due to a shift from cholesterol synthesis towards cholesterol absorption. The CARE FOR HOMe study investigates whether a shift towards cholesterol absorption occurs in non-dialysis chronic kidney disease (CKD), and whether the ratio of campesterol-to-lathosterol predicts cardiovascular outcomes in non-dialysis CKD patients. Methods In this analysis 251 participants suffering from CKD (KDIGO 2–4) without lipid-lowering drugs were included and followed for major atherosclerotic events (MACE). Additionally, all-cause death and the composite endpoint MACE and all-cause death were explored. We performed univariate and multivariate Cox regression analysis, adjusting for age, gender, estimated glomerular filtration rate (eGFR), log-transformed albuminuria, prevalent cardiovascular disease, current smoking, diabetes mellitus, systolic blood pressure and body mass index. The primary hypothesis was that patients with a high campesterol-to-lathosterol ratio had a higher event rate. Results Neither lathosterol-to-cholesterol (r=0.022; p=0.730), nor campesterol-to-cholesterol (r=0.041; p=0.519) nor campesterol-to-lathosterol (r=−0.103; p=0.105) correlated with eGFR. During follow-up of 5.1±2.1 years, 47 participants suffered from MACE, 46 participants died and 61 reached the composite endpoint of MACE or all-cause death. In univariate Cox regression analysis, campesterol-to-lathosterol did not predict atherosclerotic cardiovascular events (HR 0.740; 0.368–1.487), all-cause death (HR 0.564; 0.277–1.145) or the composite endpoint (HR 0.652; 0.355–1.196). After full adjustment: campesterol-to-lathosterol was not associated with all three endpoints; MACE (HR 1.064; 0.507–2.231), all-cause death (HR 0.818; 0.420–1.594) and MACE and all-cause death (HR 0.956; 0.525–1.744). Conclusion Markers of cholesterol metabolism were not associated with eGFR in patients with impaired renal function (KDIGO 2–4). Campesterol-to-lathosterol did not predict future MACE or all-cause death in non-dialysis CKD. These findings do not support the concept that patients with impaired renal function (KDIGO 2–4) benefit in particular from ezetimibe treatment. Further research is required to address this hypothesis in dialysis patients. Funding Acknowledgement Type of funding source: None

2020 ◽  
pp. 1-9
Author(s):  
Noppawit Aiumtrakul ◽  
Puvanant Wiputhanuphongs ◽  
Ouppatham Supasyndh ◽  
Bancha Satirapoj

<b><i>Background:</i></b> Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population. <b><i>Objective:</i></b> The study aimed to examine the relationship between serum uric acid levels and impaired renal function. <b><i>Methods:</i></b> A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m<sup>2</sup>. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR &#x3c;60 mL/min/1.73 m<sup>2</sup> over 3 months. <b><i>Results:</i></b> A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid (<i>r</i> = −0.213, <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Insa Elena Emrich ◽  
Gunnar Henrik Heine ◽  
Schulze Christian ◽  
Kyrill S Rogacev ◽  
Danilo Fliser ◽  
...  

Abstract Background and Aims In dialysis patients, cholesterol-lowering therapy with statins is less effective than in other high-risk patients. This may partly be explained by a shift from cholesterol synthesis, which is inhibited by statin treatment, towards cholesterol absorption, which is inhibited by ezetimibe. In line, markers of cholesterol absorption – such as campesterol - better predict atherosclerotic cardiovascular events than markers of cholesterol synthesis – such as lathosterol - in dialysis patients. We now investigated in our CARE FOR HOMe study whether a similar shift towards cholesterol absorption occurs in non-dialysis chronic kidney disease (CKD), and whether the campesterol / lathosterol ratio predicts outcome in non-dialysis CKD patients. Method Since 2008, 599 participants suffering from chronic kidney disease have been included into the CARE FOR HOME study, an observational cohort study. 555 patients had baseline samples available for analyses of the lathosterol / cholesterol ratio as a marker for cholesterol synthesis, and the campesterol / cholesterol ratio as a marker for cholesterol absorption. We excluded those participants who were currently treated with statins or other lipid lowering drugs, leaving 251 patients for this analysis. Participants were followed annually for major atherosclerotic cardiovascular events (MACE), defined as non-fatal acute myocardial infarction, non-fatal ischemic stroke, cerebrovascular / peripheral arterial or coronary revascularization, major amputation above the ankle and cardiovascular death. Additionally, all-cause death and the composite endpoint MACE and all-cause death were explored. We performed univariate (Model 1) and multivariate Cox regression analysis, adjusting for age, gender (Model 2), estimated glomerular filtration rate (eGFR), log-transformed albuminuria (Model 3), prevalent cardiovascular disease, current smoking, diabetes mellitus, systolic blood pressure and body mass index (Model 4). The primary hypothesis was that patients with a high campesterol / lathosterol ratio had a higher event rate. Results Neither lathosterol / cholesterol ratio (r = 0.022, p = 0.730), nor campesterol / cholesterol ratio (r = 0.042; p = 0.519) nor the campesterol / lathosterol ratio (r = -0.103; p = 0.105) correlated significantly with eGFR. During follow-up of 5.1 ± 2.1 years, 47 participants suffered from MACE, 46 participants died and 61 participants reached the composite endpoint of MACE or all-cause death. In univariate Cox regression analysis, campesterol / lathosterol ratio did not significantly predict atherosclerotic cardiovascular events (HR 0.740; 0.368 – 1.487), all-cause death (HR 0.564; 0.277 – 1.145) or the composite endpoint (HR 0.652; 0.355 – 1.196). After full adjustment, results were not different: Campesterol / lathosterol ratio was not significantly associated with all three endpoints: MACE (HR 1.064; 0.507 – 2.231), all-cause death (HR 0.818; 0.420 – 1.594) and MACE and all-cause death (HR 0.956; 0.525 – 1.744). Conclusion We did not observe a shift from cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD. Campesterol / lathosterol ratio did not predict future MACE or all-cause death in non-dialysis CKD. These findings do not support the concept that CKD patients may preferentially benefit from ezetimibe rather than from statin treatment.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Boriani ◽  
M Proietti ◽  
C Laroche ◽  
E Fantecchi ◽  
M Popescu ◽  
...  

Abstract Background Several equations exist to estimate creatinine clearance according to serum creatinine values and baseline characteristics. The CKD-EPI equation is usually recommended in general population, while the Cockroft-Gault (CG) equation has been used in atrial fibrillation (AF) clinical trials. Purpose To perform a comparison between 6 different equations for evaluation of renal function in AF patients. Methods We calculated CKD-EPI, CG, body surface area adjusted CG (CG BSA), MDRD, BIS1 and FAS equations in AF patients enrolled in the EORP-AF Long-Term General Registry. Outcomes at 1-year follow-up were considered. Results Renal equations were calculated in 7725 patients. According to CKD-EPI mean (SD) creatinine clearance was 69.14 (21.06) mL/min/1.73 m2. Taking CKD-EPI as reference, the MDRD equation showed the highest agreement (weighted kappa [95% CI]: 0.843 [0.833–0.852]), while CK showed the lowest agreement (weighted kappa [95% CI]: 0.593 [0.580–0.606]. The remaining equations showed moderate agreement. Cox regression analysis showed that all equations were inversely associated with all major adverse outcomes [Figure]. The CKD-EPI equation showed modest predictive ability for the three outcomes (c-statistics: any TE/ACS/CV Death: 0.63379; CV Death: 0.68512; All-Cause Death: 0.67183), with all other equations reporting higher c-statistics (delta-c statistic ranging from +0.01497 for FAS equation for any TE/ACS/CV Death to +0.04547 for CG BSA for all-cause death) for all outcomes (all p<0.0001, for any equation for any outcome). Compared to CKD-EPI, all the other equations showed an improvement in prediction of outcomes, according to IDI and NRI, with the exception of FAS equation for any TE/ACS/CV Death. CG BSA equation showed the greatest improvement in prediction of outcomes compared to CKD-EPI (relative IDI: 21.9% for any TE/ACS/CV Death, 28.8% for CV Death, 34.4% for All-Cause Death). Cox Regression Analysis Conclusions Compared to CKD-EPI equation, all the other equations for creatine clearance has stronger associations with adverse outcomes, with the CG BSA reporting the higher yield for all the outcomes considered.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marios Theodoridis ◽  
Stylianos Panagoutsos ◽  
Ioannis Neofytou ◽  
Konstantia Kantartzi ◽  
Efthimia Mourvati ◽  
...  

Abstract Background and Aims Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD). The amount of protein lost will depend on dialysis time, protein size, its serum concentration and other factors including patients’ clinical status. Peritoneal protein loss may be a manifestation of endothelial dysfunction, as with another type of capillary protein leakage, microalbuminuria, a recognized endothelial dysfunction marker. The aim of this study was to retrospectively evaluate the influence of PPL on cardiovascular mortality of peritoneal dialysis patients Method This is a single center retrospective study of 84 PD patients (m=54, f=30) with mean age of 65.2±17 years, mean PD duration of 43.2±24.9 months conducted for the time period from 2006 to 2019 (13 years). The patients were divided into two groups according to the amount of protein excreted during the modified Peritoneal Equilibration Test (PET) procedure using PD solution of 3.86% DW, 2 Lt infusion volume for total time of 4 hours. The total amount of proteins excreted was calculate from PET by multiplying the concentration of proteins at the end of the test with the total volume of PD fluid at the same time. Group A excreted a total amount of proteins &lt; 1.55 gr (median value) at the end of PET test and Group B &gt; 1.55 gr. The cumulative all-cause and cardiovascular survival of the PD patients was calculated by Kaplan Meier while the possible effect of any parameter in survival rates was evaluated by using Cox Regression analysis Results There was not any statistically significant difference between the two groups according to PD duration, age, dialysis adequacy targets, Residual Renal Function(RRF), BMI, ultrafiltration volume during PET and their transport status. The cumulative all-cause survival using Kaplan-Meier analysis revealed no statistically significant deference between the two groups (Log Rank p=0.55) even though mortality risk was adjusted for several factors (Cox Regression). When cardiovascular survival, using Cox Regression analysis, was adjusted for age, sex, Diabetes, PD modality, dialysis Kt/V and RRF we found that Group A (with protein excretion &lt; 1.55 gr) had statistically significant better cardiovascular survival (p=0.029) compared to Group B. We confirm these results while trying to find among the total of our patients the possible risk factors for cardiovascular mortality. Using Cox Regression analysis, the amount of protein excreted during PET procedure and the type of PD solutions (high or low in GDPs) used were statistically significant (p=0.019 and p=0.04 respectively) independent risk factors for cardiovascular survival in our patients. Conclusion These results indicate that protein loss during peritoneal dialysis procedure has negative impact on cardiovascular mortality and survival of PD patients. Additionally, the use of PD solutions with low Glucose Degradation Products (GDPs) and AGEs may improve PD patient’s cardiovascular survival. Randomized interventional studies are encouraged to address the pathological concern of PPL in the future, namely its effects on cardiovascular conditions or its role as marker and effort to reduce PPL using ACE inhibitors or vit D should be considered only if it diminishes cardiovascular morbidity or mortality.


2020 ◽  
Vol 36 (1) ◽  
pp. 170-175
Author(s):  
Anita van Eck van der Sluijs ◽  
Alferso C Abrahams ◽  
Maarten B Rookmaaker ◽  
Marianne C Verhaar ◽  
Willem Jan W Bos ◽  
...  

Abstract Background Dialysis patients have an increased bleeding risk as compared with the general population. However, there is limited information whether bleeding risks are different for patients treated with haemodialysis (HD) or peritoneal dialysis (PD). From a clinical point of view, this information could influence therapy choice. Therefore the aim of this study was to investigate the association between dialysis modality and bleeding risk. Methods Incident dialysis patients from the Netherlands Cooperative Study on the Adequacy of Dialysis were prospectively followed for major bleeding events over 3 years. Hazard ratios with 95% confidence intervals (CIs) were calculated for HD compared with PD using a time-dependent Cox regression analysis, with updates on dialysis modality. Results In total, 1745 patients started dialysis, of whom 1211 (69.4%) received HD and 534 (30.6%) PD. The bleeding rate was 60.8/1000 person-years for HD patients and 34.6/1000 person-years for PD patients. The time-dependent Cox regression analysis showed that after adjustment for age, sex, primary kidney disease, prior bleeding, cardiovascular disease, antiplatelet drug use, vitamin K antagonist use, erythropoietin use, arterial hypertension, residual glomerular filtratin rate, haemoglobin and albumin levels, bleeding risk for HD patients compared with PD increased 1.5-fold (95% CI 1.0–2.2). Conclusions In this large prospective cohort of incident dialysis patients, HD patients had an increased bleeding risk compared with PD patients. In particular, HD patients with a history of prior bleeding had an increased bleeding risk.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nina Vodošek Hojs ◽  
Robert Ekart ◽  
Sebastjan Bevc ◽  
Nejc Piko ◽  
Radovan Hojs

Abstract Background and Aims Cardiovascular mortality is high in chronic kidney disease (CKD) patients. Recognizing patients with higher cardiovascular risk might help in their treatment. CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF). However, it is also useful in predicting outcome in different cardiovascular conditions, independent of the presence of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in cardiovascular mortality in CKD patients. Method Eighty-seven non-dialysis CKD patients from our outpatient clinic were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed for assigned time or until their death. Mean follow-up time was 1696.45±564.60 days. Results Descriptive statistics of our patients are presented in table 1. During follow-up 11 patients suffered from cardiovascular death. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular mortality (HR: 2.19, CI: 1.42-3.37, p=0.001). In multivariate Cox regression analysis in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, haemoglobin, high sensitivity CRP and intact PTH were included, CHA2DS2-VASc score was an independent predictor of cardiovascular mortality (HR: 2.04, CI: 1.20-3.45, p=0.008) (table 2). Conclusion CHA2DS2-VASc score is a simple and quick way to identify cardiovascular risk in CKD patients.


2019 ◽  
Vol 44 (1) ◽  
pp. 123-132 ◽  
Author(s):  
WenHan Bao ◽  
FangYu Wang ◽  
Wen Tang

Background/Aims: Possible predictive value of aortic-brachial arterial stiffness mismatch assessed by pulse wave velocity PWV ratio in peritoneal dialysis patients’ outcomes need to be further elucidated. The aim of this study is to investigate the predictor value of PWV ratio on peritoneal dialysis (PD) patients’ outcomes in China. Methods: In this longitudinal cohort study, patients who started PD during September 20, 2005, to February 05, 2008, were included. All the patients were followed until January 31, 2018. Aortic-brachial arterial stiffness mismatch was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity (PWV ratio). Results: A total of 181 incident PD patients were included. The median survival of patients in PWV ratio above median group (4.03 years, 95% CI 4.64-7.99 years) was shorter than that of PWV ratio below median group (10.43 years, 95% CI 9.74-11.12 years, p< 0.001). The cardiovascular mortality rate in PWV ratio above median group were significantly higher than that of PWV below median group (log rank test, p< 0.001). Univariate Cox regression analysis showed that both PWV ratio (HR 2.42, 95% CI 1.80-3.25, p< 0.001) and CF-PWV (HR 1.27, 95% CI 1.16-1.38, p< 0.001) were associated with high patients’ all-cause mortality. Multivariable Cox regression analysis showed that the PWV ratio was a strong and significantly predictor of cardiovascular mortality (HR 2.08 95% CI 1.16-3.71, p=0.014) after adjusting for coronary heart disease history (HR 2.39, 95% CI 1.20-4.76, p=0.013), diabetes mellitus history (HR 2.84, 95% CI 1.51-5.33, p=0.001). However, the CF-PWV was failed to be included as a significant predictor for both all-cause and CVD mortality in the multivariable Cox regression model. Conclusion: Aortic-brachial arterial stiffness mismatch as assessed by PWV ratio, a new arteries stiffness risk parameter, is a significant prognostic indicator of CVD mortality in PD patients. We demonstrated that the discriminative power of the PWV ratio for both all-cause and CVD mortality was better than that CF-PWV.


Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1375
Author(s):  
Borja Quiroga

Bisphenol A (BPA), also known as 2,2,-bis(4-hydroxyphenyl) propane, is a common component of plastics worldwide. However, it has been shown to act as an endocrine disruptor with some hormonal functions. Furthermore, high levels of BPA have been related to the development of cardiovascular events and the activation of carcinogenesis pathways. Patients with chronic kidney disease (CKD) have higher serum concentrations of BPA due to their impaired renal function. This situation is aggravated in CKD patients requiring dialysis, because the BPA content of dialysis devices (such as, for example, the filters) is added to the lack of excretion. In addition to the development of BPA-free dialysis filters, some techniques can contribute to the reduction of BPA levels in these patients. The aim of this review is to illustrate the impact of BPA on dialysis patients and suggest some strategies to reduce its inherent risks.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Robert Ekart ◽  
Gasper Keber ◽  
Nina Vodošek Hojs ◽  
Eva Jakopin ◽  
Nejc Piko ◽  
...  

Abstract Background and Aims Several factors may be responsible for the increased mortality in dialysis patients, but volume overload is considered among the main mechanisms of this association. Volume status is usually estimated using clinical criteria, i.e., patien's signs and symptoms, peridialytic blood pressure measurements, and intradialytic hemodynamic instability. Bioimpedance analysis (BIA) is another way to measure volume status in dialysis patients. BIA can measure overhydration (OH), extracellular water (ECW), intracellular water (ICW) and ECW/ICW ratio. The aim of our study was to analyze the role of BIA parameters before and after hemodialysis (HD) on all-cause mortality. Method Eighty-three patients (mean age 64.2 years; 51 men) on maintenance HD were included. BIA was performed and blood pressure was measured before and after the HD session. Patients were followed for assigned time, until transplantation or death. The mean follow-up time was 1181±564 days. Results Descriptive statistics of our patients are shown in Table 1. During the follow-up period, 6 (7.2%) patients were transplanted and 39 (47%) patients died. Univariate Cox regression analysis showed that only ICW before HD was a significant predictor of all-cause mortality (HR=1.089; 95%CI: 1.01-1.17, p=0.018). OH, ECW, ECW/ICW ratio before and after HD and ICW after HD were not associated with survival. In multivariate Cox regression analysis including ICW before dialysis, age, dialysis vintage, pulse pressure before HD, hemoglobin, CRP and serum albumin, ICW before dialysis was an independent predictor of all-cause mortality (HR=1.102; 95%CI: 1.01-1.20, p=0.029) (Table 2). Conclusion ICW before HD predicts all-cause mortality in HD patients.


2019 ◽  
Vol 9 (5) ◽  
pp. 297-307
Author(s):  
Qiong Bai ◽  
Chun-Yan Su ◽  
Ai-Hua Zhang ◽  
Tao Wang ◽  
Wen Tang

Background: In dialysis patients, loss of the normal gradient in arterial compliance, assessed by the pulse wave velocity (PWV) ratio, predicts all-cause mortality better than does carotid-femoral PWV (CF-PWV) alone. However, the prognostic significance of the PWV ratio for outcome in chronic kidney disease (CKD) patients remains unclear. Methods: In this longitudinal cohort study, CKD patients who visited our CKD management clinic between April 27, 2006, and March 27, 2008, were included and followed up. To assess the gradient in arterial compliance, the PWV ratio was calculated using CF-PWV divided by carotid-radial PWV. Results: A total of 209 patients in CKD stages 1–4 with a median follow-up of 3.74 years were included. Patients with higher PWV ratio were relatively older (p < 0.001) and had worse renal function (p < 0.001), more hypertension (p < 0.001), diabetes mellitus (p < 0.001), and cardiovascular or cerebrovascular disease (p < 0.001). The median time to patient outcome (death, renal replacement therapy, or double increase in serum creatinine from baseline) in the group with a PWV ratio above the median (89.8 months, 95% CI 84.2–95.5) was shorter than that in the group with a PWV ratio below the median (105.3 months, 95% CI 101.3–109.3, p = 0.001). Univariate Cox regression analysis showed that both PWV ratio and CF-PWV were significantly associated with patient outcome. In multivariate Cox regression analysis, both PWV ratio and CF-PWV were associated with patient outcome. However, the HR for CF-PWV (2.177, 95% CI 1.064–4.453, p = 0.033) was slightly higher than that for PWV ratio (2.091, 95% CI 1.049–4.167, p = 0.036). There was a significant interaction effect between PWV ratio and CKD stage. It was shown that patients with advanced CKD stages and higher PWV ratios had a significantly higher risk of adverse CKD outcome (p = 0.006). Conclusions: The PWV ratio, as a measure of loss of the normal gradient in arterial compliance, was associated with CKD patient outcome. Patients with advanced CKD and a higher PWV ratio had a significantly higher risk of adverse CKD outcome.


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