scholarly journals Plasma Levels of Preβ1-HDL Are Significantly Elevated in Non-Dialyzed Patients with Advanced Stages of Chronic Kidney Disease

2019 ◽  
Vol 20 (5) ◽  
pp. 1202 ◽  
Author(s):  
Agnieszka Kuchta ◽  
Agnieszka Ćwiklińska ◽  
Monika Czaplińska ◽  
Ewa Wieczorek ◽  
Barbara Kortas-Stempak ◽  
...  

In chronic kidney disease (CKD), the level of high-density lipoprotein (HDL) decreases markedly, but there is no strong inverse relationship between HDL-cholesterol (HDL-C) and cardiovascular diseases. This indicates that not only the HDL-C level, but also the other quantitative changes in the HDL particles can influence the protective functionality of these particles, and can play a key role in the increase of cardiovascular risk in CKD patients. The aim of the present study was the evaluation of the parameters that may give additional information about the HDL particles in the course of progressing CKD. For this purpose, we analyzed the concentrations of HDL containing apolipoprotein A-I without apolipoprotein A-II (LpA-I), preβ1-HDL, and myeloperoxidase (MPO), and the activity of paraoxonase-1 (PON-1) in 68 patients at various stages of CKD. The concentration of HDL cholesterol, MPO, PON-1, and lecithin-cholesterol acyltransferase (LCAT) activity were similar in all of the analyzed stages of CKD. We did not notice significant changes in the LpA-I concentrations in the following stages of CKD (3a CKD stage: 57 ± 19; 3b CKD stage: 54 ± 15; 4 CKD stage: 52 ± 14; p = 0.49). We found, however, that the preβ1-HDL concentration and preβ1-HDL/LpA-I ratio increased along with the progress of CKD, and were inversely correlated with the estimated glomerular filtration rate (eGFR), even after adjusting for age, gender, triacylglycerols (TAG), HDL cholesterol, and statin therapy (β = −0.41, p < 0.001; β = −0.33, p = 0.001, respectively). Our results support the earlier hypothesis that kidney disease leads to the modification of HDL particles, and show that the preβ1-HDL concentration is significantly elevated in non-dialyzed patients with advanced stages of CKD.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.


Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel Guldager Kring Rasmussen ◽  
Lene Boesby ◽  
Signe Holm Nielsen ◽  
Martin Tepel ◽  
Sophie Birot ◽  
...  

Abstract Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2–5 patients by measuring peptides reflecting formation and degradation of collagen type (COL) I, III, IV, and VI. Based on the collagen turnover profile, we identified four clusters of patients. Cluster 1 contained one patient with prostate cancer, who had a distinct collagen turnover. The other clusters generally had severe (Cluster 2), moderate (Cluster 4), or mild CKD (Cluster 3). Cluster 4 patients were characterized by higher levels of COL III, COL IV, and COL VI (all p < 0.001) degradation fragments in plasma, while patients in Clusters 2 and 4 had higher levels of COL VI formation (p < 0.05). COL IV fragments in plasma were lower in Cluster 2 (p < 0.01). Urinary COL III fragments decreased from Cluster 3 to 4, and from Cluster 4 to 2 (both p < 0.001). We show that patients with similar kidney function have a different collagen remodeling profile, suggesting that different phenotypes exist with different disease activity and potentially disease progression. Biomarkers of collagen remodeling could provide additional information to traditional markers of renal function.


2019 ◽  
Vol 20 (10) ◽  
pp. 2470 ◽  
Author(s):  
Aleksandra Czumaj ◽  
Tomasz Śledziński ◽  
Juan-Jesus Carrero ◽  
Piotr Stepnowski ◽  
Malgorzata Sikorska-Wisniewska ◽  
...  

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Schmucker ◽  
A Fach ◽  
R Osteresch ◽  
T Retzlaff ◽  
S Michel ◽  
...  

Abstract Background Current guidelines on the management of patients with ST-elevation myocardial infarction (STEMI) recommend the preferred use of the modern P2Y12-inhibitors ticagrelor or prasugrel regardless of the presence of chronic kidney disease (CKD), although patients with advanced stages of CKD were excluded from randomized trials. Aim of the present study was therefore to evaluate the potential benefit of modern P2Y12-inhibitors in patients with and without advanced renal disease at admission. Methods All patients admitted with STEMI between 2006–2017 from a large german heart center treated with primary percutaneous coronary intervention (PCI) entered analysis. Initial CKD was estimated with the initial glomerular filtration rate (GFR), calculated with the CKD-EPI-equation, assigning them to the groups G1-G5. Results Of 7227 patients with STEMI and primary PCI 2669 (37%) showed no relevant reduction in GFR at admission (≥90 ml/min/1.73 m2, G1), 2976 pts. (41%), a slight reduction (GFR 60–89 ml/min/1.73 m2, G2), 880 pts. (12%) a moderate reduction (GFR 45–59 ml/min/1.73 m2, G3a) and 702 pts. (10%) a moderate to severe reduction (GFR<45 ml/min 1.73 m2, G3b-G5). Pts. with more advanced stages of CKD were on average older (G1: 55±11 years, G2: 66±12 years, G3a: 72±12 years, G3b-G5: 75±11 years, p<0.01) and more likely to be female (G1: 19%, G2: 26%, G3a: 40%, G3b-G5: 48%, p<0.01). Prasugrel/ticagrelor were less often given instead of clopidogrel in patients with advanced CKD (G1: 70%, G2: 45%, G3a: 31%, G3b-G5: 32%, p<0.01). The use of ticagrelor/prasugrel was associated with a reduction in 1-year-MACCE (major adverse cardio- and cerebrovascular events)-rates in patients with no/low-grade-CKD (G1-G2), while no significant reduction in MACCE could be observed for patients with moderate to severe CKD (table). Furthermore, CKD was associated with an elevation in severe bleeding events within 1 year (G1: 1%, G2: 3%, G3a: 5%, G3b-G5: 6%, p<0.01). Impact of CKD-stage on outcome CKD-stage G1 CKD-stage G2 CKD-stage G3a CKD-stage G3b-G5 1-year-MACCE-rate (%) Ticagrelor/prasugrel 4.5 11.0 27.4 47.3 Clopidogrel 9.9 15.6 26.6 50.4 Significance <0.01 <0.01 0.6 0.7 Conclusions These data from a large STEMI-registry demonstrate, that modern P2Y12-inhibitors were less often used in patients with CKD and their benefit regarding MACCE disappeared in advanced stages of CKD while bleeding rates increased. These results underline the special role of patients with advanced stage-CKD in STEMI and the necessity of specialized randomized trials for these patients.


2019 ◽  
Author(s):  
Li Wang ◽  
Fangfang Xiang ◽  
Jun Ji ◽  
Jianzhou Zou ◽  
Yunqin Chen ◽  
...  

Abstract Background: High indoxyl sulfate (IS) levels and low high-density lipoprotein cholesterol (HDL-c) levels are both risk factors of cardiovascular diseases (CVD) in chronic kidney disease (CKD) patients, the connection between which has not been clearly clarified. This study aimed to explore the relationship between IS and HDL-c levels in early stages of CKD population. Methods: Patients of CKD stage 1-3 were enrolled in this cross-sectional study. Correlations between HDL-c and IS were investigated among various clinicopathological variables.Results: A total of 205 CKD patients (96 men) with a mean age of 43.3 years old were included in this research. There were 96 patients (46 men) in CKD stage1 and 109 (50 men) in CKD stage 2 or stage 3. IS levels were significantly higher in CKD 2+3 group (1.50±1.74μg/ml vs 0.94±0.66μg/ml, p=0.007), while HCL-c levels were lower (1.19±0.39mmol/L vs 1.33±0.45 mmol/L, p=0.017) compared to CKD 1 group. Among all the patients, a negative correlation was observed between IS and HDL-c levels (r=-0.244, p=0.001). IS level was an independent risk factor for low HDL-c (<1.04mmol/L) incidence even after controlling for potential confounders (OR=1.63, 95% CI: 1.11-2.39, p=0.013). IS and HDL-c were both risk factors for predicting CKD stage 3. Conclusions: Metabolic disorder of HDL-c occurs in early CKD stages, probably attributed by increased IS level. Early management of dyslipidemia and uremic toxin retention is important for delaying disease progression and preventing cardiovascular events. Keywords: Indoxyl sulfate, High-density lipoprotein cholesterol, Chronic kidney disease, Cardiovascular disease, Lipids


Biomedicine ◽  
2021 ◽  
Vol 40 (4) ◽  
pp. 442-446
Author(s):  
Chaganti Sridevi ◽  
UVPU Sowjanya ◽  
V. S. Kalai Selvi ◽  
DMM Rajakumari ◽  
Kasi Babu

Introduction and Aim: CKD (Chronic Kidney Disease) is a problem in health care spread all over the world with adverse consequences. CKD is associated with premature atherosclerosis and increased morbidity and mortality due to cardiovascular complications. Hypertriglyceridemia is a commonly seen lipid abnormality in CKD patients. PON-1 (Paraoxanase-1) is a glycoprotein synthesized in the liver and is released into the blood, where it links with HDL. This study was undertaken to find out the relation between PON-1 and HDL-C and its effect on atherosclerosis.  Materials and Methods: A total number of 123 subjects participated in the study. Serum was used for estimating the parameters such as serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) by calculation, creatinine, urea in a fully automated analyzer BS300. Serum paraoxonase-1(PON) was estimated by spectrophotometric method. Results: The metabolic derangement was very evident in the CKD group with significantly higher creatinine, urea, and dyslipidemia, and abnormal paraoxonase activity being observed in the cases compared to controls.  Conclusion: This study suggests the need for assessing PON-1 activity, a measure of the antioxidant capacity of HDL-C which improves the predictive accuracy of atherosclerosis in CKD.


2021 ◽  
Author(s):  
Saba Alvand ◽  
Farhad Abolnezhadian ◽  
Sudabeh Alatab ◽  
Zahra Mohammadi ◽  
Fatemeh Hayati ◽  
...  

Abstract Background: Chronic kidney disease (CKD) is a growing global health problem with faster progression in developing countries such as Iran. Here we aimed to evaluate the prevalence and determinants of CKD stage III+.Methods: This research is part of the Khuzestan Comprehensive Health Study (KCHS), a large observational population-based cross-sectional study in which 30041 participants aged 20 to 65 were enrolled. CKD was determined with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2, based on two equations of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The multivariate logistic regression was used to evaluate the CKD stage III+ determinants.Results: Prevalence of CKD stage III+ is estimated to be 7.1 %, 5.5%, and 5.4% based on MDRD, CKD-EPI, and combination of both equations, respectively. More than 89% of CKD subjects aged higher than 40 years. In regression analysis, age more than 40 years had the strongest association with CKD stage III+ probability (OR: 8.23, 95% CI: 6.91-9.18). Higher wealth score, hypertension, High-Density Lipoprotein levels less than 40 mg/dl, and higher waist to hip ratio were all associated with CKD stage III+ while Arab ethnicity showed a protective effect (OR: 0.69, 95% CI: 0.57-0.78). Conclusion: Our findings provide detailed information on the CKD stage III+ and its determinants in the southwest region of Iran. Due to strong association between age and CKD stage III+, within a few decades we might expect a huge rise in the CKD prevalence.


2020 ◽  
Vol 9 (7) ◽  
pp. 2289 ◽  
Author(s):  
Andrea Baragetti ◽  
Alice Ossoli ◽  
Arianna Strazzella ◽  
Sara Simonelli ◽  
Ivano Baragetti ◽  
...  

Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 554
Author(s):  
Susana Coimbra ◽  
Flávio Reis ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Cristina Catarino ◽  
...  

Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population of particles with different atherogenic or atheroprotective properties. HDL-cholesterol concentrations per se may not entirely reflect a beneficial or a risk profile for CVD. Large HDL in CKD patients may have a unique proteome and lipid composition, impairing their cholesterol efflux capacity. This lack of HDL functionality may contribute to the paradoxical coexistence of increased large HDL and enhanced risk for CVD events. Moreover, CKD is associated with inflammation, oxidative stress, diabetes, and/or hypertension that are able to interfere with the anti-inflammatory, antioxidative, and antithrombotic properties of HDL subpopulations. How these changes interfere with HDL functions in CKD is still poorly understood. Further studies are warranted to fully clarify if different HDL subpopulations present different functionalities and/or atheroprotective effects. To achieve this goal, the standardization of techniques would be valuable.


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