scholarly journals Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism

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 ◽  
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


Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 98
Author(s):  
Justyna Korczyńska ◽  
Aleksandra Czumaj ◽  
Michał Chmielewski ◽  
Maciej Śledziński ◽  
Adriana Mika ◽  
...  

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC–MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.


1994 ◽  
Vol 303 (1) ◽  
pp. 213-216 ◽  
Author(s):  
Y Zhu ◽  
A G Goodridge ◽  
S R Stapleton

Insulin regulates the expression of genes involved in a variety of metabolic processes. In chick-embryo hepatocytes in culture, insulin amplifies the tri-iodothyronine (T3)-induced enzyme activity, and the level and rate of transcription of mRNA for both fatty acid synthase (FAS) and malic enzyme (ME). Insulin alone, however, has little or no effect on the expression of these genes. In chick-embryo hepatocytes, the mechanism by which insulin regulates the expression of these or other genes is not known. Several recent studies have compared the effects of zinc, vanadate and selenate on insulin-sensitive processes in an attempt to probe the mechanism of insulin action. Because zinc, vanadate and selenate mimic the effects of insulin on several processes, they have been termed insulin-mimetics. We have studied the effect of zinc, vanadate and selenate on the T3-induced expression of both FAS and ME. Like insulin, these agents had little or no effect on the basal activities for FAS and ME in chick-embryo hepatocytes in culture for 48 h. Unlike insulin, however, zinc, vanadate and selenate inhibited the T3-induced activities and mRNA levels of both FAS and ME. Maximal inhibition was achieved at concentrations of 50 microM zinc or vanadate, or 20 microM selenate. Zinc and vanadate also inhibited the T3-induced transcription of the FAS and ME genes. Although the mechanism of this inhibition is unknown, our results indicate that it is not mediated through inhibition of binding of T3 to its nuclear receptor nor through a general toxic effect. Thus zinc, vanadate and selenate are not insulin-mimetics under all conditions, and their effects on other insulin-sensitive processes may be fortuitous and unrelated to actions or components of the insulin signalling pathway.


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.


2021 ◽  
Vol 22 (1) ◽  
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 30,041 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.


2022 ◽  
Vol 8 ◽  
Author(s):  
Momoko Matsuyama ◽  
Keiji Hirai ◽  
Hiroaki Nonaka ◽  
Moeka Ueda ◽  
Junki Morino ◽  
...  

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p &lt; 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p &lt; 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p &lt; 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.


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.


2016 ◽  
Vol 35 (4) ◽  
pp. 436-442 ◽  
Author(s):  
Miron Sopić ◽  
Jelena Joksić ◽  
Vesna Spasojević-Kalimanovska ◽  
Nataša Bogavac-Stanojević ◽  
Sanja Simić-Ogrizović ◽  
...  

SummaryBackground:Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects.Methods:This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR.Results:Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=−0.472, P=0.006; HD: r=−0.375, P=0.038), triglycerides (CG: r=−0.490, P=0.004; HD: r=−0.488, P=0.005), insulin (CG: r=−0.386, P=0.038; HD: r=−0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=−0.672, P<0.001; HD: r=−0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups.Conclusions:Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of »adiponectin resistance«.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Basma Sultan ◽  
Hamdy Omar ◽  
Housseini Ahmed ◽  
Mahmoud Elprince ◽  
Osama Anter adly ◽  
...  

Abstract Background and Aims Vascular calcification (VC) plays a major role in cardiovascular disease (CVD), which is one of the main causes of mortality in patients with chronic kidney disease (CKD). The study aims at early detection of breast arterial calcification (BAC) in different stages of CKD (stage 2, 3& 4) patients as an indicator of systemic VC. Method A case control study was conducted targeting CKD women, aged 18- 60 years old. The sample was divided into 3 groups; A,B,C (representing stage 2, 3 & 4 of CKD) from women who attended nephrology and Internal medicine clinics and admitted in inpatient ward in Suez Canal University Hospital. A 4th group (D) was formed as a control group and included women with normal kidney functions (each group (A, B, C, D) include 22 women). The selected participants were subjected to history taking, mammogram to detect BAC and biochemical assessment of lipid profile, Serum creatinine (Cr), Mg, P, Ca, PTH and FGF23. Results Our study detected presence of BAC in about 81.8% of hypertensive stage 4 CKD patients compared with 50% in stage 3 CKD, also in the majority of stage 4 CKD patients who had abnormal lipid profile parameters and electrolyte disturbance. Most of the variables had statistical significance regarding the presence of BAC. Conclusion Although it is difficult to determine the definite stage at which the risk of VC begins but in our study, it began late in stage 2 CKD, gradually increased prevalence through stage 3 and became significantly higher in stage 4. These results suggest that preventive strategies may need to begin as early as stage 2 CKD.


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