scholarly journals Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease

2022 ◽  
Vol 8 ◽  
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 < 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 < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 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 ◽  
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

2021 ◽  
Vol 11 (1) ◽  
Eric Yuk Fai Wan ◽  
Esther Yee Tak Yu ◽  
Weng Yee Chin ◽  
Christie Sze Ting Lau ◽  
Anna Hoi Ying Mok ◽  

AbstractThis study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45–84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008–2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m2) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15–1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30–1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74–2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10–1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26–1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46–2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability.

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1205
Yoshitaka Isaka

Multi-factors, such as anorexia, activation of renin-angiotensin system, inflammation, and metabolic acidosis, contribute to malnutrition in chronic kidney disease (CKD) patients. Most of these factors, contributing to the progression of malnutrition, worsen as CKD progresses. Protein restriction, used as a treatment for CKD, can reduce the risk of CKD progression, but may worsen the sarcopenia, a syndrome characterized by a progressive and systemic loss of muscle mass and strength. The concomitant rate of sarcopenia is higher in CKD patients than in the general population. Sarcopenia is also associated with mortality risk in CKD patients. Thus, it is important to determine whether protein restriction should be continued or loosened in CKD patients with sarcopenia. We may prioritize protein restriction in CKD patients with a high risk of end-stage kidney disease (ESKD), classified to stage G4 to G5, but may loosen protein restriction in ESKD-low risk CKD stage G3 patients with proteinuria <0.5 g/day, and rate of eGFR decline <3.0 mL/min/1.73 m2/year. However, the effect of increasing protein intake alone without exercise therapy may be limited in CKD patients with sarcopenia. The combination of exercise therapy and increased protein intake is effective in improving muscle mass and strength in CKD patients with sarcopenia. In the case of loosening protein restriction, it is safe to avoid protein intake of more than 1.5 g/kgBW/day. In CKD patients with high risk in ESKD, 0.8 g/kgBW/day may be a critical point of protein intake.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Jui-Ting Hsiung ◽  
Maria Marroquin ◽  
Kamyar Kalantar-Zadeh

Background: Studies suggests that in the general population, hyperlipidemia may confer higher risk of developing chronic kidney disease (CKD). But, there is conflicting data as to whether statins can protect renal function or slow renal degradation. We sought to examine the impact of statins on the association of low-density lipoprotein cholesterol (LDL) and risk of incident CKD. Methods: Our cohort included 1,439,756 US veterans without chronic kidney disease (CKD), but with LDL measured between 2004-2006, who were followed until 2014. Incident CKD was defined as over 3 estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.73m 2 at least 90 days apart. Patients with a statin prescription at the time of LDL measurement were identified. Cox models were used to estimate the associations between LDL with incident CKD. Model adjustments include demographics, comorbidities, smoking status, prescription of fibrate or niacin, body mass index, albumin, high-density lipoprotein cholesterol, and triglycerides. Results: The cohort included 5% females, 16% African Americans, 26% diabetics, and 30% statin-users, with a mean age of 60±13 years. The median [IQR] of LDL and eGFR were 109 [88,133] mg/dL and 83 [72,94] mL/min/1.73m 2 , respectively. A J-shaped association between LDL and incident CKD were observed in both those on statin and not on a statin after adjustment. Low LDL (<70 mg/dL) was associated with a higher risk of incident CKD compared to the reference (LDL 70-<100 mg/dL) regardless of statin use. High LDL ≥160 mg/dL was associated with the highest of risks of incident CKD (HR: 1.08, 95% CI: 1.04, 1.13, and HR: 1.10, 95% CI: 1.07, 1.12, for statin use and no statin use, respectively). Conclusion: Both high and low LDL were associated with higher incident CKD risk independent of statin use in this US veteran cohort. Further studies are needed to understand how to manage cardiovascular disease risk by lowering LDL while simultaneously reducing risk of CKD.

2011 ◽  
Vol 51 (4) ◽  
pp. 192 ◽  
Eka Laksmi Hidayati ◽  
Partini Pudjiati Trihono

Background Chronic kidney disease (CKD) in children is a potentially fatal disease if left untreated. Early detection and treatment are important to slow progression to end-stage renal disease requiring dialysis.Objective We aimed to find characteristics of CKD patients at admission and evaluate factors associated with end-stage CKD (stage 5).Methods Our cross-sectional study was based on medical records of CKD patients aged less than 18 years in Cipto Mangunkusumo Hospital, Jakarta, from January 2007 to December 2009. Diagnosis and stages of CKD were based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) criteria. Data on disease etiology, symptoms, nutritional status and laboratory tests were collected. Bivariate and multivariate analyses were performed to examine the association between end-stage CKD and its possible risk factors.Results Of the 142 cases eligible for analysis, 55% were boys. Subjects’ median age was 73.5 months (interquartile range of 23.5-122.5 months). Edema and recurrent fever were the two most frequent symptoms of CKD if diagnosed at stages 2-4, while breathlessness was the most frequent symptom of CKD if diagnosed at stage 5. The most common etiologies were glomerulonephritis (49.3%) and anomalies of the kidney and urinary tract (32.4%). Of our CKD subjects, 21.8% were in stage 5. Independent predictors of stage 5 CKD at presentation were hypertension (OR 3.88; 95% CI 1.17 to 12.87; P=0.026), urea level > 60 mg/dL (OR 39.11; 95%CI 4.86 to 314.74; P<0.001) and non-glomerulonephritis as the etiology (OR 6.51; 95%CI 2.12 to 19.92; P<0.001).Conclusion Glomerular disease was the most common cause of CKD in our study. Stage 5 CKD was present in 21.8% of subjects at admission and could be predicted by the presence of hypertension, high serum urea level, and non-glomerular disease as the etiology.

2020 ◽  
Vol 9 (11) ◽  
pp. 3702
Saraschandra Vallabhajosyula ◽  
Lina Ya’Qoub ◽  
Vinayak Kumar ◽  
Dhiran Verghese ◽  
Anna V. Subramaniam ◽  

Background: There are limited data on acute myocardial infarction with cardiogenic shock (AMI-CS) stratified by chronic kidney disease (CKD) stages. Objective: To assess clinical outcomes in AMI-CS stratified by CKD stages. Methods: A retrospective cohort of AMI-CS during 2005–2016 from the National Inpatient Sample was categorized as no CKD, CKD stage-III (CKD-III), CKD stage-IV (CKD-IV) and end-stage renal disease (ESRD). CKD-I/II were excluded. Outcomes included in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS). We also evaluated acute kidney injury (AKI) and acute hemodialysis in non-ESRD admissions. Results: Of 372,412 AMI-CS admissions, CKD-III, CKD-IV and ESRD comprised 20,380 (5.5%), 7367 (2.0%) and 18,109 (4.9%), respectively. Admissions with CKD were, on average, older, of the White race, bearing Medicare insurance, of a lower socioeconomic stratum, with higher comorbidities, and higher rates of acute organ failure. Compared to the cohort without CKD, CKD-III, CKD-IV and ESRD had lower use of coronary angiography (72.7%, 67.1%, 56.9%, 61.1%), PCI (53.7%, 43.8%, 38.4%, 37.6%) and MCS (47.9%, 38.3%, 33.3%, 34.2%), respectively (all p < 0.001). AKI and acute hemodialysis use increased with increase in CKD stage (no CKD–38.5%, 2.6%; CKD-III–79.1%, 6.5%; CKD-IV–84.3%, 12.3%; p < 0.001). ESRD (adjusted odds ratio [OR] 1.25 [95% confidence interval {CI} 1.21–1.31]; p < 0.001), but not CKD-III (OR 0.72 [95% CI 0.69–0.75); p < 0.001) or CKD-IV (OR 0.82 [95 CI 0.77–0.87] was predictive of in-hospital mortality. Conclusions: CKD/ESRD is associated with lower use of evidence-based therapies. ESRD was an independent predictor of higher in-hospital mortality in AMI-CS.

2019 ◽  
Vol 20 (10) ◽  
pp. 2470 ◽  
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.

2020 ◽  
Vol 41 (Supplement_1) ◽  
A B Md Radzi ◽  
S S Kasim

Abstract Background Arterial damage in chronic kidney disease (CKD) is characterized by aortic stiffness. This is seen in elderly patients with advanced CKD. The association between arterial stiffness and early CKD is not well established. Objective: We aimed to study arterial stiffness using pulse wave velocity (PWV) among patients with chronic kidney disease (CKD) stage 2 to 4 and normal renal function in younger-age population. Design and Method: Patients with confirmed CKD stage 2 to 4 were recruited from various clinics from Universiti Teknologi MARA Medical Center, Sungai Buloh, Malaysia from 1st August 2015 until 31st January 2018. Sociodemographic and anthropometric indices were recorded on recruitment. Each patient underwent carotid-femoral (aortic) PWV measurement to determine arterial stiffness. PWV is determined using a one-probe device (SphygmoSore XCEL). Results: 87 patients with CKD stage 2–4 and 87 control patients were recruited. The mean age was 47 ± 5.4 years. CKD patients had a higher mean PWV (7.8 m/s ± 1.7) than healthy controls (5.6 m/s ± 1.0) (p &lt; 0.001, 95% CI –2.59, –1.77). There was significant difference of mean PWV between control (5.6 m/s ± 1.0) and CKD stage 2 (7.6 m/s ± 1.5) (p &lt; 0.001, 95% CI –2.40, –1.49). Our results showed a stepwise increase in PWV from control subjects, CKD stage 2 through stage 4 (p &lt; 0.001). The mean difference of PWV between CKD stage 2 (7.6 m/s, ± 1.5) and stage 4 (9.0 m/s, ± 0.8) was 1.43 (p &lt; 0.001, 95% CI –2.50, -0.35). There was significant difference of mean PWV between diabetes mellitus (DM) (8.2 m/s ± 1.8) and non-DM (7.3 m/s ± 1.3) patients with CKD stage 2–4 (p = 0.022, 95% CI –1.50, –0.12). Mutiple linear regression analysis showed only age (β = 0.078, p = 0.014), mean arterial pressure (MAP) (β = 0.031, p = 0.007) and diuretics usage as the combination antihypertensive medication (β = 0.839, p = 0.018) were independently associated with PWV (r2 = 0.249, p &lt; 0.001). Conclusions: This study shows that arterial stiffness as assessed by PWV occurs early in CKD patient and increased arterial stiffness occurs in parallel with decline of glomerular filtration rate in patients with mild-to-moderate CKD of younger age population.

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