scholarly journals SUN-592 Adipocyte Specific Endothelin a Receptor Knockout Increases Adiposity in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Osvaldo Rivera-Gonzalez ◽  
Joshua S Speed
Keyword(s):  
Chronic Kidney Disease ◽  
Body Weight ◽  
Kidney Disease ◽  
Plasma Lipids ◽  
Human Adipocyte ◽  
Endothelin 1 ◽  
Endothelin A Receptor ◽  
Eta Receptor ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Abstract Obesity is associated with increased levels of Endothelin-1 (ET-1). Blockade of ET-1 type A receptors (ETA) improves lipid profile in patients with chronic kidney disease; however the mechanism is unknown.[1] In adipocytes ETA activation increases lipolysis, a potential mechanism for elevated lipids in obese individuals.[2] Therefore, the goal of this study was to determine if adipocyte specific knockout (KO) of the ETA receptor in mice alters genes associated with lipid metabolism in adipose and improves plasma lipids. 24-week old adipocyte ETA knockout mice had significantly elevated body weight compared to floxed controls (32.6±1.0 vs. 29.5±0.7 g respectively). Echo MRI revealed that the increased body weight was due to greater adiposity (10.1±0.9 vs. 14.7±1.8 % body weight; floxed vs. KO), while no statistical difference was observed in lean weight (88.9±2.4 vs. 86.8±2.6 % body weight; floxed vs. KO). Surprisingly, there were no statistical differences in plasma total cholesterol or triglycerides. RNA sequencing indicated downregulation of 597 genes and upregulation of 444 genes in visceral adipose and downregulation of 368 and upregulation of 847 genes in subcutaneous adipose. KEGG pathway analysis revealed that most genes altered in visceral adipose were related to metabolic pathways. These data implicate a role for adipose tissue ETA receptors in regulating adiposity and promoting pathophysiology related to obesity. 1. Farrah, T.E., et al., Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease. Hypertension, 2019. 74(2): p. 323-330. 2. Eriksson, A.K., et al., Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor. Int J Obes (Lond), 2009. 33(1): p. 67-74.

scholarly journals Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

2020 ◽  
Author(s):  
Dominique M. Bovée ◽  
Lodi C. W. Roksnoer ◽  
Cornelis van Kooten ◽  
Joris I. Rotmans ◽  
Liffert Vogt ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sodium Chloride ◽  
Kidney Disease ◽  
Sodium Bicarbonate ◽  
Renin Angiotensin System ◽  
Ammonium Excretion ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelin 1 ◽  
Plasma Bicarbonate

Abstract Background Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis. Methods Patients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed. Results Forty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05). Conclusions Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity. Graphic abstract

scholarly journals Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3381
Author(s):  
Sang Heon Suh ◽  
Tae Ryom Oh ◽  
Hong Sang Choi ◽  
Chang Seong Kim ◽  
Eun Hui Bae ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Body Weight ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Body Weight Gain ◽  
Absolute Difference ◽  
Composite Outcome ◽  
Increased Risk ◽  
All Cause Mortality

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.

scholarly journals EFFECT OF SUBCUTANEOUS RECOMBINANT HUMAN ERYTHROPOIETIN ON BLOOD PRESSURE IN PRE-DIALYSIS CHRONIC KIDNEY DISEASE (CKD) PATIENTS

2021 ◽  
Vol 71 (1) ◽  
pp. 261-65
Author(s):  
Muhammad Sajid Hussain ◽  
Qasim Raza ◽  
Muhammad Omer Aamir ◽  
Nadia Murtaza ◽  
Sadia Naureen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Body Weight ◽  
Kidney Disease ◽  
Recombinant Human Erythropoietin ◽  
Case Series ◽  
Military Hospital ◽  
P Value ◽  
Human Erythropoietin ◽  
Age Range

Objective: To determine the effect of subcutaneous recombinant human erythropoietin on blood pressure in predialysis chronic kidney disease (CKD) patients. Study Design: Case-series descriptive study. Place and Duration of Study: Combined Military Hospital Peshawar, from Mar 2016 to Sep 2016. Methodology: A total of 100 cases were enrolled. Inclusion criteria was patients of 18 to 60 years of both gender & estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 having Hb <10g/dL and pre-dialysis while Exclusion Criteria was pregnancy or lactation, BP more than 140/90 mmHg, patients on Haemodialysis and worsening renal function. Baseline BP, body weight and eGFR of anaemic chronic kidney disease patients were recorded prior to EPO Alpha therapy. Erythropoiesis-stimulating agents (ESAs) i.e. EPO Alpha (50-100 Units/kg thrice or once weekly) was administered subcutaneously. Subsequent blood pressure, body weight and eGFR monitoring was done after 2 and 4 weeks post EPO Alpha injection. Results: Mean age range was 46.71 years with range of 20-60 years, 73 (73%) were male while 27 (27%) werefemales. Mean ± SD for other quantitative variables like eGFR was 23.12 ± 5.28, Hb levels (g/dL) was 8.62 ± 0.85,Weight (kg) was 56.66 ± 6.62 and duration of CKD was 9.87 ± 4.02. Frequency of Hypertension (post EPO) was 2(2%) and p-value was 0.453. Conclusion: We concluded that the frequency of hypertension in pre-dialysis patients with chronic kidney disease (CKD) receiving recombinant human erythropoietin (rhEPo) subcutaneously (SC) in low doses, is very low, so rhEPo can be used subcutaneously......................

A Nutritional Assessment Stage 3 Chronic Kidney Disease

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Kathleen E. Adair ◽  
Jeffery L. Heileson ◽  
Matthew N. Peterson ◽  
Rodney G. Bowden ◽  
Jeffrey S. Forsse
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Body Weight ◽  
Kidney Disease ◽  
Nutritional Assessment ◽  
Multiple Linear Regression Model ◽  
The United States ◽  
Dietary Guidelines ◽  
United States Department ◽  
Dietary Intakes

Objective: Dietary guidelines from the Kidney Disease Outcomes Quality Initiative (KDOQI) and the United States Department of Agriculture (USDA) are advised to individuals with mid-spectrum (stages G3a and G3b) chronic kidney disease (CKD), yet typical diets in individuals with CKD remain understudied. The purpose of this study is to assess the self-reported dietary pattern of subjects with diagnosed mid-spectrum CKD and compare the normal dietary intakes to the KDOQI and USDA recommendations. Methods: A cross-sectional analysis of 20 participants with mid-spectrum CKD (n = 6 male [M]; n = 14 female [F]) was conducted to assess subjects’ self-reported dietary intakes for an average of 5 days. Micro and macronutrient analyses were compared to the KDOQI and USDA guidelines by sex to assess nutrition, and an exploratory stepwise multiple linear regression model was used to identify predictors of poor renal function;p-values were considered significant at the α = 0.05 level. Results: All subjects met the recommended caloric intake, but the average consumptions of protein (F = 0.86 ± 0.29g/kg body weight/day, M = 1.18 ± 0.45g/kg body weight/day), saturated fat (F = 12.17 ± 2.28%, M = 13.86 ± 1.20%), and sodium (F = 3.78 ± 2.51g, M = 4.21 ± 0.39g) were high (p < 0.05 for all). The average fiber intakewas low (F = 13.64 ± 4.09g, M = 14.82 ± 7.28g) as well as folate, vitamins D and K, zinc, and calcium intakes compared with the recommendations (p < 0.05 for all). The only significant contributor to higher renal function in the exploratory regression analysis was male sex (p = 0.035).

scholarly journals Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patricia Rivera ◽  
Catalina Miranda ◽  
Nicole Roldán ◽  
Aaron Guerrero ◽  
Javier Olave ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Young Adults ◽  
Body Weight ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Simple Method ◽  
Renin Angiotensin

AbstractObesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

scholarly journals Clinical efficacy of the selective endothelin A receptor antagonist, atrasentan, in patients with diabetes and chronic kidney disease (CKD)

Life Sciences ◽  
2012 ◽  
Vol 91 (13-14) ◽  
pp. 739-742 ◽  
Author(s):  
Dennis L. Andress ◽  
Blai Coll ◽  
Yili Pritchett ◽  
John Brennan ◽  
Mark Molitch ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Receptor Antagonist ◽  
Clinical Efficacy ◽  
Endothelin A Receptor ◽  
Patients With Diabetes ◽  
Endothelin A
Sign in / Sign up

Export Citation Format

Share Document