scholarly journals P0690CORRELATIONS BETWEEN OPG/RANKL/RANK AXIS, VITAMIN D STATUS, PTH AND VASCULAR CALCIFICATION IN AN ADENINE-INDUCED MODEL OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beata Sieklucka ◽  
Tomasz Domaniewski ◽  
Marta Zieminska ◽  
Malgorzata Galazyn-Sidorczuk ◽  
Anna Pawlak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Control Group ◽  
Urea Nitrogen ◽  
And Control ◽  
Rank Gene

Abstract Background and Aims Chronic kidney disease (CKD) is a major public health problem worldwide and refers to a wide range of disorders in bone and mineral metabolism, abnormalities of biochemical parameters and pathological calcification of the blood vessels. Vascular calcification (VC) is a common complication in CKD patients, contributes to cardiovascular disease (CVD), and associates with increased mortality and morbidity. The precise mechanism of VC in CKD is not yet fully understood. Recently discovered molecules such as osteoprotegerin (OPG), its ligand receptor activator of nuclear factor NF-κB ligand (RANKL) and RANK are not only well-known to play a crucial role in bone homeostasis, but they has also been implicated in the process of development of vascular complications However the exact role of OPG/RANKL/RANK axis in the process of VC has not been yet fully assessed. Thus, the aim of this work is to evaluate the role of OPG/RANKL/RANK axis in the process of calcification in CKD. Method Seventy two male Wistar rats weighing 260-290 g (8-weeks old) were initially divided into 6 groups containing 12 animals in each group. Rats were divided into six groups: control rats (K4, K6, K8) and CKD rats (B4, B6, B8). Control group rats received standard diet, whereas CKD rats were fed a low adenine – diet containing 0.3 % adenine, 1.0 % Ca, 1.2 % Pi through 4 (K4, B4), 6 (K6, B6) and 8 (K8, B8) weeks. Subsequently, CKD and control rats were sacrificed at weeks 4 (n=24), 6 (n=24) and 8 (n=24). One day before being killed, the rats were placed in metabolic cages for 24-hour urine collection. Thereafter, the rats were anesthetized and samples of blood, as well as aortas were collected. Next, the OPG, RANKL, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D3 1,25(OH)2D3 concentrations were determined using appropriate ELISA kits. Then the sRANKL/OPG ratio was calculated. The OPG, RANK and RANKL gene expression was assessed using real-time PCR (RT-PCR). The VC was quantified by measurement of the arterial calcium (Ca) and phosphate (Pi) content using flame atomic absorption. Serum levels of urea nitrogen, creatinine, uric acid, Ca, Pi and urinary levels of creatinine, Ca and Pi were measured. Results There was a progressive increase in serum urea nitrogen, creatinine, uric acid and PTH of CKD rats in comparison to control values. We also observed significantly decreased levels of 25(OH)D, 1,25(OH)2D and serum Ca. Total Ca content in the aorta was significantly increased in CKD rats in comparison with control group, whereas total Pi content in the aorta was significantly increased only in B8 group in comparison to appropriate controls. There were no differences in serum OPG and sRANKL levels between CKD and control rats. In contrast, we observed decreased OPG, RANKL and RANK gene expression in a B4 group in comparison to appropriate controls, whereas in a B6 group we noticed increased OPG, RANKL and decreased RANK gene expression. B8 group revealed increased RANKL and RANK gene expression, but there were no differences in OPG gene expression between CKD rats and control group. Furthermore, we observed positive correlations between serum sRANKL and OPG and RANK gene expression. Ca and P content in the aorta inversely corelated with RANKL gene expression, whereas positively with OPG gene expression. Serum 25(OH)D concentrations correlated inversely with Ca in aorta. PTH was positively correlated with serum RANKL and OPG and gene expression these cytokines. Conclusion Our results suggest that OPG/RANK/RANKL axis may be involved in the process of vascular calcification in chronic kidney disease. However, its role and evaluation of precise mechanism in this field requires further evaluation.

scholarly journals Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Loïc Louvet ◽  
Laurent Metzinger ◽  
Janine Büchel ◽  
Sonja Steppan ◽  
Ziad A. Massy
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Inorganic Phosphate ◽  
Time Course ◽  
Mechanistic Explanation ◽  
High Phosphate

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

scholarly journals Effect of Allopurinol in Chronic Kidney Disease Progression in Asymptomatic Hyperuricaemic Subjects

2017 ◽  
Vol 25 (1) ◽  
pp. 5-15
Author(s):  
ASM Tanim Anwar ◽  
Md Nizamuddin Chowdhury ◽  
Md Nazrul Islam ◽  
Parvez Iftekher Ahmed ◽  
Sohely Ahmed Sweety ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Treatment Group ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Chronic Kidney Disease Stage ◽  
Disease Stage ◽  
Control Group ◽  
And Control

This was a hospital based prospective, interventional study which included CKD stage 3- 5 patients with higher level of uric acid (male>7mg/dl, female>6mg/dl). The objective of the study was to evaluate the effect of allopurinol in chronic kidney disease (stage 3-5) progression in asymptomatic hyperuricaemic patients.One hundred and twenty patients were distributed in two groups. Sixty patients were placed in treatment group and sixty in control group. Purposive sampling technique was followed. In the study mean age was 49 (±9) years in treatment group and 45 (±11) years in control groups. Male were predominant in both groups. There were no significant difference in baseline characteristics between treatment group and control group (p>0.05). Sixty patients of treatment group were administered a dose of 100 mg/d of allopurinol. Follow up assessment was done at basally, at 4 months and at 8 month after starting treatment. No significant differences were seen between baseline SBP, DBP, Hb and HbA1c with 4th month and 8th month follow up in both treatment group and control group, but mean Hb was significantly decreased in control group from the baseline after 8 month. Serum uric acid was decreased in treatment group while it was significantly raised from the base line at 4th month and 8th month in control group. In treatment group serum creatinine was decreased and eGFR was raised from the baseline after 8 month. On the other hand, in control group serum creatinine was significantly raised and eGFR was significantly decreased from the baseline at 8th month. While comparing between two groups results showed means of serum uric acid was significantly decreased in treatment group compared to control group after 8th month. There was a negative correlation between Uric Acid with eGFR after 8 month of allopurinol treatment although this finding was not statistically significant. So, allopurinol may have a protective role in CKD progression by decreasing serum uric acid level in patients with chronic kidney disease stage 3 - 5 with asymptomatic hyperuricaemia.J Dhaka Medical College, Vol. 25, No.1, April, 2016, Page 5-15

scholarly journals Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm

2019 ◽  
Author(s):  
Milena Miszczuk ◽  
Verena Müller ◽  
Christian E. Althoff ◽  
Andrea Stroux ◽  
Daniela Widhalm ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Strong Association ◽  
Renal Cysts ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Abdominal Aortic ◽  
And Control ◽  
Charité Berlin

AbstractAbdominal aortic aneurysms (AAA) primarily affect elderly men who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. Two groups of patients (100/group), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. SRC (73% vs. 57%; p<0.001) and CKD (31% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

scholarly journals Effect of Allopurinol on Inflammatory Markers in Chronic Kidney Disease Patients with Asymptomatic Hyperuricaemia

2017 ◽  
Vol 26 (1) ◽  
pp. 12-24
Author(s):  
ASM Tanim Anwar ◽  
Md Nizamuddin Chowdhury ◽  
Md Nazrul Islam ◽  
Parvez Iftekher Ahmed ◽  
Sohely Ahmed Sweety ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Treatment Group ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Chronic Kidney Disease Stage ◽  
Disease Stage ◽  
Control Group ◽  
Base Line

This was a hospital based prospective, interventional study which included CKD stage 3- 5 patients with higher level of uric acid (male>7mg/dl, female>6mg/dl). The objective of the study was to evaluate the effect of allopurinol on inflammatory markers in patients with chronic kidney disease (stage 3-5) with asymptomatic hyperuricaemia. One hundred and twenty patients were distributed in two groups. Sixty patients were placed in treatment group and sixty in control group. Purposive sampling technique was followed. In the study mean age was 49 (±9) years in treatment group and 45 (±11) years in control groups. Male were predominant in both groups. There were no significant difference in baseline characteristics between treatment group and control group (p>0.05). Sixty patients of treatment group were administered a dose of 100 mg/d of allopurinol. Follow up assessment was done at basally, at 4 months and at 8 month after starting treatment. No significant differences were seen between baseline SBP, DBP, Hb and HbA1c with 4th month and 8th month follow up in both treatment group and control group, but mean Hb was significantly decreased in control group from the baseline after 8 month. No significant change was found in case of mean ESR at 4th and 8th month in any group. But base line mean CRP was significantly reduced in treatment group and increased in control group at 4th and 8th month of follow up. Serum uric acid was decreased in treatment group while it was significantly raised from the base line at 4th month and 8th month in control group. While comparing between two groups results showed means of serum uric acid and CRP were significantly decreased in treatment group compared to control group after 8th month. There was a positive correlation between Uric Acid with CRP level after 8 month of allopurinol treatment although this finding was not statistically significant. So, allopurinol may have a protective role in CKD by decreasing serum uric acid level and reduction of inflammatory response in patients with chronic kidney disease stage 3 - 5 with asymptomatic hyperuricaemia.J Dhaka Medical College, Vol. 26, No.1, April, 2017, Page 12-24

scholarly journals Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling

2016 ◽  
Vol 9 (3) ◽  
pp. 444-453 ◽  
Author(s):  
Vibha Bhatnagar ◽  
Erin L. Richard ◽  
Wei Wu ◽  
Caroline M. Nievergelt ◽  
Michael S. Lipkowitz ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Potential Role

scholarly journals Association between MANBA Gene Variants and Chronic Kidney Disease in a Korean Population

2021 ◽  
Vol 10 (11) ◽  
pp. 2255
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Kidney Function ◽  
Linear Regression Analysis ◽  
Public Health Problem ◽  
Minor Allele ◽  
Gene Variants ◽  
Global Public Health

Chronic kidney disease (CKD), a damaged condition of the kidneys, is a global public health problem that can be caused by diabetes, hypertension, and other disorders. Recently, the MANBA gene was identified in CKD by integrating CKD-related variants and kidney expression quantitative trait loci (eQTL) data. This study evaluated the effects of MANBA gene variants on CKD and kidney function-related traits using a Korean cohort. We also analyzed the association of MANBA gene variants with kidney-related traits such as the estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN), creatinine, and uric acid levels using linear regression analysis. As a result, 14 single nucleotide polymorphisms (SNPs) were replicated in CKD (p < 0.05), consistent with previous studies. Among them, rs4496586, which was the most significant for CKD and kidney function-related traits, was associated with a decreased CKD risk in participants with the homozygous minor allele (CC), increased eGFR, and decreased creatinine and uric acid concentrations. Furthermore, the association analysis between the rs4496586 genotype and MANBA gene expression in human tubules and glomeruli showed high MANBA gene expression in the minor allele carriers. In conclusion, this study demonstrated that MANBA gene variants were associated with CKD and kidney function-related traits in a Korean cohort.

scholarly journals Study of serum homocysteine level in patients with chronic kidney disease and its association with renal function and serum albumin

2020 ◽  
Vol 8 (6) ◽  
pp. 2195
Author(s):  
Vandana Yadav ◽  
Vivek Prakash ◽  
Bushra Fiza ◽  
Maheep Sinha
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Serum Albumin ◽  
Control Group ◽  
Serum Homocysteine ◽  
The Mean ◽  
Gandhi Medical College ◽  
And Control

 Background: Chronic kidney disease (CKD) includes irreversible destruction of nephrons leading to progressive decline in glomerular filtration rate. A preferential defect in Homocysteine disposal could hypothetically occur in CKD and subsequently lead to hyperhomocysteinemia. Understanding the status of Homocysteine and other parameters in CKD is useful in the management of the disease. Objective of the study is to estimate serum Homocysteine in CKD patients and its association with renal function and serum albumin in patients with CKD.Methods: The study design involves hospital based observational comparative study. The study was conducted in Department of Biochemistry in association with Department of Nephrology of Mahatma Gandhi Medical College and Hospital, Jaipur between May 2017 to June 2018. 100 diagnosed patients of CKD, visiting the Outpatient Department of Nephrology were enrolled as cases for the study. Patients having cardiovascular disease, Chronic liver disease, Age more than 60 years and pregnant females were excluded from study. The control group consists of 100 age and sex matched healthy individuals.Results: The mean serum creatinine levels of case and control group were 7.50±3.74 mg% and 0.83±0.22 mg% respectively. The mean of serum homocysteine levels of subject group was 27.35±12.52 µmol/L while the mean serum homocysteine levels of control group was 11.06±3.52 µmol/L. The serum homocysteine levels were significantly higher in the CKD patient group. The serum level of albumin in CKD patients and control group were 2.86±0.86 g/dl and 4.10±0.58 g/dl respectively. A positive correlation was found between serum creatinine and serum homocysteine levels. A negative correlation between serum homocysteine and serum albumin was found.Conclusions: Findings of the present study exhibit that serum homocysteine levels are elevated in CKD in comparison to healthy controls and it is positively correlated with serum creatinine level.

scholarly journals Secreted Frizzled-Related Protein 5 Ameliorates Vascular Calcification in a Rat Model of Chronic Kidney Disease through the Wnt/β-Catenin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Dai Deng ◽  
Xue Han ◽  
Zongli Diao ◽  
Wenhu Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Rat Model ◽  
In Vitro Study ◽  
Calcium Content ◽  
Control Group ◽  
Related Protein ◽  
High Phosphate

<b><i>Introduction:</i></b> Vascular calcification (VC) is highly prevalent and a major cardiovascular risk factor in chronic kidney disease (CKD) patients. Secreted frizzled-related protein 5 (SFRP5), an inhibitor of the Wnt pathway, is an adipokine with a positive effect on metabolic and cardiovascular diseases. Our previous in vitro study showed that SFRP5 attenuates high phosphate-induced calcification in vascular smooth muscle cells by inhibiting the Wnt/β-catenin pathway. Therefore, we hypothesized that SFRP5 may protect against CKD-associated VC (CKD-VC) through the same signalling. <b><i>Methods:</i></b> The rat model of CKD with VC was induced by 0.75% adenine combined with 1.8% high phosphate diet, which were administered with adenovirus vectors of SFRP5. We evaluated the SFRP5 effect on VC by von Kossa staining and calcium content analysis and osteogenic markers by immunohistochemistry and Western blot. The components of Wnt/ß-catenin signalling were also evaluated. <b><i>Results:</i></b> SFRP5 local and serum levels were significantly decreased in the CKD-VC rat model compared with the control group. Adenovirus-mediated overexpression of SFRP5 significantly inhibited VC, which was due to suppression of CKD-induced expression of calcification and osteoblastic markers. Additionally, SFRP5 abrogated activation of the Wnt/β-catenin pathway that plays a major role in the pathogenesis of VC. The specificity of SFRP5 for inhibition of VC was confirmed using an empty adenovirus as a control. <b><i>Conclusion:</i></b> Our results suggest that SFRP5 ameliorates VC of CKD rats by inhibiting the expression of calcification and osteoblastic markers as well as the Wnt/β-catenin pathway. Collectively, this study suggests that SFRP5 is a potential therapeutic target in CKD-VC.

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