scholarly journals Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1156
Author(s):  
Aikaterini Lysitska ◽  
Nikiforos Galanis ◽  
Ioannis Skandalos ◽  
Christina Nikolaidou ◽  
Sophia Briza ◽  
...  

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p < 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p < 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Aikaterini Lysitska ◽  
Nikiforos Galanis ◽  
Ioannis Skandalos ◽  
Eustathios Mitsopoulos ◽  
Nikolaos Antoniadis ◽  
...  

Abstract Background and Aims Recent studies suggest thw possibility of activating immune mechanism in the onset and progression of atherosclerotic disease. The aim of the present study was to evaluate the role of immune mechanisms in the vessel of patients with Chronic Kidney Disease (CKD) and the association with clinical and laboratory indicators of atherosclerosis. Method Patients with CKD stage V, in whom a radiocephalic arteriovenous fistula (RC-AVF) was created, were included in the study. Patients were divided in two groups, group A was consisted of patients who were on stage V, pre-dialysis, and being prepared to start on hemodialysis (HD), and those who had already been on HD for at least 3 years, and were having a new RC-AVF formation, due to previous failure, group B. Inclusion criteria were: age 25-80 years, gradual deterioration of renal function up to stage V or under dialysis for more than 3 years. All patients should have been under close follow up for at least 3 years prior to enrolment, with adequate control of diabetes, hypertension, dyslipidemia, secondary hyperparathyroidism and anemia. The control group included healthy volunteers of similar age, sex and ethnicity, who agreed to have a radial artery biopsy during an orthopedic procedure because of a fracture. All patients were informed and signed the consent form. Patients’ history, primary disease and comorbid conditions, medication and clinical examination were recorded based on hospital outpatients’ files. Prior to the scheduled day of RC-AVF creation, all patients underwent laboratory examination, included hematological and serum biochemical analyses. The histological characteristics, inflammatory activation and immunophenotypic alterations of the radial artery wall were estimated and their association with the severity of calcification and atherosclerosis were studied. Presence and severity of atherosclerotic lesions in CKD patients was assessed based on the measurement of common carotid intima – media thickness (IMT) of the common and internal carotid on both sides. Results Significant correlation was fount between inflammatory infiltration [expression of CD3(+), CD20(+), CD68(+) cells], cellular activation [CD34(+), a-SMA(+) cells] and calcification regulators (MPG, RANKL, OPG) with the degree of vascular calcification, as this was estimated and classified based on Verhoff’s Elastic and von Kossa staining Forty five patients with chronic kidney disease (CKD), stage V, either pre-dialysis (p=25) (group A) or on hemodialysis (HD) (p=20) (group B) were included in the study. There were no significant differences in age, sex, race, and also in the frequency of hypertension, diabetes mellitus or smoking habits between patients and controls. Presence and severity of atherosclerotic lesions in CKD patients was assessed based on the measurement of common carotid intima – media thickness (IMT) of the common and internal carotid on both sides. Conclusion Atherosclerotic disease in Chronic KidnEy Disease and its clinical effects appear to be directly related to inflammatory ifiltration of blood vessels by T, B lymphocytes, macrophages and myofibrolasts, as well as factors that affect calcification.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Can Sevinc ◽  
Gulay Yilmaz ◽  
Sedat Ustundag

Abstract Background and Aims Atherosclerosis and its associated cardiovascular diseases starting from the early stages of chronic kidney disease (CKD) are the most important cause of increased morbi-mortality in the CKD process. In studies performed in patients with end-stage renal disease (ESRD), it is observed that the calcification occured in the vascular structures was an important component of the atero-arteriolosclerosis process. The number of studies investigating the relationship between vascular calcification and the development of atherosclerosis and increased morbi-mortality in the process of CKD are quite small and limited to patients undergoing hemodialysis (HD) treatment for ESRD. We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Method Our study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney patients who did not require dialysis treatment. Thirty-two (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD cases were included. The healthy control group did not have a history of regular use of medication for any reason, known acute or chronic disease. Chronic kidney disease group, with no acute disease, no history of known malignancy and cerebrovascular disease. The patients' GFR was also calculated with CKD-EPI Formula. The mean carotid artery intima media thickness was calculated by dividing the sum of right and left carotid artery intima media thickness. Statistical analysis was performed with IBM SPSS Statistics 20.0.0. Results The laboratory data of the healthy control group, stage 2 CKD group, stage 3 CKD group, stage 4 CKD group and stage 5 CKD groups were statistically compared with the healthy control group, between themselves and the whole CKD group, the results were given in Table-1. Chronic kidney disease group divided into two groups; carotid artery intima media thickness less than 0.750 millimeters (without subclinical atherosclerosis) and those above 0.750 millimeters (with subclinical atherosclerosis). The mean C-IMT, CRP, FETUIN-A, OPG and MGP of the two groups were compared statistically and the results are shown in Table-2. In chronic kidney patients, age (r = 0.493, p &lt;0.001), BMI (r = 0.337, p = 0.001), CRP (r = 0.301, p = 0.004), TG (r = 0.245, p = 0.019 ), urea (r = 0.228, p = 0.029), SBP (r = 0.212, p = 0.043), fasting blood sugar (r = 0.212, p = 0.043) have positive linear relationship, fetuin-A (r = -0.409, P = 0.001), OPG (r = -0.235, p = 0.024), GFR (r = -0.209, p = 0.046) have a negative linear relationship with CIMT. The multiple relationships between CIMT and other variables are given in Table-3. The mean CIMT (r =-0.417, p = 0.001), right CIMT (r = -0.412, p = 0.001), left CIMT (r = -0.410, p = 0.001), urea (r = -353, p = 0.007), CRP (r = -0.322, p = 0.014), UPE (r = -0.301, p = 0.022), creatinine (r = -0.277, p = 0.035), age (r = -0.262, p = 0.047) show a negative linear relationship with Fetuin-A. Multiple relationships between fetuin-A and other variables are given in Table-4. Conclusion Our study shows that; In particular, fetuin-A levels, which is a vascular calcification inhibitor, begin to decline from the early stages of CKD and is significantly lower in patients with atherosclerosis. This suggests that fetuin-A may be used as an early marker in CKD with increased cardiovascular mortality. On the other hand, contradictions related to the levels of OPG and MGP in CKD and its role in the development of atherosclerosis continue. The results in our study also support this situation. Reducing mortality and morbidity in CKD primarily depends on reducing the risk of cardiovascular events. Pre-recognition of these risks is important, so large-scale studies on vascular calcification inhibitors are needed.


Author(s):  
Adhi Permana ◽  
Ian Effendi ◽  
Taufik Indrajaya

Chronic kidney disease is associated with a high mortality rate, especially cardiovascular disease associated with mineral and bone disorders. Sclerostin is an inhibitor of Wnt signaling which has the effect of increasing the occurrence of vascular calcification in patients with chronic kidney disease. There are several studies that show different results. Carotid intima media thickness ultrasound examination is a tool to identify atherosclerosis which is part of vascular calcification. The aim of this study is to look at the correlation of sclerostin with carotid intima media thickness (CIMT) in patients with chronic kidney disease undergoing hemodialysis. In this cross section, the concentration of sclerostin was measured by examination of enzymed linked immunosorbent assay. CIMT measurement by ultrasound mode B examination. There were 40 patients in this study. The mean sclerostin level was 256.68 ± 127.76 pg / ml. Sclerostin levels are declared high if above 162 pg / ml there are 30 people. CIMT thickening was present in 11 patients. There was no significant correlation of serum sclerostin with CIMT in patients with chronic kidney disease undergoing hemodialysis (r-0.32 p0,847). In multivariate linear regression, hemodialysis duration is an independent factor that is significantly significant with CIMT. There was no significant correlation of serum sclerostin with CIMT in patients with chronic kidney disease undergoing hemodialysis.


2020 ◽  
Vol 71 (6) ◽  
pp. 194-204
Author(s):  
Teim Baaj ◽  
Ahmed Abu-Awwad ◽  
Mircea Botoca ◽  
Octavian Marius Cretu ◽  
Elena Ardeleanu ◽  
...  

Organ damages, which contribute to the overall cardiovascular risk of hypertensive patients, should be early detected, prevented and treated. The study evaluated organ damage in a hypertensive study group with chronic kidney disease (CKD), compared with a study group of hypertension without CKD. Albuminuria was present in 41.2% and reduced estimated glomerular filtration rate [60 ml/min/m2 was present in 72.5% of hypertensive with CKD. The comparison of organ damage revealed in the CKD group a statistical significant higher prevalence of organ damage as follows: intima-media thickness ]0.9 mm in 39.9% vs 10.5%, carotid plaques in 28.2% vs 12.6%, left ventricular hypertrophy in 39.9% vs 31%, ankle brachial index in 6.2% vs 3.5%. Early detection and treatment of additional cardiovascular risk factors as dyslipidaemia and hyperglycaemia, that have significant role in the pathogenesis of organ damage, contribute to the better prevention of cardiovascular and renal complications in hypertension with CKD.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Saleiro ◽  
D De Campos ◽  
J Lopes ◽  
R Teixeira ◽  
J.P Sousa ◽  
...  

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease. Aim To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS). Methods 355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months. Results Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction &lt;40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome. Conclusion The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beata Sieklucka ◽  
Tomasz Domaniewski ◽  
Marta Zieminska ◽  
Malgorzata Galazyn-Sidorczuk ◽  
Anna Pawlak ◽  
...  

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.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Andrea Zatelli ◽  
Marco Pierantozzi ◽  
Paola D'Ippolito ◽  
Mauro Bigliati ◽  
Eric Zini

Chitosan and alkalinizing agents can decrease morbidity and mortality in humans with chronic kidney disease (CKD). Whether this holds true in dog is not known. Objective of the study was to determine whether a commercial dietary supplement containing chitosan, phosphate binders, and alkalinizing agents (Renal), compared to placebo, reduces mortality rate due to uremic crises in dogs with spontaneous CKD, fed a renal diet (RD). A masked RCCT was performed including 31 azotemic dogs with spontaneous CKD. Dogs enrolled in the study were randomly allocated to receive RD plus placebo (group A; 15 dogs) or RD plus Renal (group B; 16 dogs). During a first 4-week period, all dogs were fed an RD and then randomized and clinically evaluated up to 44 weeks. The effects of dietary supplements on mortality rate due to uremic crises were assessed. At 44 weeks, compared to group A, dogs in group B had approximately 50% lower mortality rate due to uremic crises (P=0.015). Dietary supplementation with chitosan, phosphate binders, and alkalinizing agents, along with an RD, is beneficial in reducing mortality rate in dogs with spontaneous CKD.


2021 ◽  
pp. 1-10
Author(s):  
Dai Deng ◽  
Xue Han ◽  
Zongli Diao ◽  
Wenhu Liu

<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.


2020 ◽  
Vol 71 (01) ◽  
pp. 8-11
Author(s):  
BOGDAN ALEXANDRU VIȚĂLARU ◽  
MĂDĂLIN ION RUSU ◽  
CARMEN MIHAI ◽  
ALEXANDRU CHIOTOROIU

Catheters designed for chronic peritoneal dialysis have Dacron cuffs meant to protect the patient against bacterialinfection and catheter migration that may lead to a high peritonitis rate in case of extensive use. Peritoneal catheter isfixed by suturing the skin with a non-absorbable monofilament thread ranging from 4/0 to 2/0. The two types of suturesmost commonly used are Roman sandal and Chinese fingertrap. In this study we selected 44 dogs, both males andfemales with CKD (Chronic Kidney Disease) undergoing peritoneal dialysis. We have created two groups: first group(A) of 22 patients were treated using a peritoneal catheter for chronic treatment, with Roman sandal suture and thesecond group of 22 patients (B) were treated using a peritoneal catheter for chronic treatment, with Chinese fingertrapsuture. All patients from group A kept the catheters until the end of the treatment (22 out of 22, 100%). Eight out of14 patients (36.36%) from group B needed secondary suture. Four out of the eight patients (18.18%) form the group Bneeded secondary suturing because of the suture weakening. Three out of the eight patients (13.63%) form the groupB needed secondary suturing of the catheter because of the skin rupture at the initial placement spot of the suture. Oneof the eight patients (4.54%) form the group B needed secondary suturing of the catheter because of the catheterreplacement, due to the weakening of the suture and its lack of resistance to the aggression manifested by the patients


2019 ◽  
Vol 2 (1) ◽  

Background: The purpose of the present study was to retrospectively evaluate the subacute or late toxicities in the kidney, lung, and liver after two total body irradiation regimens, 12 Gy in 6 fractions (group A) and 12 Gy in 4 fractions (group B). Methods: Forty-two patients who underwent total body irradiation (group A, n=32; group B, n=10) between June 1997 and June 2013 were included in the present study. The median follow up period was 60 months (range: 3–219 months) for the patients in group A and 143 months (range: 5–220 months) for the patients in group B. We evaluated the renal, pulmonary, and hepatic toxicities using the Common Terminology Criteria for Adverse Events version 4.0. Results: There were 4 cases of chronic kidney disease (group A, n=1; group B, n=3). Although the cumulative incidence of chronic kidney disease differed significantly between the two total body irradiation regimens (p=0.014), the pulmonary and hepatic toxicities did not differ to a statistically significant extent. Conclusion: The present study suggests that a higher dose per fraction caused a higher incidence of chronic kidney disease.


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