Relationship between Microfibrillar-Associated Protein 4 Levels and Subclinical Myocardial Damage in Chronic Kidney Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 257-265
Author(s):  
Sonat Pınar Kara ◽  
Gülsüm Özkan ◽  
Demet Özkaramanlı Gür ◽  
Gaye Kübra Emeksiz ◽  
Ahsen Yılmaz ◽  
...  

Introduction: Chronic kidney disease (CKD) is a widespread health problem, in which mortality is most frequently due to cardiovascular diseases. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. MFAP4 is involved in several biological processes, particularly the maintenance of vascular integrity and extracellular matrix remodeling. Our review of the literature revealed no data concerning MFAP4 levels in CKD and its relationship with myocardial functions. Objective:The purpose of this study was therefore to investigate MFAP4 levels in CKD, parameters affecting these, and the relationship with myocardial functions. Materials and Methods: Seventy-nine CKD patients and 30 healthy controls were included in the study. Routine biochemical tests and echocardiography were performed once demographic data had been recorded. Blood specimens were collected for MFAP4 analysis, and the results were subjected to statistical analysis. Results: MFAP4 levels were significantly higher in the patient group than in the control group (p< 0.001). Doppler parameters revealed more frequent LV diastolic impairment in the patient group. Tissue Doppler systolic velocity and global longitudinal strain were significantly impaired, revealing the subclinical LV systolic dysfunction in CKD patients. MFAP4 elevation in the patient group was positively correlated with aortic root (AR), global circumferential strain (GCS), and GCS rate. Conclusion: Our results showed MFAP4 elevation in CKD for the first time in the literature, and that this elevation may be related to GCS and AR dilation. We think that, once supported by further studies, MFAP4 may constitute a marker in the evaluation of myocardial functions in CKD.

Author(s):  
Farhana Yasmin ◽  
Shireen Afroz

Background: Patients with Chronic Kidney Disease (CKD) are at significantly increased risk for both morbidity and mortality from cardiovascular disease (CVD). Determining the spectrum of echocardiographic abnormalities in these patients can help in reduction of morbidity and mortality from CKD. Materials and Methods: This cross-sectional study was held on department of Pediatric Nephrology, Dhaka Shishu Hospital, Dhaka, during July 2018 to December 2018 (Six months). A total of thirty-six children with chronic kidney disease with creatinine clearance <60ml/min/1.73 m2 and age ranged from 2 to 16 years on supportive treatment and hemodialysis were included. In control group equal number of age and sex matched healthy children without any preexisting renal or cardiovascular diseases were included. Both study group and control group were assessed for cardiovascular findings by echocardiography. Results: The mean age was 9.09±3.01 years (mean±SD) in case group and 7.85±3.69 years (mean±SD) in control group. Regarding sex, 22 patients (61.1%) in the case group were male and 14 (38.9%) were female.  In this study, in CKD patients significant (p<0.001) difference was observed in following cardiac parameters, left ventricular end diastolic diameter (LVEDD) (38.34 vs 34.52), left ventricular end systolic diameter LVESD (26.64 vs 20.75), interventricular septal thickness (IVS) (9.34 vs 7.27), left ventricular posterior wall thickness (LVPWT) (8.36 vs 7.46), ejection fraction (EF) (56.68% vs 70.36%), fractional shortening (FS) (31.88% vs 38.30%) and peak early diastole velocity/peak atrial filling velocity (E/A ratio) (1.15 vs 1.45) when compared to control group. Most common cardiac abnormality in children with chronic kidney disease were left ventricular systolic dysfunction (44.4%), mild pulmonary hypertension (30.6%) and left atrial dilatation (27. 8%). Conclusion: Left ventricular systolic dysfunction was the commonest echocardiographic findings in CKD children. There was also significant difference in diastolic function between study and control group.


2020 ◽  
Vol 5 (1) ◽  
pp. e10-e10
Author(s):  
Zebunnesa Zeba ◽  
Kaniz Fatema ◽  
Ahmed Faisal Sumit ◽  
Rahelee Zinnat ◽  
Liaquat Ali

Introduction: Early identification of chronic kidney disease (CKD) provides valuable opportunities for effective interventions that reduce the risk of outcomes, particularly renal failure. Objectives: This study aimed to screen the Bangladeshi asymptomatic adult population for CKD to identify potential risk factors for its development. Patients and Methods: The screening program was carried out among the 400 subjects in the Thakurgaon district of Bangladesh to identify people with the risk of CKD. All the subjects were asymptomatic and previously been never diagnosed with kidney diseases. Demographic data were collected by a structured questionnaire. Urinary protein was tested by dipstick method, and serum creatinine was measured by an auto-analyzer. Estimated glomerular filtration rate (eGFR) was calculated by using standard formula. CKD was diagnosed and classified according to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. Results: A total of 18.2% respondents were found to have likely CKD to whom 82% were in stage 1 and 18% were in stage 2. The majority of the likely CKD respondents (30.1%) were in age >60 years. The prevalence of proteinuria was significantly (P=0.0001) higher among previously documented CKD patients compared to the control group. Logistic analysis revealed that after adjustments, CKD showed a significant association with diabetes mellitus (ORs: 7.46, P=0.00), smoking (ORs: 2.36, P=0.02), obesity (ORs: 3.98, P=0.00) and hypertension (ORs: 1.16, P=0.66) compared to control. Conclusion: A substantial number of adults were found to be unaware of the existence of CKD hence, large-scale prevention programs should be undertaken to reduce the classical risk factors of these disorders.


2005 ◽  
Vol 18 (6) ◽  
pp. 727-731 ◽  
Author(s):  
Cidônia de Lourdes Vituri ◽  
Márcio Alvarez-Silva ◽  
Andréa Gonçalves Trentin ◽  
Vera Lúcia Cardoso Garcia Tramonte ◽  
Primavera Borelli

OBJECTIVE: The objective of the present study was to measure the concentration of bone marrow extracellular matrix thrombospondin in mice, following hypoplasia induced by protein malnutrition. METHODS: Two-month-old male Swiss mice were submitted to protein malnutrition by way of a low-protein diet containing 4.0% casein until they lost 20.0% of their original body weight, while the control group mice were fed 14.0% casein for 15 days. The bone marrows of the animals were aspirated and transferred to phosphate-buffered saline tubes for extraction. The extracellular matrix protein was analyzed by 7.5% SDS-PAGE and thrombospondin by Enhanced Chemiluminescence Light Western blotting. RESULTS: The amount of thrombospondin was 30% higher in the undernourished samples when compared to the control samples. CONCLUSION: This study suggests that the hypoplasia induced by protein malnutrition probably alters the functioning of the bone marrow microenvironment resulting in a higher thrombospondin concentration.


2018 ◽  
Vol 38 (2) ◽  
pp. 255-266 ◽  
Author(s):  
M Sözmen ◽  
AK Devrim ◽  
YB Kabak ◽  
T Devrim

Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.


2021 ◽  
Author(s):  
Yuen Tan ◽  
Qingchuan Chen ◽  
Xing Yao ◽  
Chao Zhang ◽  
Siwei Pan ◽  
...  

Background Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. This study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC. &#160;Methods The expression, overall survival and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas(TCGA)database, respectively. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes.&lt;/p&gt; &#160;Results COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was upregulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.&lt;/p&gt; &#160;Conclusion COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.


2010 ◽  
Vol 298 (3) ◽  
pp. R815-R823 ◽  
Author(s):  
L. G. Bongartz ◽  
B. Braam ◽  
M. C. Verhaar ◽  
M. J. Cramer ◽  
R. Goldschmeding ◽  
...  

Left ventricular systolic dysfunction (LVSD) in patients with chronic kidney disease (CKD) is associated with poorer prognosis. Because patients with CKD often exhibit progressively decreased nitric oxide (NO) availability and inhibition of NO production can reduce cardiac output, we hypothesized that loss of NO availability in CKD contributes to pathogenesis of LVSD. Subtotally nephrectomized (SNX) rats were treated with a low dose of the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA; 20 mg/l water; SNX+l-NNA) and compared with relevant control groups. To study permanent changes separate from hemodynamic effects, l-NNA was stopped after week 8 and rats were followed up to week 15, until blood pressure was similar in SNX+l-NNA and SNX groups. To study effects of NO depletion alone, a control group with high-dose l-NNA (l-NNA-High: 100 mg/l) was included. Mild systolic dysfunction developed at week 13 after SNX. In SNX+l-NNA, systolic function decreased by almost 50% already from week 4 onward, together with markedly reduced whole body NO production and high mortality. In l-NNA-High, LVSD was not as severe as in SNX+l-NNA, and renal function was not affected. Both LVSD and NO depletion were reversible in l-NNA-High after l-NNA was stopped, but both were persistently low in SNX+l-NNA. Proteinuria increased compared with rats with SNX, and glomerulosclerosis and cardiac fibrosis were worsened. We conclude that SNX+l-NNA induced accelerated and permanent LVSD that was functionally and structurally different from CKD or NO depletion alone. Availability of NO appears to play a pivotal role in maintaining cardiac function in CKD.


2015 ◽  
Vol 1 (3) ◽  
pp. 92-95 ◽  
Author(s):  
Niki Prakoura ◽  
Panos Kavvadas ◽  
Christos Chatziantoniou

Abstract Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors. The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.


2020 ◽  
Vol 26 (4) ◽  
pp. 3481-3484
Author(s):  
Anna Nenova-Nogalcheva ◽  
◽  
Desislava Konstantinova ◽  
Petia Pechalova ◽  
◽  
...  

Dentists usually recommend at least two minutes of brushing two times per day as a minimum. The purpose of this study is to establish the frequency of teeth brushing for patients with terminal stage of chronic kidney disease and for healthy controls. Materials and methods: 140 patients from Northeastern Bulgaria took informed participation, volunteering, in this study. They are separated into two groups – 70 people were diagnosed with terminal stage of chronic kidney disease (CKD) and chroniohemodialysis at different stages of disease duration and 70 healthy controls. Anamnestic and socio-demographic data were collected, about gender, age and frequency of teeth brushing. The result was statistically processed using the IBM SPSS Statistics software, Version 20. Results: Data show that there is a statistically significant difference (χ2 = 79,031, p=0,000 ) between the patients of the groups studied. As we have expected, the patients from the control group brush their teeth more often (between 2 and 3 times per day). The Mann-Whitney test with Bonferroni correction shows that the CKD patients brush their teeth daily less than the people from the control group. Statistically significant difference (U = 1831,000, р = 0,004) is established between the two group participants. Conclusion: The frequency of teeth brushing as a main factor for maintaining good personal oral hygiene is higher for the healthy controls in comparison to the patients under the study, who belong to the group of people with CKD. We need more studies in order to understand better how could the frequency of teeth brushing influence the limitation of oral problems for people with kidney diseases on chroniodialysis.


2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

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