scholarly journals EVALUATION OF INFLAMMATION AND ENDOTHELIAL DYSFUNCTION BIOMARKERS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS IN SOKOTO, NIGERIA

2021 ◽  
Vol 1 (1) ◽  
pp. 1-9
Author(s):  
C. A. Otitolaiye ◽  
D. M. Sahabi ◽  
A. M. Makusidi ◽  
Y. Saidu ◽  
L. S. Bilbis

Inflammation and endothelial dysfunction have been known to be involved in the pathogenesis of cardiovascular diseases. As such, examining the levels of inflammation and endothelial dysfunction is very critical to the prevention of cardiovascular diseases among chronic kidney disease (CKD) patients. This study aimed to investigate the progression of inflammation and endothelial dysfunction among CKD patients in Sokoto. A total of 67 CKD patients were divided into 5 groups based on the stages of their kidney disease calculated using the MDRD 4-variable equation for estimated glomerular filtration rate (eGFR). The presence of inflammation was determined by C-Reactive Protein (CRP) and Tumor Necrosis Factor alpha, while endothelial dysfunction was determined by the levels of Asymmetric dimethylarginine (ADMA) using ELISA kits. The mean eGFR of the patients was 49.97 ± 4.69 ml/min/1.73m2. There was significant increase (p<0.05) in CRP, TNF-α and ADMA of the CKD patients across the stages as compared to the non-CKD subjects. It was observed that as the CRP, TNF-α and ADMA increase, the eGFR significantly (p<0.05) decreases. Both CRP and TNF-α indicated a significantly positive correlation (p<0.05) with ADMA. The results indicated progressive increase in inflammation and endothelial dysfunction as CKD deteriorates. In addition, increased levels of inflammation could directly affect endothelial dysfunction, thereby aggravating cardiovascular morbidity and mortality among CKD patients in Sokoto. Otitolaiye, C. A. | Department of Biochemistry, Sokoto State University, Sokoto, Nigeria

Author(s):  
Sanjay Srinivasa ◽  
Santhosh K. Madhusudhan

Background: Chronic Kidney Disease (CKD) is one of the major health disorders associated with significant morbidity and mortality. This was a 6 week’s interventional study of orally administered, symbiotic supplement (probiotic with prebiotic) in stage 5D patients of chronic kidney disease (CKD) on twice a week hemodialysis. The objective was to look for safety of symbiotics (Nitrophage ForteTM) and for its anti-inflammatory effects measured by serum hsCRP (Highly specific C reactive protein), IL-6 (Interleukin- 6) and TNF-α (Tumour Necrosis Factor- α) levels. This translating to improvement in the Quality of life (QOL) assessed using SF-36 QOL questionnaire and Subjective Global Assessment (SGA) scoring. Methods: Subjects on twice a week dialysis for at least 3 months were included. Parameters at baseline (representing previous 3 months) were compared to that at the end of treatment. Oral supplementation of strain specific and unique composition of symbiotic sachet supplementation were administered twice daily containing Lactobacillus acidophilus 400mg, Bifidobacterium longumm 400mg, Streptococcus thermophilus with Fructooligosaccharide 100mg adding to 1 gram was given for 6 weeks.Results: 38 patients out of total 48 enrolled completed the study. Symbiotic therapy was found to be well tolerated with no significant adverse effects. 60.52%, 55.26%, 44.7% of the patients had a decrease in hsCRP, TNF-α and IL-6 respectively. Among responders hsCRP and TNF-α showed significant decrease in levels from the baseline (p <0.05). Modified SF-36 QOL questionnaire mean score revealed significant improvement in general health (p < 0.05). Among secondary parameters renal biomarkers like urea, BUN and sodium showed statistically significant decrease (p <0.05).Conclusions: This study establishes the safety and anti-inflammatory efficacy of this symbiotic supplement. To our knowledge this is the first study looking at anti-inflammatory role of symbiotic in CKD 5D Patients. A placebo controlled, double blinded study with a larger sample size is warranted in future to further establish these findings.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zuray Corredor ◽  
Miguel Inácio da Silva Filho ◽  
Lara Rodríguez-Ribera ◽  
Antonia Velázquez ◽  
Alba Hernández ◽  
...  

AbstractChronic kidney disease (CKD) patients have many affected physiological pathways. Variations in the genes regulating these pathways might affect the incidence and predisposition to this disease. A total of 722 Spanish adults, including 548 patients and 174 controls, were genotyped to better understand the effects of genetic risk loci on the susceptibility to CKD. We analyzed 38 single nucleotide polymorphisms (SNPs) in candidate genes associated with the inflammatory response (interleukins IL-1A, IL-4, IL-6, IL-10, TNF-α, ICAM-1), fibrogenesis (TGFB1), homocysteine synthesis (MTHFR), DNA repair (OGG1, MUTYH, XRCC1, ERCC2, ERCC4), renin-angiotensin-aldosterone system (CYP11B2, AGT), phase-II metabolism (GSTP1, GSTO1, GSTO2), antioxidant capacity (SOD1, SOD2, CAT, GPX1, GPX3, GPX4), and some other genes previously reported to be associated with CKD (GLO1, SLC7A9, SHROOM3, UMOD, VEGFA, MGP, KL). The results showed associations of GPX1, GSTO1, GSTO2, UMOD, and MGP with CKD. Additionally, associations with CKD related pathologies, such as hypertension (GPX4, CYP11B2, ERCC4), cardiovascular disease, diabetes and cancer predisposition (ERCC2) were also observed. Different genes showed association with biochemical parameters characteristic for CKD, such as creatinine (GPX1, GSTO1, GSTO2, KL, MGP), glomerular filtration rate (GPX1, GSTO1, KL, ICAM-1, MGP), hemoglobin (ERCC2, SHROOM3), resistance index erythropoietin (SOD2, VEGFA, MTHFR, KL), albumin (SOD1, GSTO2, ERCC2, SOD2), phosphorus (IL-4, ERCC4 SOD1, GPX4, GPX1), parathyroid hormone (IL-1A, IL-6, SHROOM3, UMOD, ICAM-1), C-reactive protein (SOD2, TGFB1,GSTP1, XRCC1), and ferritin (SOD2, GSTP1, SLC7A9, GPX4). To our knowledge, this is the second comprehensive study carried out in Spanish patients linking genetic polymorphisms and CKD.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5312-5312
Author(s):  
Lei Shen ◽  
Guoyuan Lu ◽  
Ningzheng Dong ◽  
Liqiong Jiang ◽  
Zhenni Ma ◽  
...  

Abstract Abstract 5312 Patients with chronic kidney disease (CKD) have increased risks of endothelial dysfunction and thrombosis. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. von Willebrand factor (VWF), a well-known index of endothelial damage, has been reported to increase both in CKD and inflammatory states. ADAMTS13 is a specific VWF-cleaving protease, and some reports suggested that the ratio of VWF and ADAMTS13 maybe more useful in the diagnosis and treatment evaluation of patients in the prothrombotic state. So we assessed the relationships among endothelial dysfunction, ADAMTS13 activity, and levels of inflammatory cytokines in CKD patients. CKD patients were classified into 3 groups: chronic glomerulonephritis group (CGN, n = 31), idiopathic nephritic syndrome group (NS, n = 32), and lupus nephritis group (LN, n = 41). We measured the plasma levels of TNF-α, VWF antigen (VWF:Ag), and ADAMTS13 activity by using an ELISA-based method in CKD patients (n = 104) and normal controls (n = 32). The ratio of the VWF:Ag level to ADAMTS13 activity was calculated. The VWF:Ag level was significantly higher and the ADAMTS13 activity was significantly lower in all the disease groups than in the controls (P < 0.01). ADAMTS13 activity was lower in the NS group than in the CGN and LN groups (P < 0.05) (Table 1). The TNF-α (pg/mL) level was higher in the CKD group than in the control group (CGN: 3.19 ± 1.01; NS: 3.26 ± 1.18; LN: 3.24 ± 1.24; Control: 2.27 ± 1.23; P < 0.01; P < 0.01). TNF-α was positively correlated with the VWF:Ag level (r = 0.242, P = 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r = −0.193, P = 0.049). ADAMTS13 activity was negatively correlated with the cholesterol level in CKD patients (r = −0.2, P = 0.042). TNF-α level in CKD was positively correlated with the VWF:Ag level and negatively correlated with GFR, which suggests that inflammation might be a major cause of endothelial dysfunction and an index for renal function. The VWF:Ag level increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state. Table 1. The plasma VWF:Ag level, ADAMTS13 activity, and the VWF/ADAMTS13 ratio in the CGN, NS, LN, and control groups N VWF (%) ADAMTS13 (%) VWF/ADAMTS13 CGN 31 198.25 ± 140.20** 61.93 ± 22.47**# 3.83 ± 3.29** NS 32 149.94 ± 74.50** 48.87 ± 18.63** 3.42 ± 1.59** LN 41 234.75 ± 134.91**## 67.81 ± 22.30**## 3.79 ± 2.52** CONTROL 32 99.55 ± 21.37 94.37 ± 23.66 1.12 ± 0.37 vs. CONTROL ** P < 0.01; vs. NS ## p < 0.01, # P < 0.05 Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 9 (B) ◽  
pp. 614-619
Author(s):  
Rudi Supriyadi ◽  
Nenny Agustanti ◽  
Marcella Adisuhanto

BACKGROUND: Hepatitis C infection could increase the morbidity and mortality of chronic kidney disease patients on hemodialysis by enhancing the inflammatory process. Tumor Necrosis Factor-alpha (TNF-a) is the main regulator of the inflammatory cascade, which could induce malnutrition and suppress cholesterol and albumin production in the liver. AIM: Therefore, this study aimed to determine the correlation between serum TNF-a level with serum albumin and cholesterol levels in chronic kidney disease patients on hemodialysis with and without hepatitis C infection. METHODS: This research was an analytical cross-sectional study. The sample of this study consisted of patients undergoing routine hemodialysis at Dr. Hasan Sadikin Hospital, Bandung, in February 2020. The sample selection was using a random sampling method and analyzed with the Spearman rank correlation test. RESULTS: One hundred nineteen patients were divided into two groups, with hepatitis C infection (n=53) and without hepatitis C infection (n=66). The median value of serum TNF-α _was higher in the hepatitis C infection group compared to the group without hepatitis c infection (31.86 pg/ml vs 11.71 pg/ml, p <0.001). There was a correlation between serum TNF-α _and cholesterol in the hepatitis C infection (r = -0.246; p = 0.039) and without hepatitis c infection group (r = -0.256; p = 0.022). After adjusting with the duration of hemodialysis, this association was found to be significant in patients without Hepatitis C infection (p = 0.02) and borderline significant in patients with Hepatitis C infection (p = 0.09). There was no correlation between TNF-α _with albumin in both hepatitis C infection group (r = 0.082; p = 0.281) and without hepatitis C infection (r = -0.168; p = 0.094). CONCLUSION: Serum TNF-α _negatively correlates with cholesterol levels in chronic kidney disease patients on hemodialysis with and without hepatitis C infection. However, there was no correlation between TNF-α _and albumin level in both groups.


2018 ◽  
Vol 22 (5) ◽  
pp. 25-30
Author(s):  
N. V. Agranovich ◽  
L. A. Pilipovich ◽  
L. V. Albotova

Currently, accumulated a large amount of data on the role of inflammation in the vascular endothelium damage during the development of the chronic forms of many diseases. THE AIM:  identification of endothelial dysfunction (ED) biomarkers as early  predictors of CKD development in patients with chronic lung  diseases. PATIENTS AND METHODS. 123 patients with COPD aged 55-79 years were examined, studied features of clinical and anthropometric parameters, data of the main biochemical systemic  inflammation markers and vascular endothelial dysfunction, their  significance in the development of chronic kidney disease (CKD).  RESULTS. For the first time CKD was diagnosed in 51.2% of patients  with COPD. In comorbid patients with COPD and related CKD noted  more severe course of disease. Also in these patients detected  significantly elevated endothelial dysfunction indices. CRP and  fibrinogen levels were higher in all patients with COPD and authentically correlated with disease severety. Direct correlation  between CRP and TNF-α levels was revealed. Noted that tumor  necrosis factor was higher in smoker patients with COPD. Markers of  kidneys endothelial dysfunction – homocysteine, IL-6, IL-8 – were  significantly higher in patients with decreased GFR. Also in these  patients were detected increased levels of serum creatinine and  urea. Creatinine clearance inversely correlated with homocysteine  plasma level. In all cases of fibrinogen increase in patients with  COPD. Homocysteine level was also increased, but in combination  with CKD it was significantly higher: respectively 19,8±7,51 and  39,8 ± 7,14 μmol/L, p<0,005. CONCLUSION. The received  information confirms the hypothesis about the relationship of ED  biomarkers homocysteine, TNF-α, IL-6, IL-8 with the development of chronic kidney disease in comorbid patients with COPD. 


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Evangelia Dounousi ◽  
Constantinos Tellis ◽  
Paraskevi Pavlakou ◽  
Anila Duni ◽  
Vasillios Liakopoulos ◽  
...  

Proprotein convertase subtilisin/kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress, and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress, and endothelial damage in patients with CKD. Patients and Methods. Ninety-two patients with CKD stages II-ΙV (eGFR CKD-EPI 47.3 ± 25.7  ml/min/1.73 m2, mean age 66 years, 51 men) were included in the study. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension, diabetes mellitus, and history of cardiovascular disease), renal function indices (eGFR, proteinuria–UPR/24 h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), APO-A1, and APO-B), and soluble biomarkers of inflammation, oxidative stress, and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, and sVCAM-1). Results. The mean plasma value of PCSK9 was 278.1 ng/ml. PCSK9 levels showed direct correlation with serum triglycerides ( p = 0.03 ), Lp(a) ( p = 0.01 ), and sICAM-1 levels ( p = 0.03 ). There was no significant correlation between PCSK9 levels and indices of the renal function, other lipid profile parameters, inflammatory markers, or comorbidities. Multiple regression analysis showed a significant effect of Lp(a) on PCSK9 levels, and for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935-5.228, p = 0.006 ). At the same time, patients receiving statins are expected to have on average 63.8 ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6-113.5, p = 0.012 ). Conclusion. Plasma levels of PCSK9 in nondialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD.


Author(s):  
Pēteris Tretjakovs ◽  
Antra Jurka ◽  
Inga Bormane ◽  
Indra Miķelsone ◽  
Dace Reihmane ◽  
...  

Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.


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