scholarly journals MO440KLOTHO AS A BIOMARKER OF SUBCLINICAL CARDIOVASCULAR DISEASE IN CHRONIC KIDNEY DISEASE: A PROOF-OF-CONCEPT STUDY*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Carla Ferri ◽  
Javier Donate-Correa ◽  
Ernesto Martín-Núñez ◽  
Nayra Pérez-Delgado ◽  
Ainhoa González-Luis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Levels ◽  
Receiver Operating Curve ◽  
Atherosclerotic Cardiovascular Disease ◽  
Proof Of Concept ◽  
Expression Levels ◽  
Concept Study

Abstract Background and Aims Cardiovascular disease (CVD) is the major cause of mortality among chronic kidney disease (CKD) patients. Reductions in serum Klotho levels are related to the prevalence of CVD in CKD patients. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs), are associated with subclinical atherosclerotic cardiovascular disease (sCVD) in these subjects. In this proof-of-concept study, we analyzed in a group of CKD patients the relationship between Klotho and two markers of sCVD: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Method Gene expression in PBCs and serum levels of Klotho and inflammatory cytokines (TNF, IL6 and IL10) were measured in 103 CKD patients (stages 3-4), older than 18 years of age, and without known atherosclerotic cardiovascular disease. Biochemical data were obtained following standardized clinical methods. The presence of sCVD was defined as ABI < 0.9 and/or CIMT ≥ 0.9 mm. Patients with ABI values ≥ 1.3 were excluded. Results Patients with sCVD presented lower serum and PBCs expression levels of Klotho (P<0.001 for both). Stratified analysis showed that upper tertiles of both serum and PBCs expression levels of Klotho presented significantly higher ABI (P<0.001 for both Klotho determinations) and lower CIMT (P<0.001 for serum levels and P<0.01 for KL expression in PBCs), which resulted in a lower prevalence of sCVD (P<0.001 for both determinations of Klotho). Correlation analysis showed that both serum and PBCs mRNA Klotho levels were positively correlated with ABI (r=0.556, P<0.0001; and r=0.373, P<0.0001, respectively) and inversely correlated with CIMT (r=-0.541, P<0.0001; and r=-0.437, P<0.0001, respectively). Among inflammatory markers, only serum IL6 levels presented significant associations with sCVD, being inversely related with ABI (r=-0.568, P<0.0001) and positively associated with CIMT (r=0.558, P<0.0001). Multiple regression analysis with ABI and CIMT as dependent variables demonstrated that both Klotho variables, together with serum IL6, were positively and significantly associated with ABI (adjusted R2=0.511, P<0,0001) and CIMT (adjusted R2=0.445, P<0,0001) values, independently of traditional and emergent cardiovascular risk factors. Multivariate logistic regression, using the presence/absence of sCVD as the dependent variable, showed that circulating Klotho, and its expression in PBCs constituted independent protective factors for sCVD [OR (95% CI): 0.993 (P=0.002) and 0.231 (P=0.025), respectively]. Receiver operating curve (ROC) analysis pointed to the prognostic ability for sCVD of serum Klotho (area under the curve [AUC]: 0.817, 95% CI: 0.736–0.898, P<0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: 0.647–0.836, P<0.001). Conclusion The reductions in serum soluble and PBCs expression levels of Klotho in CKD patients are independently associated with the presence of sCVD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could reduce the impact of CVD in CKD patients is warranted.

KLOTHO as a biomarker of subclinical cardiovascular disease in chronic kidney disease: A proof-of-concept study

2021 ◽  
Vol 331 ◽  
pp. e237
Author(s):  
C.M. Ferri ◽  
J.J. Donate-Correa ◽  
E. Martín-Núñez ◽  
N. Pérez-Delgado ◽  
A. González-Luis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Proof Of Concept ◽  
Concept Study ◽  
Subclinical Cardiovascular Disease

scholarly journals Low statin use in nondialysis-dependent chronic kidney disease in the absence of clinical atherosclerotic cardiovascular disease or diabetes

2019 ◽  
Vol 12 (4) ◽  
pp. 530-537
Author(s):  
Talar W Markossian ◽  
Holly J Kramer ◽  
Nicholas J Burge ◽  
Ivan V Pacold ◽  
David J Leehey ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Risk Equation ◽  
Diabetes Status ◽  
Increased Risk ◽  
Ascvd Risk ◽  
Risk Equivalent ◽  
Statin Use

Abstract Background Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD. Unless physicians recognize the heightened ASCVD risk in this population, statins may not be prescribed in the absence of clinical cardiovascular disease or diabetes, a recognized ASCVD risk equivalent. We examined statin use in adults with nondialysis-dependent CKD and examined whether the use differed in the presence of clinical ASCVD and diabetes. Methods This study ascertained statin use from pharmacy dispensing records during fiscal years 2012 and 2013 from the US Department of Veterans Affairs Healthcare System. The study included 581 344 veterans aged ≥50 years with nondialysis-dependent CKD Stages 3–5 with no history of kidney transplantation or dialysis. The 10-year predicted ASCVD risk was calculated with the pooled risk equation. Results Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P < 0.001). The 10-year predicted ASCVD risk was ≥7.5% in 95.1% of veterans with CKD, regardless of diabetes status. Conclusions Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.

scholarly journals Epigenetics: Pharmacology and Modification Mechanisms Involved in Cardiac, Hepatic and Renal Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 260-266
Author(s):  
Sagar. S. Waghmare ◽  
O.G. Bhusnure ◽  
M. R. Mali ◽  
S.T. Mule
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Epigenetic Modification ◽  
Hepatic Disease ◽  
Human Diseases ◽  
Future Perspective ◽  
The Past

For a long time scientists have tried to describe disorders are due to genetic as well as environmental factors. In the past few years, revolution in technology that has made it possible to decipher the human genome. Epigenetics explains the capability gene expression regulation without modifying the genetic sequence. Epigenetic mechanisms are rooted changes in molecules, or nuclear characteristics that can alter gene expression without altering the sequences of DNA, i.e. DNA methylation, histone modification, and non-coding RNAs. Learning of the fundamental epigenetic modification allowing gene expression as well as cellular phenotype are advanced that novel insights into the epigenetic control of cardiovascular disease, hepatic disease, as well as chronic kidney disease are now emerging. From a half of century ago, in human disease the role of epigenetics has been considered. This subject has attracted many interests in the past decade, especially in complicated diseases like cardiovascular disease, hepatic disease as well as chronic kidney disease. This review first illustrates the history and classification of epigenetic modifications and the factors (i.e. genetic, environment, dietary, thought process and lifestyle) affecting to the epigenetics mechanisms. Likewise, the epigenetics role in human diseases is think out by targeting on some diseases and at the end, we have given the future perspective of this field. This review article provides concepts with some examples to describe a broad view of distinct aspects of epigenetics in biology and human diseases. Keywords: - Epigenetics, DNA methylation, Histone modifications, microRNAs and Gene expression and Disease.

scholarly journals Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease–The Possible Role of an Abnormal Serum Fatty Acid Profile

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 98
Author(s):  
Justyna Korczyńska ◽  
Aleksandra Czumaj ◽  
Michał Chmielewski ◽  
Maciej Śledziński ◽  
Adriana Mika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mrna Levels ◽  
Serum Fatty Acid ◽  
Serum Leptin

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC–MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.

scholarly journals Association between Serum Neopterin and Inflammatory Activation in Chronic Kidney Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ashok Kumar Yadav ◽  
Vinod Sharma ◽  
Vivekanand Jha
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Cell Mediated Immunity ◽  
Serum Neopterin ◽  
Markers Of Inflammation ◽  
Stage 4 ◽  
Highly Sensitive

Background.The serum levels of neopterin, a marker associated with cell-mediated immunity are elevated in chronic kidney disease (CKD). We evaluated serum neopterin levels and investigated its association with markers of inflammation in a cross-section of CKD subjects without known cardiovascular disease.Methods.Serum neopterin levels were measured in 118 patients with stage 3–5 CKD and 41 healthy subjects with normal kidney function (HC). Patients with known cardiovascular disease were excluded. We also estimated highly sensitive CRP (hsCRP) and interluekin-6 (IL-6), tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ) in the CKD subjects. All assays were done using commercially available ELISA kits. The correlation between neopterin and markers of inflammation were investigated.Results.Of the CKD population, 82 were in stage 5 (60 stage 5 D), 24 in stage 4, and 12 in stage 3. The mean age was51.04±1.3years and 66% were males. The commonest cause of CKD was diabetes (36%). Serum neopterin levels were 5-fold higher in CKD patients as compared to HC (74.8±3.6versus15.0±2.8 nmol/L,P<0.0001). There was a graded increase of serum neopterin from stages 3 to 4 and 5. CKD 5 D patients exhibited significantly higher levels compared to nondialysis stage 5 patients (P<0.0001). An inverse correlation was noted between serum neopterin and eGFR (r=−0.359,P<0.0001). Serum neopterin correlated with hsCRP (r=0.285,P=0.002), IL-6 (r=0.212,P=0.034), and IFN-γ(r=0.32,P=0.001) but not with TNF-α.Conclusion.Serum neopterin level is elevated and correlates with the severity of CKD. The elevation correlates with elevation of most, but not all, inflammatory markers. Its role in future development of cardiovascular disease and modulation with anti-inflammatory therapies needs further studies.

Elevated serum levels of S-adenosylhomocysteine, but not homocysteine, are associated with cardiovascular disease in stage 5 chronic kidney disease patients

2008 ◽  
Vol 395 (1-2) ◽  
pp. 106-110 ◽  
Author(s):  
Alessandro Valli ◽  
Juan J. Carrero ◽  
Abdul Rashid Qureshi ◽  
Giacomo Garibotto ◽  
Peter Bárány ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elevated Serum ◽  
Serum Levels
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