Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study (original) (raw)
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Current Cardiovascular Risk Reports, 2012
Generic chronic kidney disease (CKD) can be defined by a lowered estimated glomerular filtration rate (eGFR) and/or "kidney damage," the latter by abnormal albuminuria (>30 mg/d), imaging, urinalysis, or renal pathology, that persists for at least 3 months. According to current schema, any adult with an eGFR <60 mL/min/ 1.73 m 2 for 3 months or longer can be regarded as having CKD. This definition may be to all-encompassing and lead to over-diagnosis in some groups (particularly the elderly). It is currently undergoing a refinement. Although eGFR and albuminuria are principally used to define CKD and stratify its prognosis, a number of new biomarkers, such as NGAL, FGF-23, Cystatin C, uric acid, and ADMA are emerging that may have utility in enhancing the accuracy of predicting cardiovascular risk in CKD. As currently defined, CKD has important implications for the future risk of cardiovascular events. Albuminuria and lowered eGFR both contribute independently to the associations with cardiovascular risk. Albuminuria does so in a continuous log-linear manner whereas eGFR demonstrates a threshold effect (at around 45-60 mL/min/1.73 m 2). The precise mechanisms underlying these associations are complex and poorly understood, but enhanced atherogenesis, diffuse endothelial injury, and left ventricular hypertrophy are important factors. Left ventricular hypertrophy is a major risk factor for congestive heart failure and sudden cardiac death in advanced CKD and it may become a specific target for interventions in the future, especially as the role of elevation in serum FGF-23 levels in the genesis of left ventricular hypertrophy are better understood.
Current Issues in Pharmacy and Medical Sciences
This comes about because of a lack of predicted biomarkers in the risk analysis of CVD events in chronic kidney disease (CKD) patients. The present study aimed to determine the clinical utility of independent, predictable biomarkers such as serum creatinine, estimated Glomerular Filtration Rate (eGFR), high sensitive C-Reactive protein (hsCRP), fibrinogen and lipid profile as early predictors of CVD in CKD at stage III/IV. Methods. This is a case-control study that includes a sample size of 100 patients of cases and 100 patients of controls who were recruited from November 2020 to April 2021, from the Nephrology department of the Visakhapatnam tertiary care teaching hospital, and present with chronic kidney disease – stage III/IV. The subjects’ general conditions (age, gender, height, weight, systolic blood pressure, diastolic blood pressure, and smoking history); underlying diseases (coronary heart disease and diabetes mellitus) were recorded. Fasting venous blood samples were coll...
Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome
International Journal of Molecular Sciences
In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value. Due to the development of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, the introduction of novel techniques will allow for the identification of novel biomarkers in renal diseases. This review presents some new possible biomarkers in the diagnosis of CKD and in the prediction of outcome, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), uromodulin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic biomarkers. Complicated pathomechanisms of CKD development and progression require not a single marker but their combination in order to mirror all types of alterations occurring in the course of this disease. It seems that in the not so distant future, conventional markers may be exchanged for new ones, however, confirmation of their efficacy, sensitivity and specificity as well as the reduction of analysis costs are required.
Evaluating Cardiovascular Risk in Chronic Kidney Disease Patients: A Biomarker Approach
Sains Malaysiana, 2018
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to determine the roles of CVD biomarkers in CKD patients. This was a case-control study which recruited consecutive patients with stage 2-4 CKD patients with and without CVD. Serum levels of highly-sensitive C reactive protein (hs-CRP), cystatin C (CysC), asymmetrical dimetylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were measured. Sixty two stage 2-4 CKD patients with a mean age of 60.3 ± 10.4 years were recruited. Twenty three (37.1%) of them had CVD. Those CKD patients with CVD were older (64.1±8.0 vs 58.1± 1.1, p<0.05) and had significantly higher systolic blood pressure (139.4 ± 16.2 vs 129.4 ± 14.8 mmHg, p<0.05). Diabetic patients had 8 times (95% CI 1.25-51.77, p< 0.05) higher risk to develop CVD. CKD patients with CVD had a higher serum creatinine (185.0 ± 54.1 vs 154.1 ± 54.4 μmol/L, p<0.05), a lower estimated glomerular filtration rate (33.7 ± 12.2 vs 42.2 ± 14.5 mL/min/1.73m 2 p<0.05) and a lower triglyceride levels (1.3 (1.1-1.7) vs 1.8 (1.4-2.3) mmol/L, p<0.05), compared to those without CVD. Fasting blood sugar was 7.1 ± 2.7 mmol/L in CVD group and 6.3 ± 1.6 mmol/L in non CVD group (p>0.05). There were no differences in their mean serum levels of hs-CRP, CysC, ADMA and SDMA. Risk factors including age, diabetes mellitus, hypertension and renal functions were still the most important CVD risk factors in CKD patients.
Review article: Biomarkers of clinical outcomes in advanced chronic kidney disease
Nephrology, 2009
Chronic kidney disease (CKD) is a complex condition, where the decrease in kidney function is accompanied by numerous metabolic changes affecting virtually all the organ systems of the human body. Many of the biomarkers characteristic of the individually affected organ systems have been associated with adverse outcomes including higher mortality in advanced CKD, whereas in persons without CKD these biomarkers may have no bearing on survival. It is believed that the high mortality seen in CKD is a result of several abnormalities conspiring to induce or aggravate a heightened degree of cardiovascular morbidity and predisposition to wasting syndrome. Not all the biomarkers may, however, be causally responsible for the adverse outcomes associated with them. We review various biomarkers of protein-energy wasting, inflammation, oxidative stress, potassium disarrays, acid-base disorders, bone and mineral disorders, glycemic status, and anemia. Although all of these biomarkers have shown associations with worsened outcomes in CKD, markers of protein-energy wasting, especially serum albumin, remain the strongest predictor of survival in CKD patients, especially those undergoing maintenance dialysis treatment. We also review the putative pathophysiologic mechanisms behind these associations, and present potential therapeutic interventions that could result in remedies to improve poor clinical outcomes in CKD, pending the results of current and future controlled trials.
Markers of increased cardiovascular risk in patients with chronic kidney disease
Lipids in Health and Disease, 2014
Background Epidemiological studies have shown that chronic kidney disease (CKD) is an important risk factor for atherosclerosis and cardiovascular disease (CAD). The aim of the study was to determine markers of increased risk of CAD and to achieve a better understanding of agents implicated in the process of atherosclerosis in CKD patients. Methods The study group consisted of a total of 139 patients with CKD while the control group comprised 45 healthy volunteers. Concentrations of osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid (Gla) protein (MGP), fetuin A, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1) and renalase were measured by the ELISA method. Results We observed decreased levels of fetuin A (control vs. CKD group: 37.5 vs. 33.2 ng/ml, p = 0.018), and increased concentrations of osteocalcin (control vs. CKD group: 9.1 ± 6.0 vs. 13.6 ± 10.3 ng/ml, p = 0.05), MMP-2 (113.1 ± 75.0 vs. 166.0 ± 129.9 ng/ml, p = 0.045), TIMP-2 (22.1 ± 5.1 vs. 25.4 ± 7,0 ng/ml, p = 0.005) and renalase (251.0 ± 157 vs. 316.1 ± 155.3 ng/ml, p = 0.026). In patients with CKD (in comparison to control group), left ventricle ejection fraction: 53.0 ± 3,5% vs. 48.5%, p = 0.012) and calcification of the aortic valve (9.5% vs. 39.8%, p = 0.008) were observed more frequently. Conclusions Decreased levels of fetuin A and increased concentration of osteocalcin, renalase, MMP-2 and TIMP-2 suggest that these factors may be involved in the pathogenesis of CAD in patients with CKD. Significantly increased indices of cardiac hypertrophy and its dysfunction in patients with CKD are indicators of pathological mechanisms occurring in cardiovascular system in this group of patients.
Lipids in health and disease, 2016
The prevalence of chronic kidney disease is rising continuously. Cardiovascular disease is among leading causes of death and premature mortality of patients with chronic kidney disease. Even the earliest stages of chronic kidney disease are associated with higher risk of subsequent coronary heart disease. The aim of this study was to determine markers of increased risk of atherosclerosis in CKD. The study group consisted of a total of 80 patients (20 patients with stage I/II CKD, 20 with stage III CKD, 20 stage IV CKD and 20 stage V/dialysis) and 24 healthy volunteers. Levels of proteins (osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid protein, fetuin A, MMP-2, MMP-9, TIMP-1, TIMP-2) and biochemical parameters were measured to analyse their influence on atherosclerosis risk in CKD patients. Cardiac echocardiography was performed to assess structural integrity and function, presence of left ventricular hypertrophy and systolic and diastolic function dysfuncti...
Cardiovascular Biomarkers in Chronic Kidney Disease
Journal of Medical Biochemistry, 2010
Kratak sadr`aj: Kod pacijenata sa hroni~nim oboljenjem bubrega, kardiovaskularni morbiditet i mortalitet su zn a ~ajno povi{eni. Iako se ne mo`e smatrati ekvivalentom rizika za kar dio vaskularne bolesti, veruje se da je bubre`na insufici jencija nezavisni prediktor pove}anog kardiovasku lar nog rizika i da se taj rizik pove}ava sa slabljenjem bubre`ne funkcije. Ova udru`enost je veoma kompleksna i danas se {iroko koristi termin kardiorenalni sindrom. Kardiovaskularna bolest u hroni~noj bolesti bubrega obi~no se ispoljava kao ishemijska bolest srca (u obliku angine, akutnog koronarnog sindroma ili nagle sr~ane smrti), cerebrovaskularna bolest, periferna vaskularna bolest i kongestivna bolest srca. Vaskularna bolest obuhvata aterosklerozu i vaskularne kalcifikacije, dok kardio miopatija obuhvata hipertrofiju leve komore, kardijalnu fibrozu i sistolnu i dijastolnu disfunkciju leve komore. Pored dobro poznatih tradicionalnih faktora rizika kao {to su hipertenzija, dislipidemija, insulinska rezistencija i diabetes mellitus, u osnovi ove udru`enosti je i siner gi sti~ko delovanje netradicionalnih faktora rizika kao {to su pove}anje odnosa kalcijum-fosfor, hiperparatireoidizam, anemija, hemodinamsko optere}enje, pothranjenost, za pa ljenje, hiperhomocisteinemija, izmenjena sinteza azot-mo noksida i pove}an oksidativni stres. U radu se razma traju dosada{nja saznanja o zna~aju pojedinih ure mijskih toksi na, natriureti~kih peptida, biohemijskih marke ra poreme}aja u homeostazi kalcijuma i fosfora, sistem ske inflamacije, oksidativnog stresa i dislipidemije.
Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient
Clinical Journal of the American Society of Nephrology, 2008
Premature cardiovascular disease (CVD), including stroke, peripheral vascular disease, sudden death, coronary artery disease, and congestive heart failure, is a notorious problem in patients with chronic kidney disease (CKD). Because the presence of CVD is independently associated with kidney function decline, it appears that the relationship between CKD and CVD is reciprocal or bidirectional, and that it is this association that leads to the vicious circle contributing to premature death. As randomized, placebo-controlled trials have so far been disappointing and unable to show a survival benefit of various treatment strategies, such a lipid-lowering, increased dialysis dose and normalization of hemoglobin, the risk factor profile seems to be different in CKD compared with the general population. Indeed, seemingly paradoxical associations between traditional risk factors and cardiovascular outcome in patients with advanced CKD have complicated our efforts to identify the real cardiovascular culprits. This review focuses on the many new pieces that need to be fit into the complicated puzzle of uremic vascular disease, including persistent inflammation, endothelial dysfunction, oxidative stress, and vascular ossification. Each of these is not only highly prevalent in CKD but also more strongly linked to CVD in these patients than in the general population. However, a causal relationship between these new markers and CVD in CKD patients remains to be established. Finally, two novel disciplines, proteomics and epigenetics, will be discussed, because these tools may be helpful in the understanding of the discussed vascular risk factors.