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Clinical Trials/NCT05214872
NCT05214872
Completed
Not Applicable

Assessment of the Impact of Selected Factors on the Cardiovascular System in Patients With Different Chronic Kidney Disease Stages

Poznan University of Medical Sciences1 site in 1 country252 target enrollmentMarch 25, 2016

Overview

Phase
Not Applicable
Intervention
Not specified
Conditions
Atherosclerosis of Artery
Sponsor
Poznan University of Medical Sciences
Enrollment
252
Locations
1
Primary Endpoint
Diagnostic test: parameters of iron metabolism - total iron-binding capacity (TIBC)
Status
Completed
Last Updated
4 years ago

Overview

Brief Summary

Chronic kidney disease (CKD), is characterized by accelerated development of atherosclerosis and advanced remodelling of vessels and the heart. It is associated with many factors, including inflammation, arterial hypertension, hyperlipidemia, hyperhomocysteinemia, secondary hyperparathyroidism, and oxidative stress. Hypertension is one of the most critical risk factors for cardiovascular complications. It leads to the formation of structural changes in the vascular system: it impairs the activity of the endothelium, causes hypertrophy and remodelling of the vascular wall, reduces the susceptibility of the vessels and accelerates the development of atherosclerosis. This study aimed to identify the processes and their representative markers, the concentration of which in the serum may reflect the cardiovascular system status and can predict the increased mortality in HD patients.

Detailed Description

Chronic Kidney Disease has a significant impact on the cardiovascular system. From many different complications of CKD, one to mention is arterial stiffness. This disorder results from many pathologies, including inflammation, arterial hypertension, carbohydrate metabolic disorders, lipid disorders, vascular calcification, chronic inflammation, and oxidative stress. The main goal of this study was to analyze the mechanisms leading to the increased tendency to cardiovascular disturbances in CKD, with particular focus on the parameters of oxidative stress, inflammation and the results of imaging examinations (intima-media thickness (IMT) assessments) and other non-invasive cardiological examinations based on the results using the Portapres device (Finapres Medical Systems (FMS), the Netherlands), the SphygmoCor tonometer (AtCor Medical), the Colin blood pressure monitor (BMP)-7000 (Japan) Pulse Trace 2000 (Micro Medical Ltd., Rochester, Kent, United Kingdom) The Accuson CV 70 system (Siemens) with a 10 megahertz (Mhz) transducer. Besides, studied participants were followed 2 years after enrollment to study for recording cardiovascular-related death.

Registry
clinicaltrials.gov
Start Date
March 25, 2016
End Date
September 30, 2020
Last Updated
4 years ago
Study Type
Observational
Sex
All

Investigators

Sponsor
Poznan University of Medical Sciences
Responsible Party
Principal Investigator
Principal Investigator

Dorota Formanowicz

MD.Ph.D. Associate Professor

Poznan University of Medical Sciences

Eligibility Criteria

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Outcomes

Primary Outcomes

Diagnostic test: parameters of iron metabolism - total iron-binding capacity (TIBC)

Time Frame: 3 years

total iron-binding capacity (TIBC) \[mg/dl\] - was determined with the Cobas Integra 400 plus biochemical analyzer from Roche Diagnostics, USA.

Diagnostic test: basic biochemical parameters: complete blood count - hemoglobin (HGB)

Time Frame: 3 years

hemoglobin (HGB) \[g/dl\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).

Diagnostic test: basic biochemical parameters: complete blood count - white blood cell count (WBC)

Time Frame: 3 years

white blood cells (WBC) \[10\^9/l\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).

Diagnostic test: liver enzymes activity assessment - alkaline phosphatase (ALP) [U/l]

Time Frame: 3 years

activity of alkaline phosphatase (ALP) \[U/l\] was assessed in the serum by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: intact parathormone (iPTH)

Time Frame: 3 years

intact parathormone (iPTH) \[mg/dl\] serum concentration was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic Test: selected inflammatory markers - interleukin 18 (IL-18)

Time Frame: 3 years

interleukin 18 (IL-18) \[pg/ml\] concentration in the serum was determined by Colorimetric Sandwich ELISA, Quantikine Human IL-18 R\&D Inc., USA.

Device: vessel stiffness assessments - peripheral pulse pressure/central pulse pressure (pPP/cPP) ratio

Time Frame: 3 years

Peripheral pulse pressure/central pulse pressure (pPP/cPP) ratio was assessed by dividing peripheral pulse pressure (pPP) \[mm Hg\] by central pulse pressure (cPP) \[mm Hg\].

Diagnostic test: basic biochemical parameters: complete blood count - hematocrit (HCT)

Time Frame: 3 years

hematocrit (HCT) \[l/l\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).

Diagnostic test: basic biochemical parameters: complete blood count - platelet count (PLT)

Time Frame: 3 years

platelet count (PLT) \[10\^9/l\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).

Diagnostic test: urea

Time Frame: 3 years

urea \[mg/dl\] concentration in the serum was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Estimated glomerular filtration rate (eGFR) [ml/min/1.73m^2] calculation

Time Frame: 3 years

eGFR - according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommendations was calculated based on the Modification of Diet in Renal Disease (MDRD) formula: eGFR = 186 x \[creatinine concentration in mg/dl\] - 1.154 x \[age in years\] - 0.203 x \[0.724\] for the female gender.

Diagnostic test: parameters of lipids metabolism in the serum low-density lipoprotein cholesterol (LDL-C).

Time Frame: 3 years

low-density lipoprotein (LDL-C) cholesterol concentration in the serum was determined from Friedewals' equation (LDL-C \[mg/dl\] = total cholesterol (T-C) \[mg/dl\] - HDL-C \[mg/dl\] - TG\[mg/dl\]/5). It was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: parameters of iron metabolism - iron

Time Frame: 3 years

iron concentration \[mg/dl\] in the serum - was assessed with the Cobas Integra 400 plus biochemical analyzer from Roche Diagnostics, USA;

Diagnostic test: basic biochemical parameters: complete blood count - red blood cell count (RBC)

Time Frame: 3 years

red blood cell count (RBC) \[10\^12/l\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).

Body mass index (BMI) [kg/m^2] calculation

Time Frame: 3 years

Body mass index (BMI) - \[kg/m\^2\] was calculated by dividing a person's weight (post-HD weight in HD group) \[kg\] by the squared their body height \[m\].

Diagnostic test: parameters of lipids metabolism in the serum - triglycerides (TG)

Time Frame: 3 years

triglycerides (TG) \[mg/dl\] concentration in the serum was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: glucose (Glu)

Time Frame: 3 years

glucose (Glu) \[mg/dl\] concentration in the serum was assessed by the routine technique using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: parameters of lipids metabolism in the serum - total cholesterol (T-C)

Time Frame: 3 years

total cholesterol (T-C) \[mg/dl\] concentration in the serum was assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: parameters of lipids metabolism in the serum - high-density lipoprotein cholesterol (HDL-C)

Time Frame: 3 years

high-density lipoprotein cholesterol (HDL-C) \[mg/dl\] concentration in the serum was assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: total protein (TP)

Time Frame: 3 years

total protein (TP) \[g/dl\] concentration in the serum was assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: albumin(ALB)

Time Frame: 3 years

albumin (ALB) \[g/dl\] concentration in the serum was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: parameters of iron metabolism - ferritin

Time Frame: 3 years

ferritin \[ng/ml\] concentration in the serum was determined with the Modular E-170 biochemical analyzer from Roche Diagnostics, USA.

Diagnostic test: total and ionized calcium

Time Frame: 3 years

total and ionized calcium \[mg/dl\] serum concentrations were assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: fibroblast growth factor 23 (FGF-23)

Time Frame: 3 years

fibroblast growth factor 23 (FGF-23) \[pg/ml\] serum concentration was analyzed using Human FGF-23 ELISA Kit, Sigma-Aldrich, USA.

Diagnostic test: creatinine

Time Frame: 3 years

creatinine \[mg/dl\] concentration in the serum was assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA (based on Jaffes' colorimetric method - the assay is based on the reaction of creatinine with sodium picrate as described by Jaffe).

Diagnostic test: liver enzymes activity assessment - aspartate transaminase (AST)

Time Frame: 3 years

activity of aspartate transaminase (AST) \[U/l\]; was assessed in the serum by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: liver enzymes activity assessment - alanine transaminase (ALT)

Time Frame: 3 years

activity of alanine transaminase (ALT) \[U/l\] was assessed in the serum by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: parameters of iron metabolism - the unsaturated iron-binding capacity (UIBC)

Time Frame: 3 years

unsaturated iron-binding capacity (UIBC) \[mg/dl\] was determined by an equation in which iron \[mg/dl\] concentration in plasma is subtracted from TIBC \[mg/dl\].

Diagnostic test: selected electrolytes assessment in the serum: magnesium

Time Frame: 3 years

magnesium (Mg) \[mg/dl\] serum concentration was assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: metalloproteinases - tissue inhibitor of metalloproteinase 1 (TIMP-1)

Time Frame: 3 years

tissue inhibitor of metalloproteinase 1 (TIMP-1) \[ng/ml\] concentration in the serum - was determined by the ELISA method using the Quantikine Human TIMP-1 kit, manufactured by R\&D Systems, Canada.

Diagnostic test: N-terminal pro-B-type natriuretic peptide (NT-proBNP)

Time Frame: 3 years

N-terminal pro-B-type natriuretic peptide (NT-proBNP) \[fmol/ml\] concentration in the serum was analyzed by enzyme immunoassay using the Nt-proBNP kit from Biomedica, Slovakia.

Diagnostic test: klotho (KL)

Time Frame: 3 years

klotho (KL) \[ng/ml\] serum concentration was analyzed by Human KL(Klotho) \[ng/ml\] ELISA Kit, Shanghai Sunred Biological Technology Co kit, China.

Diagnostic test: selected inflammatory markers - high-sensivity C-reactive protein (hsCRP)

Time Frame: 3 years

high-sensitivity C-reactive protein (hsCRP) \[mg/l\] concentration in the serum was measured using DADE Behring, USA, and the DADE nephelometer Behring Analyzer II.

Diagnostic test: selected inflammatory markers - neopterin

Time Frame: 3 years

neopterin \[nmol/l\] serum concentration was determined by using the Neopterin ELISA kit, DRG International, Inc., USA.

Diagnostic test: selected parameters of oxidative stress - carboxyethyle(lysine) (CEL) [µg/mg protein]

Time Frame: 3 years

carboxyethyle(lysine) (CEL) \[µg/mg protein\] concentration in the serum was assessed by competitive enzyme immunoassay (competitive ELISA) using CEL kits from Cell Biolabs Inc, USA.

Diagnostic test: selected parameters of oxidative stress - carbamyl protein groups [µg/mg protein]

Time Frame: 3 years

carbamyl protein groups \[µg/mg protein\] concentration in the serum were assessed by competitive enzyme immunoassay (competitive ELISA) using carbamyl protein groups kits from Cell Biolabs Inc, USA.

Diagnostic test: selected parameters of oxidative stress - soluble receptor for advanced glycation end products (sRAGE)

Time Frame: 3 years

soluble receptor for advanced glycation end products (sRAGE) \[µg/mg protein\] concentration in the serum was tested with enzymatic immunoassay (Quantikine ELISA) using R\&D Systems sRAGE kit, Canada.

Device: vessel stiffness assessments - vascular stiffness index (SI)

Time Frame: 3 years

The following parameter of vessel stiffness was assessed by Pulse Trace 2000 (Micro Medical Ltd., Rochester, Kent, United Kingdom): -vascular stiffness index (SI) \[m/s\].

Diagnostic test: phosphate

Time Frame: 3 years

phosphate \[mg/dl\] serum concentration was assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: selected electrolytes assessment in the serum: potassium (K) and sodium (Na)

Time Frame: 3 years

Electrolytes: potassium (K) \[mmol/l\] and sodium (Na) \[mmol/l\] serum concentrations were assessed by the routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

Diagnostic test: selected parameters of oxidative stress - 3-nitrotyrosine (3-NT)

Time Frame: 3 years

Serum concentration of 3-nitrotyrosine (3-NT) \[µmol/mg protein\] was determined with the enzyme immunoassay method (ELISA) for 3NT using Shanghai Sunred Biological Technology Co kits, China.

Diagnostic test: selected parameters of oxidative stress - carboxymethyle(lysine) (CML)

Time Frame: 3 years

Serum concentration of carboxymethyle(lysine) (CML) \[µg/mg protein\] was determined with the enzyme immunoassay method (ELISA) for CML using Shanghai Sunred Biological Technology Co kits, China.

Non-invasive cardiological examinations (2) with the use of Portapres device (Finapres Medical Systems (FMS), the Netherlands), the SphygmoCor tonometer (AtCor Medical), the Colin blood pressure monitor (BMP)-7000 (Japan) - heart rate (HR)

Time Frame: 3 years

Blood pressure was measured using the Colin BPM 7000 on both arms (participants were seated). Next, a piezoelectric tonometer Colin BPM was placed over the radial artery for the acquisition of the radial arterial pressure waveform in a supine position. This signal was sent to the SphygmoCor and after averaging various parameters have been assessed and recorded: - heart rate (HR) in beats per minute \[bpm\]

Device: vessel stiffness assessments - reflection index (RI)

Time Frame: 3 years

The following parameter of vessel stiffness was assessed by Pulse Trace 2000 (Micro Medical Ltd., Rochester, Kent, United Kingdom): - reflection index (RI) in percentages \[%\].

Diagnostic test: selected parameters of oxidative stress - advanced glycation ends products (AGE)

Time Frame: 3 years

Serum concentration of advanced glycation ends products (AGE) \[µg/mg protein\] was determined with the enzyme immunoassay method (ELISA) for AGE using Shanghai Sunred Biological Technology Co kits, China.

Diagnostic test: selected parameters of oxidative stress - advanced oxidation protein products (AOPP)

Time Frame: 3 years

Serum concentration of advanced oxidation protein products (AOPP) \[µmol/mg protein\] was determined with the enzyme immunoassay method (ELISA) for AOPP using Shanghai Sunred Biological Technology Co kits, China.

Diagnostic test: metalloproteinases - metalloproteinase 9 (MMP-9)

Time Frame: 3 years

metalloproteinase 9 (MMP-9) \[ng/ml\] concentration in the serum was determined by the ELISA method using the Quantikine Human MMP-9 (total) kit, by R\&D Systems, Canada.

The MMP-9/TIMP-1 ratio assessment

Time Frame: 3 years

the MMP-9/TIMP-1 ratio was calculated by the quotient of the MMP-9 \[ng/ml\] and the TIMP-1 \[ng/ml\] concentration.

Diagnostic test: selected parameters of oxidative stress - myeloperoxidase (MPO)

Time Frame: 3 years

myeloperoxidase (MPO) \[ng/ml\] in the serum - was determined by the ELISA method using the Quantikine Human MPO test by R\&D Systems kit, Canada.

Diagnostic test: selected parameters of oxidative stress - methylglyoxal (MG)

Time Frame: 3 years

methylglyoxal (MG) \[µg/mg protein\] concentration in the serum was assessed by competitive enzyme immunoassay (competitive ELISA) using MG kits from Cell Biolabs Inc, USA.

Non-invasive cardiological examinations (1) with the use of Portapres device (Finapres Medical Systems (FMS), the Netherlands), the SphygmoCor tonometer (AtCor Medical), the Colin blood pressure monitor (BMP)-7000 (Japan) - blood pressures

Time Frame: 3 years

Blood pressure was measured using the Colin BPM 7000 on both arms (participants were seated). Next, a piezoelectric tonometer Colin BPM was placed over the radial artery for the acquisition of the radial arterial pressure waveform in a supine position. This signal was sent to the SphygmoCor and after averaging various parameters have been assessed and recorded: * peripheral systolic blood pressure (sSBP) \[mmHg\]; * peripheral diastolic blood pressure (pDBP)\[mm Hg\]; * peripheral mean arterial pressure (pMAP) \[mm Hg\]; * peripheral end-systolic pressure (pESP) \[mm Hg\]; * central systolic blood pressure (cSBP) \[mm Hg\]; * central diastolic blood pressure (cDBP) \[mm Hg\]; * central mean arterial pressure (cMAP) \[mm Hg\]; * entral augmented pressure (cAP) \[mm Hg\]; * central mean pressure of diastole (cMPD) \[mm Hg\]; * central mean pressure of systole (cMPS)\[mm Hg\]; * central end-systolic pressure (cESP)\[mm Hg\]

Non-invasive cardiological examinations (3) with the use of Portapres device (Finapres Medical Systems (FMS), the Netherlands), the SphygmoCor tonometer (AtCor Medical), the Colin blood pressure monitor (BMP)-7000 (Japan) - ejection duration (ED)

Time Frame: 3 years

Blood pressure was measured using the Colin BPM 7000 on both arms (participants were seated). Next, a piezoelectric tonometer Colin BPM was placed over the radial artery for the acquisition of the radial arterial pressure waveform in a supine position. This signal was sent to the SphygmoCor and after averaging various parameters have been assessed and recorded: - ejection duration (ED) in milliseconds \[msec\]

Device: carotid intima-media thickness (IMT)

Time Frame: 3 years

Carotid intima-media thickness (IMT) \[mm\] was measured by The Accuson CV 70 system (Siemens) with a 10 megahertz (Mhz) transducer. Two longitudinal projections were assessed (anterolateral and posterolateral). The distal 1 cm of the common carotid artery just proximal to the bulb was measured by means of a computer analysis system (Medical Imaging Applications, LLC).

Cardiovascular (CV)-related death recording during 2-year follow-up

Time Frame: 2 years for each person qualified for the study

During a 2-year follow-up from the enrollment to this study, CV-related fatal incidents history has been recorded for each subject separately. The primary endpoint was fatal acute myocardial infarction (AMI) or acute ischemic stroke or any unexpected or sudden death only if autopsy proved CV-related. If there was doubt about the cause of death or there was no contact with the patient during the two years from study enrollment, that patient was excluded and not considered further.

Device: vessel stiffness assessments - peripheral (pPP) and central pulse pressure (cPP) [mm Hg]

Time Frame: 3 years

The following parameters of vessel stiffness were assessed by Pulse Trace 2000 (Micro Medical Ltd., Rochester, Kent, United Kingdom): * peripheral pulse pressure (pPP) \[mm Hg\]; * central pulse pressure (cPP) \[mm Hg\]

Study Sites (1)

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