The Impact of Selected Factors on the Cardiovascular System in Chronic Kidney Disease

Completed

• Conditions: Inflammation; Chronic Kidney Diseases; Cardiovascular Diseases; Atherosclerosis of Artery; Dialysis; Complications

• Registration Number: NCT05214872
• Lead Sponsor: Poznan University of Medical Sciences

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.

Study Timeline

• Study Start: 2016-03-25
• Primary Completion: 2020-09-10
• Study Completion: 2020-09-30
• Study First Submitted: 2021-12-09
• Status Verified: 2022-01
• Study First Submitted QC: 2022-01-25
• Last Update Submitted: 2022-01-25
• Study First Posted: 2022-01-31
• Last Update Posted: 2022-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Diagnostic test: parameters of iron metabolism - total iron-binding capacity (TIBC)	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)	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)	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]	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)	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)	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	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)	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)	3 years	platelet count (PLT) \[10\^9/l\] was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA).
Diagnostic test: urea	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	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).	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	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)	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	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)	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)	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)	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)	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)	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)	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	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	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)	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	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: parameters of iron metabolism - the unsaturated iron-binding capacity (UIBC)	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	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)	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)	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)	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)	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	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]	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]	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)	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)	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	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)	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)	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)	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.
Device: vessel stiffness assessments - reflection index (RI)	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)	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)	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)	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.
Diagnostic test: selected parameters of oxidative stress - myeloperoxidase (MPO)	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)	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	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)	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)	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	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]	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) \[mm Hg\]
Diagnostic test: liver enzymes activity assessment - aspartate transaminase (AST)	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)	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.
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)	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 \[bpm\]
The MMP-9/TIMP-1 ratio assessment	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.

Trial Locations

Locations (1)

Poznan University of Medical Sciences; 🇵🇱 Poznań, Poland