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

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.

Conditions

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

Interventions

DIAGNOSTIC_TEST

laboratory parameters - complete blood count

the complete blood count was analyzed using Sysmex K-4500 Automated Hematology Analyzer (by GMI Inc., USA): * hemoglobin (HGB) \[g/dl\]; * red blood count (RBC) \[10\^12/l\]; * hematocrit (HCT) \[l/l\]; * white blood cells (WBC) \[10\^9/l\]; * platelet count (PLT) \[10\^9/l\]

OTHER

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

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

selected parameters of oxidative stress (1)

Serum concentration of: * advanced glycation ends products (AGE) \[µg/mg protein\]; * 3-nitrotyrosine (3-NT) \[µmol/mg protein\]; * advanced oxidation protein products (AOPP) \[µmol/mg protein\]; * carboxymethyle(lysine) (CML) \[µg/mg protein\] were determined with the enzyme immunoassay methods (ELISA) using Shanghai Sunred Biological Technology Co kits, China.

DIAGNOSTIC_TEST

metalloproteinases

metalloproteinases in the serum \[ng/ml\]: * metalloproteinase 9 (MMP-9) in the serum was determined by the ELISA method using the Quantikine Human MMP-9 (total) kit, by R\&D Systems, Canada; * tissue inhibitor of metalloproteinase 1 (TIMP-1) in the serum - was determined by the ELISA method using the Quantikine Human TIMP-1 kit, manufactured by R\&D Systems, Canada; * the MMP-9/TIMP-1 ratio was calculated by the quotient of the MMP-9 and the TIMP-1 concentration.

DIAGNOSTIC_TEST

parameters of lipids metabolism in the serum

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

DIAGNOSTIC_TEST

parameters of iron metabolism

* iron concentration \[mg/dl\] - was analyzed with the Cobas Integra 400 plus biochemical analyzer from Roche Diagnostics, USA; * total iron-binding capacity (TIBC) \[mg/dl\] - was analyzed with the Cobas Integra 400 plus biochemical analyzer from Roche Diagnostics, USA; * the unsaturated iron-binding capacity (UIBC) \[mg/dl\] was determined by an equation in which iron concentration in plasma is subtracted from TIBC \[mg/dl\]; * ferritin \[ng/ml\] concentration was determined with the Modular E-170 biochemical analyzer from Roche Diagnostics, USA.

DIAGNOSTIC_TEST

selected inflammatory markers

* high-sensitivity C-reactive protein (hsCRP) \[mg/l\] was measured using DADE Behring, USA and the DADE nephelometer Behring Analyzer II; * neopterin \[nmol/l\] was determined by using the Neopterin ELISA kit, DRG International, Inc., USA; * interleukin 18 (IL-18) \[pg/ml\] concentration was determined by Colorimetric Sandwich ELISA, Quantikine Human IL-18 R\&D Inc., USA.

DEVICE

carotid intima-media thickness (IMT)

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).

DEVICE

non-invasive cardiological examinations

For non-invasive cardiological examinations, the Portapres device (Finapres Medical Systems (FMS), the Netherlands), the SphygmoCor tonometer (AtCor Medical), the Colin blood pressure monitor (BMP)-7000 (Japan) were used. Main assessed variables: heart rate (HR) \[beats per minute \[bpm\]\]; ejection duration (ED) \[millisecons\]; peripheral systolic (pSBP) and diastolic blood pressure (pDBP) \[mm Hg\]; peripheral mean arterial pressure (pMAP) \[mm Hg\]; peripheral end-systolic pressure (pESP) \[mm Hg\]; central systolic (cSBP) and diastolic blood pressure (cDBP) \[mm Hg\]; central mean arterial pressure (cMAP) \[mm Hg\]; central augmented pressure (cAP) \[mmHg\]; central mean pressure of diastole (cMPD)\[mm Hg\]; central mean pressure of systole (cMPS) \[mm Hg\]; central end-systolic pressure (cESP) \[mm Hg\].

DEVICE

vessel stiffness assessment

The following parameters of vessel stiffness were assessed by Pulse Trace 2000 (Micro Medical Ltd., Rochester, Kent, United Kingdom): * reflection index (RI) \[in percentages \[%\]\]; * vascular stiffness index (SI) \[m/s\]; * peripheral pulse pressure (pPP) \[mm Hg\]; * central puls pressure (cPP) \[mm Hg\] * peripheral pulse pressure/central pulse pressure (pPP/cPP ratio).

OTHER

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

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.

DIAGNOSTIC_TEST

glucose (Glu)

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

DIAGNOSTIC_TEST

klotho

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

DIAGNOSTIC_TEST

fibroblast growth factor 23 (FGF-23)

FGF-23 \[pg/ml\] - was analyzed in rhe serum using Human FGF-23 ELISA Kit, Sigma-Aldrich, USA.

DIAGNOSTIC_TEST

parameters of calcium and phosphate metabolism

* total and ionized calcium \[mg/dl\], * phosphate \[mg/dl\], * intact parathormone (iPTH) \[mg/dl\] were assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

DIAGNOSTIC_TEST

liver enzymes activity assessment

activity of: * alanine transaminase (ALT) \[U/l\]; * aspartate transaminase (AST) \[U/l\]; * alkaline phosphatase (ALP) \[U/l\] were assessed by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

DIAGNOSTIC_TEST

total protein and albumin

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

DIAGNOSTIC_TEST

creatinine and urea

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

DIAGNOSTIC_TEST

selected parameters of oxidative stress (2)

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 (3) sRAGE

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

DIAGNOSTIC_TEST

selected parameters of oxidative stress (4) MG, CEL, carbamyl protein groups

* methylglyoxal (MG) \[µg/mg protein\]; * carboxyethyle(lysine) (CEL) \[µg/mg protein\]; * carbamyl protein groups \[µg/mg protein\] were assessed in the serum by competitive enzyme immunoassay (competitive ELISA) using kits from Cell Biolabs Inc, USA.

DIAGNOSTIC_TEST

selected electrolytes assessment

* potassium (K) \[mmol/l\]; * sodium (Na) \[mmol/l\]; * magnesium (Mg) \[mg/dL\] were assessed in the serum by routine techniques using Cobas Integra 400 plus biochemical analyzer by Roche Diagnostics, USA.

DIAGNOSTIC_TEST

NT-pro-brain natriuretic peptide (NT-proBNP)

NT-proBNP \[fmol/ml\] - was analyzed in the serum by enzyme immunoassay using the Nt-proBNP kit from Biomedica, Slovakia.

OTHER

estimated glomerular filtration rate (eGFR) calculation

eGFR \[ml/min/1.73m\^2\] - 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.

Sponsors & Collaborators

• Poznan University of Medical Sciences

  lead OTHER

Principal Investigators

• Dorota Formanowicz, MD, PhD · Poznan University of Mediccal Sciences

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-03-25

Primary Completion

2020-09-10

Completion

2020-09-30

Countries

• Poland

Study Locations