Clinical trial NCT05214872: The Impact of Selected Factors on the Cardiovascular System in Chronic Kidney Disease
Official title: Assessment of the Impact of Selected Factors on the Cardiovascular System in Patients With Different Chronic Kidney Disease Stages
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atherosclerosis of Artery
Inflammation
Chronic Kidney Diseases
Dialysis; Complications
Cardiovascular Diseases
Keywords: risk factors
chronic kidney disease
inflammation
oxidative stress
atherosclerosis
mortality
Lead sponsor: Poznan University of Medical Sciences
Sponsor class: OTHER
First posted: 2022-01-31
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: A total of 252 people have been enrolled on the study, including 106 consecutive dialyzed patients (HD group), treated in 2016-2018 at the Nephrology Outpatient Clinic and the Clinical Hospital's Dialysis Center. H. Święcickiego in Poznań; 37 32 healthy participants (control group), serving as a comparative group.

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.

Eligibility criteria: Criteria:

The following criteria of qualifying for the study were adopted for all respondents:

* 18 years of age or older,
* written consent to participate in the study,
* no active inflammatory process,
* no neoplastic disease or a neoplastic disease whose treatment was stopped at least 10 years ago,
* no history of immunosuppressive treatment,
* stable liver function (not more than two times increased activity of transaminases), HBs antigen and anti-HCV negative antibodies,anti-HIV negative antibodies.

In addition, for CKD patients (CKD1-2) and PREDIALYSIS GROUP, the following additional inclusion conditions were applied:

* no acute cardiovascular complications, ie acute heart failure, hypertensive crisis, acute coronary syndrome, at the time of study entry.

At the same time, depending on the technique of renal replacement therapy used, additional inclusion criteria were established for each of the subgroups:

in group HD:

* a minimum of 6 months of treatment with repeated hemodialysis, 3 times a week, for a minimum of 10 hours a week,
* arteriovenous fistula as a vascular access for hemodialysis,
* Estimated dialysis adequacy ratio (eKt / V) of at least 1.2. in the PD group:
* treatment duration UP to a minimum of 6 months, Kt / V ≥1.8 l / week / 1.73 m2.

For CARD patients, additional conditions include:

* no obvious evidence of renal impairment in the history and at the time of study entry, renal function assessed on the basis of eGFR and urine albumin/creatinine ratio,
* history of angina pectoris,
* documented history of at least one acute coronary syndrome,
* admission to the Department of Intensive Care of Cardiology and Internal Diseases in order to perform a planned coronary angiography, on the day of admission to the study without signs of the acute coronary syndrome, no additional comorbidities, ie those that do not result directly or indirectly from coronary heart disease.

In turn, for the HV group (control group), additional conditions include:

* no obvious evidence of renal impairment in the history and at the time of study entry, renal function assessed on the basis of eGFR and urine albumin/creatinine ratio,
* no obvious signs of cardiovascular impairment in the history and at the time of study entry, estimated on the basis of normal blood pressure (\<140/90 mmHg), no abnormalities in the medical history and physical examination,
* not taking any medications on a regular basis.

Primary outcomes:
measure: Diagnostic test: basic biochemical parameters: complete blood count - hemoglobin (HGB)
timeFrame: 3 years
measure: Diagnostic test: basic biochemical parameters: complete blood count - red blood cell count (RBC)
timeFrame: 3 years
measure: Diagnostic test: basic biochemical parameters: complete blood count - hematocrit (HCT)
timeFrame: 3 years
measure: Diagnostic test: basic biochemical parameters: complete blood count - white blood cell count (WBC)
timeFrame: 3 years
measure: Diagnostic test: basic biochemical parameters: complete blood count - platelet count (PLT)
timeFrame: 3 years
measure: Diagnostic test: glucose (Glu)
timeFrame: 3 years
measure: Diagnostic test: urea
timeFrame: 3 years
measure: Diagnostic test: creatinine
timeFrame: 3 years
measure: Estimated glomerular filtration rate (eGFR) [ml/min/1.73m^2] calculation
timeFrame: 3 years
measure: Body mass index (BMI) [kg/m^2] calculation
timeFrame: 3 years
measure: Diagnostic test: parameters of lipids metabolism in the serum - total cholesterol (T-C)
timeFrame: 3 years
measure: Diagnostic test: parameters of lipids metabolism in the serum - high-density lipoprotein cholesterol (HDL-C)
timeFrame: 3 years
measure: Diagnostic test: parameters of lipids metabolism in the serum low-density lipoprotein cholesterol (LDL-C).
timeFrame: 3 years
measure: Diagnostic test: parameters of lipids metabolism in the serum - triglycerides (TG)
timeFrame: 3 years
measure: Diagnostic test: liver enzymes activity assessment - aspartate transaminase (AST)
timeFrame: 3 years
measure: Diagnostic test: liver enzymes activity assessment - alanine transaminase (ALT)
timeFrame: 3 years
measure: Diagnostic test: liver enzymes activity assessment - alkaline phosphatase (ALP) [U/l]
timeFrame: 3 years
measure: Diagnostic test: total protein (TP)
timeFrame: 3 years
measure: Diagnostic test: albumin(ALB)
timeFrame: 3 years
measure: Diagnostic test: parameters of iron metabolism - iron
timeFrame: 3 years
measure: Diagnostic test: parameters of iron metabolism - total iron-binding capacity (TIBC)
timeFrame: 3 years
measure: Diagnostic test: parameters of iron metabolism - the unsaturated iron-binding capacity (UIBC)
timeFrame: 3 years
measure: Diagnostic test: parameters of iron metabolism - ferritin
timeFrame: 3 years
measure: Diagnostic test: total and ionized calcium
timeFrame: 3 years
measure: Diagnostic test: phosphate
timeFrame: 3 years
measure: Diagnostic test: intact parathormone (iPTH)
timeFrame: 3 years
measure: Diagnostic test: klotho (KL)
timeFrame: 3 years
measure: Diagnostic test: fibroblast growth factor 23 (FGF-23)
timeFrame: 3 years
measure: Diagnostic test: selected electrolytes assessment in the serum: potassium (K) and sodium (Na)
timeFrame: 3 years
measure: Diagnostic test: selected electrolytes assessment in the serum: magnesium
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - 3-nitrotyrosine (3-NT)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - advanced glycation ends products (AGE)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - carboxymethyle(lysine) (CML)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - advanced oxidation protein products (AOPP)
timeFrame: 3 years
measure: Diagnostic test: metalloproteinases - metalloproteinase 9 (MMP-9)
timeFrame: 3 years
measure: Diagnostic test: metalloproteinases - tissue inhibitor of metalloproteinase 1 (TIMP-1)
timeFrame: 3 years
measure: The MMP-9/TIMP-1 ratio assessment
timeFrame: 3 years
measure: Diagnostic test: selected inflammatory markers - high-sensivity C-reactive protein (hsCRP)
timeFrame: 3 years
measure: Diagnostic test: selected inflammatory markers - neopterin
timeFrame: 3 years
measure: Diagnostic Test: selected inflammatory markers - interleukin 18 (IL-18)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - myeloperoxidase (MPO)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - methylglyoxal (MG)
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - carboxyethyle(lysine) (CEL) [µg/mg protein]
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - carbamyl protein groups [µg/mg protein]
timeFrame: 3 years
measure: Diagnostic test: selected parameters of oxidative stress - soluble receptor for advanced glycation end products (sRAGE)
timeFrame: 3 years
measure: 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
timeFrame: 3 years
measure: 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)
timeFrame: 3 years
measure: 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)
timeFrame: 3 years
measure: Device: carotid intima-media thickness (IMT)
timeFrame: 3 years
measure: Device: vessel stiffness assessments - reflection index (RI)
timeFrame: 3 years
measure: Device: vessel stiffness assessments - vascular stiffness index (SI)
timeFrame: 3 years
measure: Device: vessel stiffness assessments - peripheral (pPP) and central pulse pressure (cPP) [mm Hg]
timeFrame: 3 years
measure: Device: vessel stiffness assessments - peripheral pulse pressure/central pulse pressure (pPP/cPP) ratio
timeFrame: 3 years
measure: Cardiovascular (CV)-related death recording during 2-year follow-up
timeFrame: 2 years for each person qualified for the study
measure: Diagnostic test: N-terminal pro-B-type natriuretic peptide (NT-proBNP)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Poznań
country: Poland
facility: Poznan University of Medical Sciences
Study officials:
affiliation: Poznan University of Mediccal Sciences
name: Dorota Formanowicz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Twardawa M, Formanowicz P, Formanowicz D. Chronic Kidney Disease as a Cardiovascular Disorder-Tonometry Data Analyses. Int J Environ Res Public Health. 2022 Sep 28;19(19):12339. doi: 10.3390/ijerph191912339.
citation: Kasprzak L, Twardawa M, Formanowicz P, Formanowicz D. The Mutual Contribution of 3-NT, IL-18, Albumin, and Phosphate Foreshadows Death of Hemodialyzed Patients in a 2-Year Follow-Up. Antioxidants (Basel). 2022 Feb 11;11(2):355. doi: 10.3390/antiox11020355.