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

Poznan University of Medical Sciences (PUMS)

Status: Completed

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

Treatments: Device: vessel stiffness assessment; Diagnostic Test: parameters of calcium and phosphate metabolism; Diagnostic Test: selected parameters of oxidative stress (1); Diagnostic Test: selected parameters of oxidative stress (2); Diagnostic Test: selected inflammatory markers; Other: cardiovascular (CV)-related death recording during 2-year follow-up; Diagnostic Test: parameters of lipids metabolism in the serum; Diagnostic Test: liver enzymes activity assessment; Device: non-invasive cardiological examinations; Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP); Diagnostic Test: creatinine and urea; Diagnostic Test: laboratory parameters - complete blood count; Diagnostic Test: selected parameters of oxidative stress (4) MG, CEL, carbamyl protein groups; Diagnostic Test: selected electrolytes assessment; Diagnostic Test: selected parameters of oxidative stress (3) sRAGE; Diagnostic Test: parameters of iron metabolism; Diagnostic Test: glucose (Glu); Other: body mass index (BMI) [kg/m^2] calculation; Diagnostic Test: metalloproteinases; Diagnostic Test: total protein and albumin; Device: carotid intima-media thickness (IMT); Diagnostic Test: fibroblast growth factor 23 (FGF-23); Other: estimated glomerular filtration rate (eGFR) calculation; Diagnostic Test: klotho

Study type: Observational

Funder types: Other

Identifiers

NCT05214872

PoznanUMS_DF2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 252 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

252 participants in 5 patient groups

PREDIALYSIS GROUP

Description:

(n = 48) - patients in the pre-dialysis period (stages G3b-G4 of chronic kidey disease (CKD)) with moderate or severe decrease in estimated glomerular filtration rate (eGFR) (eGFR 44-29 ml/min/1.73 m\^2)

Treatment:

Diagnostic Test: creatinine and urea

Diagnostic Test: selected parameters of oxidative stress (1)

Diagnostic Test: selected electrolytes assessment

Diagnostic Test: glucose (Glu)

Diagnostic Test: selected parameters of oxidative stress (2)

Diagnostic Test: metalloproteinases

Diagnostic Test: laboratory parameters - complete blood count

Diagnostic Test: parameters of calcium and phosphate metabolism

Diagnostic Test: selected inflammatory markers

Diagnostic Test: parameters of iron metabolism

Device: vessel stiffness assessment

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

Diagnostic Test: total protein and albumin

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

Device: carotid intima-media thickness (IMT)

Diagnostic Test: liver enzymes activity assessment

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

Other: estimated glomerular filtration rate (eGFR) calculation

Diagnostic Test: klotho

Diagnostic Test: selected parameters of oxidative stress (3) sRAGE

Diagnostic Test: parameters of lipids metabolism in the serum

Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP)

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

Device: non-invasive cardiological examinations

END-STAGE RENAL DISEASE (ESRD) GROUP

Description:

Patients with ESRD (n=106) - (eGFR \<15 ml/min /1.73 m\^2) undergoing renal replacement therapy have formed this group. Depending on the method of renal replacement therapy used, two subgroups have been distinguished: (1) peritoneal dialysis (PD) subgroup (n=35) including patients treated by peritoneal dialysis. In this subgroup, due to the treatment technique, two groups have been distinguished, a group (n=15) treated with the automatic peritoneal dialysis (APD) technique and a group (n = 20) using the technique of continuous cycling peritoneal dialysis (CCPD), (2) hemodialysis (HD) subgroup (n = 71) including patients treated with repeated hemodialysis. The duration of hemodialysis was at least 10 hours/week using standard bicarbonate dialysis fluids and polysulfone low-flux dialyzers. The blood flow during hemodialysis was 200-350 ml/min, with an average dialysis fluid flow of 500 ml/min.

Treatment:

Diagnostic Test: creatinine and urea

Diagnostic Test: selected parameters of oxidative stress (1)

Diagnostic Test: selected electrolytes assessment

Diagnostic Test: glucose (Glu)

Diagnostic Test: selected parameters of oxidative stress (2)

Diagnostic Test: metalloproteinases

Diagnostic Test: laboratory parameters - complete blood count

Diagnostic Test: parameters of calcium and phosphate metabolism

Diagnostic Test: selected inflammatory markers

Diagnostic Test: parameters of iron metabolism

Device: vessel stiffness assessment

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

Diagnostic Test: total protein and albumin

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

Device: carotid intima-media thickness (IMT)

Diagnostic Test: liver enzymes activity assessment

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

Other: estimated glomerular filtration rate (eGFR) calculation

Diagnostic Test: klotho

Diagnostic Test: selected parameters of oxidative stress (3) sRAGE

Diagnostic Test: parameters of lipids metabolism in the serum

Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP)

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

Device: non-invasive cardiological examinations

CARDIOLOGY (CARD) GROUP

Description:

CARD group (n = 37) - patients with at least one history of a cardiovascular event, admitted to hospital for elective angiography, without any signs of impaired kidney function. The studies in this group were conducted to check the changes that occur as a result of cardiovascular disease (CVD) but without kidney disease.

Treatment:

Diagnostic Test: creatinine and urea

Diagnostic Test: selected parameters of oxidative stress (1)

Diagnostic Test: selected electrolytes assessment

Diagnostic Test: glucose (Glu)

Diagnostic Test: selected parameters of oxidative stress (2)

Diagnostic Test: metalloproteinases

Diagnostic Test: laboratory parameters - complete blood count

Diagnostic Test: parameters of calcium and phosphate metabolism

Diagnostic Test: selected inflammatory markers

Diagnostic Test: parameters of iron metabolism

Device: vessel stiffness assessment

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

Diagnostic Test: total protein and albumin

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

Device: carotid intima-media thickness (IMT)

Diagnostic Test: liver enzymes activity assessment

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

Other: estimated glomerular filtration rate (eGFR) calculation

Diagnostic Test: klotho

Diagnostic Test: selected parameters of oxidative stress (3) sRAGE

Diagnostic Test: parameters of lipids metabolism in the serum

Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP)

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

Device: non-invasive cardiological examinations

Chronic kidney disease (CKD) 1-2 GROUP

Description:

CKD1-2 (n=29) (stage G1-G2 CKD) with mild decrease in eGFR (eGFR \>90-60 ml/min/1.73 m\^2) The studies in this group were performed to disclose the changes that occur as a consequence of the beginning of kidney function deterioration.

Treatment:

Diagnostic Test: creatinine and urea

Diagnostic Test: selected parameters of oxidative stress (1)

Diagnostic Test: selected electrolytes assessment

Diagnostic Test: glucose (Glu)

Diagnostic Test: selected parameters of oxidative stress (2)

Diagnostic Test: metalloproteinases

Diagnostic Test: laboratory parameters - complete blood count

Diagnostic Test: parameters of calcium and phosphate metabolism

Diagnostic Test: selected inflammatory markers

Diagnostic Test: parameters of iron metabolism

Device: vessel stiffness assessment

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

Diagnostic Test: total protein and albumin

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

Device: carotid intima-media thickness (IMT)

Diagnostic Test: liver enzymes activity assessment

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

Other: estimated glomerular filtration rate (eGFR) calculation

Diagnostic Test: klotho

Diagnostic Test: selected parameters of oxidative stress (3) sRAGE

Diagnostic Test: parameters of lipids metabolism in the serum

Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP)

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

Device: non-invasive cardiological examinations

Healthy volunteers (HV)

Description:

HV (n = 32) - this group was composed of healthy people, with no evidence of impairment in renal function and cardiovascular disorders in the history and at the time of enrollment in the study.

Treatment:

Diagnostic Test: creatinine and urea

Diagnostic Test: selected parameters of oxidative stress (1)

Diagnostic Test: selected electrolytes assessment

Diagnostic Test: glucose (Glu)

Diagnostic Test: selected parameters of oxidative stress (2)

Diagnostic Test: metalloproteinases

Diagnostic Test: laboratory parameters - complete blood count

Diagnostic Test: parameters of calcium and phosphate metabolism

Diagnostic Test: selected inflammatory markers

Diagnostic Test: parameters of iron metabolism

Device: vessel stiffness assessment

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

Diagnostic Test: total protein and albumin

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

Device: carotid intima-media thickness (IMT)

Diagnostic Test: liver enzymes activity assessment

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

Other: estimated glomerular filtration rate (eGFR) calculation

Diagnostic Test: klotho

Diagnostic Test: selected parameters of oxidative stress (3) sRAGE

Diagnostic Test: parameters of lipids metabolism in the serum

Diagnostic Test: NT-pro-brain natriuretic peptide (NT-proBNP)

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

Device: non-invasive cardiological examinations