Assessment of Protein Modification in Chronic Kidney Disease - Selected Clinical and Biochemical Aspects

NCT ID: NCT04939870

Last Updated: 2021-12-10

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 195 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-01
• Study Completion Date: 2019-01-10

Brief Summary

The studies included the effect of chronic kidney disease advancement on the accumulation of oxidative stress markers in plasma. In patients with end-stage renal disease, the effect of replacement therapy was also assessed. Therefore, the patient with chronic kidney disease was evaluated divided into three groups (chronic kidney disease at stage G3b-G4, peritoneal dialysis, hemodialysis). In addition, changes in the interrelationship between oxidative modifications, carbonyl and nitrogen stress, and the carbamylation resulting from the progression of kidney disease have been taken into account. This issue is related to the assessment of whether the protein modification types differentiate patients depending on the stage of chronic kidney disease and the method of renal replacement therapy. Protein modifications associated with oxidative stress are a part of the complications resulting from chronic kidney diseases, such as malnutrition, chronic inflammation, dyslipidemia, iron disorder, and calcium and phosphate disorders. Also, diseases of atherosclerosis aetiology are much higher frequency in patients with chronic kidney disease than in those with normal kidney function. Therefore, in the studies presented here, particular attention was paid to the effect of oxidative stress on chronic kidney disease complications in the aspect of cardiovascular damage. The specificity of atherosclerosis in patients with chronic kidney disease was evaluated by comparing groups of this type of patients with patients with ischemic heart diseases and normal renal function.

Detailed Description

Redox imbalance in the course of CKD results in the intensification of oxidative and carbonyl stress, which leads to the modification of many molecules, including proteins necessary for the proper functioning of the body. The assessment of the accumulation of modified proteins in the plasma is not only an indirect indicator of the severity of redox imbalance in the system, but also allows the analysis of the influence of oxidative stress and its derivatives (glycation, carbonyl stress and carbamylation) on the pathogenesis of CKD. In addition, compounds formed as a result of the action of ROS on proteins may affect the development of long-term consequences of CKD, such as chronic inflammation, dyslipidemia, renal osteodystrophy, iron metabolism disorders and malnutrition. On the other hand, complications in patients with CKD may influence the intensification of oxidative modifications of proteins.

The following goals were set in the study:

1. Assessment of the impact of CKD advancement on the severity of protein modification as a result of oxidative stress.

2. Comparison of the effect of renal replacement therapy on protein modifications.

3. Assessment of the relationship between selected protein modifications in CKD and complications typical of CKD

4. Comparison of selected protein modifications in patients with CKD and patients with at least one history of a cardiovascular event.

Conditions

Chronic Kidney Diseases; Cardiovascular Diseases; Dialysis; Complications

Keywords

oxidative stress, proteins, chronic kidney disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

PREDIALYSIS GROUP

(n = 48) - patients in the pre-dialysis period (stage G3b-G4 CKD) with moderate or severe decrease in eGFR (eGFR 44-29 ml / min / 1.73 m2),

Biochemical parameters evaluation

Intervention Type: DIAGNOSTIC_TEST

selected biochemical parameters

END-STAGE RENAL DISEASE GROUP

patients with ESRD (n=78) - (eGFR \<15 ml/min /1.73 m2) undergoing renal replacement therapy. Depending on the method of renal replacement therapy used, two subgroups are distinguished: PD subgroup (n=35) including patients treated by peritoneal dialysis. In this subgroup, initially, due to the treatment technique, two groups were separated, a group (n=15) treated with the automatic peritoneal dialysis (APD) technique, and a group of patients (n = 20) using the technique of continuous cycling peritoneal dialysis (CCPD), HD subgroup (n = 43) including patients treated with repeated hemodialysis. Hemodialysis procedures were performed in each patient three times a week, via an arteriovenous fistula from own or artificial vessels. 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.

Biochemical parameters evaluation

Intervention Type: DIAGNOSTIC_TEST

selected biochemical parameters

CARDIOLOGY GROUP

• CARD group (n = 37) - patients with at least one history of cardiovascular events, admitted to hospital for elective angiography, without any signs of impaired kidney function. The studies in this group were to show the changes that occur as a result of diseases of the cardiovascular system and the functioning of the kidneys.

Biochemical parameters evaluation

Intervention Type: DIAGNOSTIC_TEST

selected biochemical parameters

HEALTHY VOLUNTEERS

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

Biochemical parameters evaluation

Intervention Type: DIAGNOSTIC_TEST

selected biochemical parameters

Interventions

Biochemical parameters evaluation

selected biochemical parameters

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• no additional comorbidities that do not result directly or indirectly from CKD,
• no acute cardiovascular complications, ie acute heart failure, hypertensive crisis, acute coronary syndrome, at the time of study entry.

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,
• 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 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, 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Poznan University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Dorota Formanowicz

MD.Ph.D. Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dorota Formanowicz, MD,PhD,Prof

Role: PRINCIPAL_INVESTIGATOR

Poznan University of Mediccal Sciences

Locations

Poznan University of Medical Sciences

Poznan, , Poland

Countries

Poland

Other Identifiers

PoznanUMS_DF_1

Identifier Type: -

Identifier Source: org_study_id