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

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

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.

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.

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 smoking for at least 10 years in the history of
• no alcohol abuse for at least 10 years in a medical history,
• lack of diabetes and impaired fasting glucose and/or impaired glucose tolerance,
• 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, the following additional inclusion conditions were applied:

• 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.

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,
• 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.