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Renal cortical thickness and PON1 activity both decrease in chronic renal failure
Gülçin Ak1, Mert Ozgönül, Eser Y Sözmen
1Ataturk Research and Educational Hospital, Department of Internal Medicine, Izmir, Turkey.
Background:
Chronic renal failure (CRF) is associated with a tendency to atherosclerosis due to the enhanced oxidative stress and insufficient antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and paraoxonase (PON 1), together with abnormalities in lipid parameters. We determined the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation and PON1 activities in patients with chronic renal insufficiency to see how PON1 affected the progression of the disease and whether hemodialysis influenced these parameters.
Methods:
Thirty-seven patients (21 men, 16 women, mean age 43.9 +/- 16) with CRF were included, 23 were receiving hemodialysis treatment. Exclusion criteria were diabetes mellitus and acute coronary disease. Eighteen healthy subjects (9 men and 9 women, mean age 39.9 +/- 10.5) volunteered to participate as controls. All patients were evaluated by renal ultrasound (USG) and two-dimensional echography, and their lipid profiles, PON1 activity, basal and Cu-induced LDL oxidation were determined.
Results:
PON1 activities of patients were lower than controls (14.4 +/- 11 vs 30.9 +/- 19 U/L, p < 0.05) while basal ox-LDL levels determined by the thiobarbituric acid reactive substances (TBARS) method were higher (0.6 +/- 0.4 vs 0.4+/- 0.2 nmol/mg LDL protein, p<0.01). There was no significant difference between the groups treated with hemodialysis or not. There was a positive correlation between renal cortical thickness and HDL levels (r=0.47, p=0.006) and PON1 activity (r=0.45, p=0.01).
Conclusion:
Our data showed that HDL cholesterol levels and PON1 activities were both lower in patients, indicating depletion of the protective antioxidant capacity. PON1 activities and phenotypes were no different in patients with coronary disease and others so it does not appear to be a significant indicator of coronary artery disease in patients with CRF.
Insights
Patients with chronic renal failure have lower antioxidant capacity due to reduced paraoxonase (PON 1) activity and HDL cholesterol levels. Hemodialysis did not significantly impact these markers, suggesting impaired defense against oxidative stress in chronic renal failure.
Area of Science:
- Biochemistry
- Nephrology
- Cardiovascular Research
Background:
- Chronic renal failure (CRF) is linked to atherosclerosis, heightened oxidative stress, and reduced antioxidant enzyme activity (e.g., superoxide dismutase, catalase, paraoxonase 1).
- Lipid profile abnormalities are common in CRF patients, contributing to cardiovascular risks.
Purpose of the Study:
- To investigate the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation in CRF patients.
- To assess paraoxonase 1 (PON1) activities in CRF patients and determine the influence of hemodialysis on these parameters.
- To explore the relationship between PON1 activity, LDL oxidation, and disease progression in CRF.
Main Methods:
- Studied 37 CRF patients (23 on hemodialysis) and 18 healthy controls, excluding diabetics and those with acute coronary disease.
- Evaluated lipid profiles, PON1 activity, and basal/copper-induced LDL oxidation using thiobarbituric acid reactive substances (TBARS).
- Utilized renal ultrasound and two-dimensional echocardiography for patient assessment.
Main Results:
- CRF patients exhibited significantly lower PON1 activities (14.4 U/L) compared to controls (30.9 U/L).
- Basal oxidized LDL (ox-LDL) levels were higher in CRF patients (0.6 nmol/mg LDL protein) versus controls (0.4 nmol/mg LDL protein).
- No significant differences in PON1 activity or LDL oxidation were observed between hemodialysis and non-hemodialysis CRF groups. Positive correlations found between renal cortical thickness and HDL levels/PON1 activity.
Conclusions:
- CRF patients demonstrate diminished antioxidant capacity, evidenced by lower HDL cholesterol and PON1 activities.
- PON1 activity and phenotypes did not appear to be significant indicators of coronary artery disease in this CRF cohort.
- The findings highlight impaired antioxidant defenses in CRF, irrespective of hemodialysis status.