Platelet Mitochondrial Respiration, Endogenous Coenzyme Q10 and Oxidative Stress in Patients with Chronic Kidney Disease

Anna Gvozdjáková, Zuzana Sumbalová, Jarmila Kucharská, Mária Komlósi, Zuzana Rausová, Oľga Vančová, Monika Számošová, Viliam Mojto, Anna Gvozdjáková, Zuzana Sumbalová, Jarmila Kucharská, Mária Komlósi, Zuzana Rausová, Oľga Vančová, Monika Számošová, Viliam Mojto

Abstract

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and a decrease of glomerular filtration rate. Reduced mitochondrial function, coenzyme Q10 (CoQ10), and increased oxidative stress in patients with CKD contribute to the disease progression. We tested whether CoQ10 levels, oxidative stress and platelet mitochondrial bioenergetic function differ between groups of CKD patients.

Methods: Twenty-seven CKD patients were enrolled in this trial, 17 patients had arterial hypertension (AH) and 10 patients had arterial hypertension and diabetes mellitus (AH and DM). The control group consisted of 12 volunteers. A high-resolution respirometry (HRR) method was used for the analysis of mitochondrial bioenergetics in platelets, and an HPLC method with UV detection was used for CoQ10 determination in platelets, blood, and plasma. Oxidative stress was determined as thiobarbituric acid reactive substances (TBARS).

Results: Platelets mitochondrial respiration showed slight, not significant differences between the groups of CKD patients and control subjects. The oxygen consumption by intact platelets positively correlated with the concentration of CoQ10 in the platelets of CKD patients.

Conclusion: A decreased concentration of CoQ10 and oxidative stress could contribute to the progression of renal dysfunction in CKD patients. The parameters of platelet respiration assessed by high-resolution respirometry can be used only as a weak biological marker for mitochondrial diagnosis and therapy monitoring in CKD patients.

Keywords: chronic kidney disease; coenzyme Q10; mitochondria; oxidative stress; platelets; respiration.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Respirometric analysis of mitochondrial function in human platelets. Legend: The trace from the measurement of platelet (PLT) respiration at 37 °C in a respiration medium MiR05 and 20 mM creatine. Blue line represents oxygen concentration (µM), and the red trace represents oxygen consumption as flow per cells (pmol O2 ∙ s−1 ∙10−6 cells). The modified (substrate-uncoupler-inhibitor-titration) SUIT reference protocol 1 (RP1) [22] includes following steps:
Figure 2
Figure 2
Platelet mitochondrial function in control subjects and groups of CKD patients. Legend: The parameters of mitochondrial respiration in human platelets. The bars show mean ± SEM. The names on the x-axis represent steps in the SUIT RP1—see the legend for Figure 1 in the Methods section. Control—the group of healthy subjects (n = 12); CKD-ALL—all patients with chronic kidney disease (n = 27); CKD and arterial hypertension (CKD+AH)—the subgroup of CKD-ALL patients with arterial hypertension (n = 17); and CKD+AH+diabetes mellitus (DM)—the subgroup of CKD-ALL patients with arterial hypertension and diabetes type 2 (n = 10).
Figure 3
Figure 3
Endogenous coenzyme Q10-TOTAL in platelets, blood, and plasma in control subjects and groups of CKD patients. Legend: coenzyme Q10 (CoQ10)-TOTAL (ubiquinol and ubiquinone); PLT—platelets; * p < 0.05; ** p < 0.01; and *** p < 0.001. Control—the group of healthy subjects (n = 12); CKD-ALL—all patients with chronic kidney disease (n = 27); CKD+AH—the subgroup of CKD-ALL patients with arterial hypertension (n = 17); CKD+AH+DM—the subgroup of CKD-ALL patients with arterial hypertension and diabetes type 2 (n = 10).
Figure 4
Figure 4
Correlation between CoQ10-TOTAL in platelets and the respiration of intact platelets in control subjects and CKD-ALL patients. Legend: ce1—the rate of oxygen consumption in intact platelet; CoQ10-TOTAL—ubiquinol and ubiquinone. CKD-ALL all patients with chronic kidney disease (n = 27); Control—the group of healthy subjects (n = 12). p < 0.05 statistically significant association between CoQ10-TOTAL in platelets and ce1 in CKD-ALL.
Figure 5
Figure 5
Correlation between thiobarbituric acid reactive substances (TBARS) and plasma CoQ10-TOTAL in control subjects and CKD-ALL patients. Legend: CoQ10-TOTAL—ubiquinol and ubiquinone. CKD-ALL—all patients with chronic kidney disease (n = 27); Control—the group of healthy subjects (n = 12).

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