Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Issue 9 (9th May 2016)

• Record Type: Journal Article
• Authors: Gamboa, Jorge L.; Billings, Frederic T.; Bojanowski, Matthew T.; Gilliam, Laura A.; Yu, Chang; Roshanravan, Baback; Roberts, L. Jackson; Himmelfarb, Jonathan; Ikizler, T. Alp; Brown, Nancy J.
• Is Part Of: Physiological reports. Volume 4:Issue 9(2016:May)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-05-09
• Subjects: BNIP3 -- chronic kidney disease -- mitochondria -- mitochondrial DNA copy number -- oxidative stress -- PGC1α -- skeletal muscle; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12780
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD. Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1 α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2‐isoprostanes in 208 subjects divided into three groups: non‐CKD (eGFR>60 mL/min), CKD stage 3–4 (eGFR 60–15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non‐CKD (6.48, 95% CI 4.49–8.46), CKD stage 3–4 (3.30, 95% CI 0.85–5.75, P = 0.048 vs. non‐CKD), and CKD stage 5 (1.93, 95% CI 0.27–3.59, P = 0.001 vs. non‐CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76–95.36) compared to patients with non‐CKD (median 49.95 pg/mL, IQR 27.88–83.46, P = 0.001), whereas F2‐isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD. Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages. Abstract : We present data showing for the very first time that the number of mitochondria is diminished in skeletal muscle biopsies from patients on maintenance hemodialysis. We also confirmed the presence of ultrastructure abnormalities in skeletal muscle mitochondria in patients on hemodialysis. We also found that markers of mitochondrial dysfunction are commonly present in patients with chronic kidney disease, and these markers can be detected in blood samples.