Open AccessMitochondrial dysfunction and oxidative stress in patients with chronic kidney disease
Author(s) -
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.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12780
Subject(s) - kidney disease , medicine , oxidative stress , hemodialysis , sarcopenia , mitochondrion , endocrinology , renal function , peripheral blood mononuclear cell , skeletal muscle , stage (stratigraphy) , gastroenterology , pathology , biology , biochemistry , paleontology , in vitro , microbiology and biotechnology
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 (mt DNA ) copy number, BNIP 3, and PGC 1 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 mt DNA copy number in peripheral blood mononuclear cells ( PBMC s), 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 mt DNA copy number, and higher BNIP 3 content than controls. mt DNA copy number in PBMC s 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.