The Influence of Acute High Dose MitoQ on Urinary Kidney Injury Markers in Healthy Adults

Academic Article


  • INTRODUCTION: Mitochondrial-derived oxidative stress contributes to vascular dysfunction[1]. Chronic supplementation using the mitochondrial-targeted antioxidant, MitoQ, in low doses (20 mg/day), improves vascular function in older adults and patients with chronic kidney disease [2, 3]. Furthermore, multiple studies have used acute high dose (>80mg/day) MitoQ, to examine the influence of mitochondrial oxidative stress on the vasculature [3, 4]. However, recent in vitro data suggest that MitoQ may induce nephrotoxicity which could contribute to kidney damage[5]. Therefore, we sought to determine whether acute, high dose MitoQ elicited changes across multiple urinary biomarkers associated with kidney injury in healthy adults. METHODS: 15 healthy adults (10 females, mean ± SD, 28 ± 8 years, BMI: 25.3 ± 4.1 Kg/m2 , BP: 112 ± 13/67 ± 7 mmHg) reported to our laboratory for two separate visits and were assigned MitoQ (100 - 160 mg based on body mass) or a placebo, in a randomized crossover design. Visits were separated by ≥ 72 hours. Venous blood was collected at baseline (prior to capsule ingestion) and urine was collected for 4-6 hours after the study visits. We assessed serum and urine creatinine (Jaffe reaction) to determine 4-6-hour creatinine clearance. Regarding kidney injury biomarkers, we assessed multiple urinary biomarkers including the chitinase 3-like-1 gene product YKL-40, kidney-injury marker- 1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF), neutrophil gelatinase-associated lipocalin (NGAL), and uromodulin using multiplex. We calculated biomarker excretion rate (i.e., analyte concentration x 4-6-hour urine flow rate [ml/min]) and performed a natural log transformation prior to parametric testing. We used a paired sample t-test to compare creatinine clearance between conditions and Hotelling's T2 to assess urinary markers between conditions. RESULTS: There was a trend for acute MitoQ supplementation to reduce body surface area normalized creatinine clearance (placebo: 104.6 ± 16.6 vs MitoQ: 85.5 ± 24.4 mL/min/1.73m2 , p = 0.069, η = 0.699). However, acute MitoQ supplementation did not influence urine flow rate (placebo: 1.9 ± 1.2 vs MitoQ: 1.5 ± 0.8 ml/min, p = 0.333) or urinary kidney injury markers (T21,20 = 16.776, p = 0.151). Using exploratory univariate analysis there were not any trends for any individual urine kidney injury marker (e.g., YKL-40; placebo: 607 ± 386 vs. MitoQ 448 ± 241 pg/min, p = 0.544; KIM-1; placebo: 79.01 ± 38.14 vs MitoQ 69.72 ± 44.26 pg/min, p = 0.362; NGAL; placebo: 20.8 ± 16.8 vs. MitoQ 18.9 ± 21.3 ng/min, p = 0.470). CONCLUSIONS: Acute MitoQ supplementation reduced normalized creatinine clearance without influencing flow rate and had no effect on urinary kidney injury markers. Future studies should include patient populations and longer-term surveillance. However, based on our preliminary analysis using urinary kidney injury markers, acute high dose MitoQ supplementation does not elicit kidney injury in healthy adults.
  • Published In

  • The FASEB Journal  Journal
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    Author List

  • Linder BA; Barnett AM; Hutchison ZJ; Tharpe MA; Kavazis AN; Gutierrez OM; Robinson AT
  • Volume

  • 36