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

Abstract

IntroductionMitochondrial‐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.Methods15 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.ResultsThere 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).ConclusionsAcute 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.