Ahmadi Armin, Valencia Ana P, Begue Gwénaëlle, Norman Jennifer E, Fan Sili, Durbin-Johnson Blythe P, Jenner Bradley N, Campbell Matthew D, Reyes Gustavo, Kapahi Pankaj, Himmelfarb Jonathan, de Boer Ian H, Marcinek David J, Kestenbaum Bryan R, Gamboa Jorge L, Roshanravan Baback
Division of Nephrology, Department of Medicine, University of California, Davis, California.
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington.
Clin J Am Soc Nephrol. 2025 Mar 1;20(3):346-357. doi: 10.2215/CJN.0000000624. Epub 2025 Jan 23.
Nicotinamide riboside and coenzyme Q10 supplementation showed distinct beneficial effects on whole-blood transcriptome, inflammatory cytokines, and oxidative stress. Nicotinamide riboside treatment altered the expression of genes associated with metabolism and immune response coinciding with a decrease in markers of oxidative stress. Coenzyme Q10 supplementation altered genes associated with lipid metabolism coinciding with reductions in markers of oxidative stress and inflammatory cytokines.
Mitochondria-driven oxidative/redox stress and inflammation play a major role in CKD pathophysiology. Compounds targeting mitochondrial metabolism may improve mitochondrial function, inflammation, and redox stress; however, there is limited evidence of their efficacy in CKD.
We conducted a pilot, randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/d of coenzyme Q10 (CoQ10) or 1000 mg/d of nicotinamide riboside (NR) supplementation with placebo in 25 patients with moderate-to-severe CKD (eGFR <60 ml/min per 1.73 m). We assessed changes in blood transcriptome using 3′-Tag-Seq gene expression profiling and changes in prespecified secondary outcomes of inflammatory and oxidative stress biomarkers. For a subsample of participants (=14), we assessed lymphocyte and monocyte bioenergetics using an extracellular flux analyzer.
The (mean±SD) age, eGFR, and body mass index of the participants were 61±11 years, 37±9 ml/min per 1.73 m, and 28±5 kg/m, respectively. Of the participants, 16% had diabetes and 40% were female. Compared with placebo, NR-mediated transcriptomic changes were enriched in gene ontology terms associated with carbohydrate/lipid metabolism and immune signaling, whereas CoQ10 changes were enriched in immune/stress response and lipid metabolism gene ontology terms. NR increased plasma IL-2 (estimated difference, 0.32; 95% confidence interval [CI], 0.14 to 0.49 pg/ml), and CoQ10 decreased both IL-13 (estimated difference, −0.12; 95% CI, −0.24 to −0.01 pg/ml) and C-reactive protein (estimated difference, −0.11; 95% CI, −0.22 to 0.00 mg/dl) compared with placebo. Both NR and CoQ10 reduced five-series F2-isoprostanes (estimated difference, −0.16 and −0.11 pg/ml, respectively; < 0.05 for both). NR, but not CoQ10, increased the Bioenergetic Health Index (estimated difference, 0.29; 95% CI, 0.06 to 0.53) and spare respiratory capacity (estimated difference, 3.52; 95% CI, 0.04 to 7 pmol/min per 10,000 cells) in monocytes.
Six weeks of NR and CoQ10 improved markers of oxidative stress, inflammation, and cell bioenergetics in patients with moderate-to-severe CKD.
: NCT03579693.
补充烟酰胺核糖苷和辅酶Q10对全血转录组、炎性细胞因子和氧化应激显示出明显的有益作用。烟酰胺核糖苷治疗改变了与代谢和免疫反应相关基因的表达，同时氧化应激标志物减少。补充辅酶Q10改变了与脂质代谢相关的基因，同时氧化应激标志物和炎性细胞因子减少。
线粒体驱动的氧化/氧化还原应激和炎症在慢性肾脏病（CKD）病理生理学中起主要作用。针对线粒体代谢的化合物可能改善线粒体功能、炎症和氧化还原应激；然而，其在CKD中疗效的证据有限。
我们进行了一项前瞻性、随机、双盲、安慰剂对照的交叉试验，比较25例中重度CKD（估算肾小球滤过率[eGFR]<60 ml/min/1.73 m²）患者每天补充1200 mg辅酶Q10（CoQ10）或1000 mg烟酰胺核糖苷（NR）与安慰剂的效果。我们使用3′-标签序列基因表达谱评估血液转录组的变化，以及炎性和氧化应激生物标志物的预设次要结局的变化。对于一部分参与者（n = 14），我们使用细胞外流量分析仪评估淋巴细胞和单核细胞的生物能量学。
参与者的（均值±标准差）年龄、eGFR和体重指数分别为61±11岁、37±9 ml/min/1.73 m²和28±5 kg/m²。参与者中，16%患有糖尿病，40%为女性。与安慰剂相比，NR介导的转录组变化在与碳水化合物/脂质代谢和免疫信号相关的基因本体术语中富集，而CoQ10的变化在免疫/应激反应和脂质代谢基因本体术语中富集。与安慰剂相比，NR增加了血浆白细胞介素-2（IL-2）（估计差异为0.32；95%置信区间[CI]，0.14至0.49 pg/ml），CoQ10降低了IL-13（估计差异为−0.12；95%CI，−0.24至−0.01 pg/ml）和C反应蛋白（估计差异为−0.11；95%CI，−0.22至0.00 mg/dl）。NR和CoQ10均降低了五系F2-异前列腺素（估计差异分别为−0.16和−0.11 pg/ml；两者均P<0.05）。NR增加了单核细胞的生物能量健康指数（估计差异为0.29；95%CI，0.06至0.53）和备用呼吸能力（估计差异为3.52；95%CI，0.04至7 pmol/min/10000个细胞），而CoQ10没有。
6周的NR和CoQ10改善了中重度CKD患者的氧化应激、炎症和细胞生物能量学标志物。
NCT03579693。
