Objective  To investigate the impact and related mechanisms of L-carnitine on lipid metabolism, microinflammation, and oxidative stress status in hemodialysis patients with chronic kidney disease, and explore the potential mechanisms.

Methods  The data of patients with chronic kidney disease receiving dialysis admitted to Xingtai People's Hospital from January 2022 to January 2023 were collected, and they were divided into levocanidin group (levocanidin+conventional treatment) and conventional treatment group. The two groups were compared in terms of treatment safety and renal function indexes [blood creatinine (Scr) and urea nitrogen (BUN)], lipid metabolism status [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and serum free carnitine (FC)], microinflammatory markers [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP)] and oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)].

Results  A total of 120 patients were included in the study, with 60 in each group. After 6 months of treatment, there was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05), but the Scr and BUN of the patients in the levocanidin group were lower than those in the conventional treatment group (P<0.05), and the therapeutic efficacy rate was higher than that in the conventional treatment group (P<0.05). Regarding lipid metabolic status, serum TC, TG, LDL-C and ApoB levels of patients in the levocanitine group decreased compared with those before treatment (P<0.05), while serum ApoA1 and FC were elevated (P<0.05); and serum ApoB levels of patients in the conventional treatment group decreased compared with those before treatment (P<0.05). The levels of TC, TG, LDL-C and ApoB were significantly lower and the levels of ApoA1 and FC were significantly higher in the leucovorin group than in the conventional treatment group (P<0.05), whereas there was no significant difference in the levels of serum HDL-C (P>0.05). In terms of microinflammatory status, IL-6, IL-8, TNF-α, and CRP levels decreased in both groups compared with those before treatment (P<0.05), but IL-6, IL-8, TNF-α, and CRP levels of patients in the leucovorin group were significantly lower than those in the conventional treatment group (P<0.05). As for the oxidative stress indexes, the SOD and MDA levels of patients in both groups decreased (P<0.05), while the GSH-Px levels increased (P<0.05) compared with the pretreatment; and compared with the conventional treatment group, patients in the levocanitine group had higher levels of GSH-Px, and lower levels of SOD and MDA (P<0.05).

Conclusion  The use of L-carnitine may further ameliorate microinflammation and oxidative stress by improving lipid metabolism in dialysis patients with chronic kidney disease.

1.中华预防医学会肾脏病预防与控制专业委员会. 中国慢性肾脏病早期评价与管理指南[J]. 中华内科杂志, 2023, 62(8): 902-930. DOI: 10.3760/cma.j.cn112138-20221013-00755.

2.Lo R, Narasaki Y, Lei S, et al. Management of traditional risk factors for the development and progression of chronic kidney disease[J]. Clin Kidney J, 2023, 16(11): 1737-1750. DOI: 10.1093/ckj/sfad101.

3.Thompson S, James M, Wiebe N, et al. Cause of death in patients with reduced kidney function[J]. J Am Soc Nephrol, 2015, 26(10): 2504-2511. DOI: 10.1681/ASN.2014070714.

4.Noels H, Lehrke M, Vanholder R, et al. Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations[J]. Nat Rev Nephrol, 2021, 17(8): 528-542. DOI: 10.1038/s41581-021-00423-5.

5.任一鸣, 张晋辉, 王聪聪, 等. Toll样受体在钙化性主动脉瓣疾病中的研究进展[J]. 医学新知, 2024, 34(2): 217-225. [Ren YM, Zhang JH, Wang CC, et al. Research progress on toll-like receptors in calcific aortic valve disease[J]. Yixue Xinzhi Zazhi, 2024, 34(2): 217-225.] DOI: 10.12173/j.issn.1004-5511.202312035.

6.Kruger C, Nguyen TT, Breaux C, et al. Proximal tubular cell-specific ablation of carnitine acetyltransferase causes tubular disease and secondary glomerulosclerosis[J]. Diabetes, 2019, 68(4): 819-831. DOI: 10.2337/db18-0090.

7.Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, et al. Significance of l-carnitine for human health[J]. IUBMB Life, 2017, 69(8): 578-594. DOI: 10.1002/iub.1646.

8.Evans AM, Fornasini G. Pharmacokinetics of L-carnitine[J]. Clin Pharmacokinet, 2003, 42(11): 941-967. DOI: 10.2165/00003088-200342110-00002.

9.Nishioka N, Luo Y, Taniguchi T, et al. Carnitine supplements for people with chronic kidney disease requiring dialysis[J]. Cochrane Database Syst Rev, 2022, 12(12): CD013601. DOI: 10.1002/14651858.CD013601.pub2.

10.Rastgoo S, Fateh ST, Nikbaf-Shandiz M, et al. The effects of L-carnitine supplementation on inflammatory and anti-inflammatory markers in adults: a systematic review and dose-response meta-analysis[J]. Inflammopharmacology, 2023, 31(5): 2173-2199. DOI: 10.1007/s10787-023-01323-9.

11.王安世, 万菁菁, 朱丽君, 等. 不同营养素干预对衰弱老年人身体物理机能影响的网状Meta分析[J]. 中 国循证医学杂志, 2023, 23(3): 303-310. [Wang AS, Wan  JJ, Zhu LJ, et al. Network Meta-analysis of the effects of different nutrient interventions on physical function in frail elderly people[J]. Chinese Journal of Evidence-Based Medicine, 2023, 23(3): 303-310.] DOI: 10.7507/1672-2531.202207155.

12.Virmani MA, Cirulli M. The role of l-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation[J]. Int J Mol Sci, 2022, 23(5): 2717. DOI: 10.3390/ijms23052717.

13.Feng Y, Guo C, Wei J, et al. Necessity of carnitine supplementation in semistarved rats fed a high-fat diet[J]. Nutrition, 2001, 17(7-8): 628-631. DOI: 10.1016/s0899-9007(01)00601-3.

14.Mihai S, Codrici E, Popescu ID, et al. Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome[J]. J Immunol Res, 2018, 2018: 2180373. DOI: 10.1155/2018/2180373.

15.Sharma B, Yadav DK. L-carnitine and chronic kidney disease: a comprehensive review on nutrition and health perspectives[J]. J Pers Med, 2023, 13(2): 298. DOI: 10.3390/jpm13020298.

16.叶彬彬, 杨恺, 杜艳. 代谢组学在糖尿病肾病早期诊断中的研究进展[J]. 华西医学, 2023, 38(4): 603-607. [Ye  BB, Yang K, Du Y. Research progress of metabonomics in early diagnosis of diabetic kidney disease[J]. West China Medicine, 2023, 38(4): 603-607.] DOI: 10.7507/1002-0179.202211039.

17.Tanaka Y, Sasaki R, Fukui F, et al. Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats[J]. J Lipid Res, 2004, 45(4): 729-735. DOI: 10.1194/jlr.M300425-JLR200.

18.Lopez F, Hernandez F, Urbina JA. L-carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets[J]. Lipids, 2000, 35(6): 627-632. DOI: 10.1007/s11745-000-0566-2.

19.Muscella A, Stefàno E, Marsigliante S. The effects of exercise training on lipid metabolism and coronary heart disease[J]. Am J Physiol Heart Circ Physiol, 2020, 319(1): H76-H88. DOI: 10.1152/ajpheart.00708.2019.

20.M AK, Mantan M, Mahajan B. Serum apolipoproteins (Apo A-1, Apo B, and Apo B/Apo A-1 ratio) for early identification of dyslipidemia in children with CKD[J]. Pediatr Nephrol, 2024, 39(3): 849-856. DOI: 10.1007/s00467-023-06144-0.

21.Sato Y, Fujimoto S, Toida T, et al. Apoprotein B/Apoprotein A-1 ratio and mortality among prevalent dialysis patients[J]. Clin J Am Soc Nephrol, 2016, 11(5): 840-846. DOI: 10.2215/CJN.09830915.

22.Farag A, Elfadadny A, Mandour AS, et al. Potential protective effects of L-carnitine against myocardial ischemia/reperfusion injury in a rat model[J]. Environ Sci Pollut Res Int, 2024, 31(12): 18813-18825. DOI: 10.1007/s11356-024-32212-5.

23.Yang T, Liu S, Ma H, et al. Carnitine functions as an enhancer of NRF2 to inhibit osteoclastogenesis via regulating macrophage polarization in osteoporosis[J]. Free Radic Biol Med, 2024, 213: 174-189. DOI: 10.1016/j.freeradbiomed.2024.01.017.

24.Chisty TTE, Sarif S, Jahan I, et al. Protective effects of L-carnitine on isoprenaline-induced heart and kidney dysfunctions: modulation of inflammation and oxidative stress-related gene expression in rats[J]. Heliyon, 2024, 10(3): e25057. DOI: 10.1016/j.heliyon.2024.e25057.

25.Caballero-García A, Noriega-González DC, Roche E, et al. Effects of L-carnitine intake on exercise-induced muscle damage and oxidative stress: a narrative scoping review[J]. Nutrients, 2023, 15(11): 2587. DOI: 10.3390/nu15112587.

26.Kang HM, Ahn SH, Choi P, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development[J]. Nat Med, 2015, 21(1): 37-46. DOI: 10.1038/nm.3762.

27.Tölle M, Huang T, Schuchardt M, et al. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A[J]. Cardiovasc Res, 2012, 94(1): 154-162. DOI: 10.1093/cvr/cvs089.

28.Luo M, Liu A, Wang S, et al. ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity[J]. Sci Rep, 2017, 7(1): 2312. DOI: 10.1038/s41598-017-02601-7.

29.Soppert J, Lehrke M, Marx N, et al. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting[J]. Adv Drug Deliv Rev, 2020, 159: 4-33. DOI: 10.1016/j.addr.2020.07.019.

30.Bancells C, Sánchez-Quesada JL, Birkelund R, et al. HDL and electronegative LDL exchange anti- and pro-inflammatory properties[J]. J Lipid Res, 2010, 51(10): 2947-2956. DOI: 10.1194/jlr.M005777.

31.张欣欣, 许旻, 陈晓婷, 等. 抗氧化活性物质对心肌缺血再灌注损伤的保护机制研究进展[J].中国药师, 2022, 25(8): 1436-1442. [Zhang XX, Xu M, Chen XT, et al. Research progress on the protective mechanisms of antioxidants against myocardial ischemia-reperfusion injury[J]. China Pharmacist, 2022, 25(8): 1436-1442.] DOI: 10.19962/j.cnki.issn1008-049X.2022.08.026.