非酒精性脂肪性肝病与慢性肾病关系的研究进展
DOI: 10.3969/j.issn.1001-5256.2022.11.030
Research advances in the relationship between nonalcoholic fatty liver disease and chronic kidney disease
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摘要: 越来越多的研究表明非酒精性脂肪性肝病(NAFLD)与慢性肾病(CKD)紧密相关。虽然其中的因果关联还未能阐明,但代谢失调、饮食-肠道菌群轴失调、氧化应激、血小板激活、遗传学与表观遗传学调控等机制在疾病交互网络中起到了重要作用。本文在综述NAFLD与CKD之间关联证据、NAFLD以及与NAFLD密切相关的因素可能增加CKD发生风险的潜在机制基础上,一并提出了患者管理建议及治疗策略。Abstract: More and more studies have shown that nonalcoholic fatty liver disease (NAFLD) is closely associated with chronic kidney disease (CKD). Although the causal relationship has not been clarified, the mechanisms, such as metabolic disorders, diet-intestinal microbiota axis disorders, oxidative stress, platelet activation, and genetic and epigenetic regulation, play an important role in the disease interaction network. This article reviews the evidence for the association between NAFLD and CKD and the potential mechanisms under which NAFLD and its related factors may increase the risk of CKD, and moreover, it proposes related patient management recommendations and treatment strategies.
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Key words:
- Non-alcoholic Fatty Liver Disease /
- Nephrosis /
- Pathologic Processes
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表 1 建议用于NAFLD患者肾功能评估的监测指标及优缺点
Table 1. Recommended monitoring indicators and their advantages or disadvantages for renal function evaluation in NAFLD patients
监测指标 优点 缺点 血清肌酐 经济便捷 受年龄、性别、肌肉含量、饮食、运动、种族、溶血等因素影响 尿素氮 经济便捷 受出血、肝功能、营养水平影响 尿蛋白 经济 24 h尿标本收集不便,受年龄、性别、运动、肌肉含量、妊娠等因素影响 随机尿白蛋白/肌酐比值 经济便捷 受感染、发热、显著高血糖、未控制的高血压、运动、心力衰竭、月经等因素影响 GFR 金标准 复杂、昂贵、侵入性检查 基于血清肌酐的eGFR计算公式 Cockcroft-Gault公式 经济便捷 受年龄、性别、肌肉含量、饮食、运动、种族、溶血等因素影响,且极端体质量人群中不准确 肾脏病饮食改良公式 经济便捷,不受体质量影响 受年龄、性别、肌肉含量、饮食、运动、种族、溶血等因素影响 CKD-EPI公式 经济便捷 受年龄、性别、肌肉含量、饮食、运动、种族、溶血等因素影响 基于血清肌酐与胱抑素C的eGFR计算公式 CKD-EPI胱抑素C公式 经济便捷,较单独基于血清肌酐的公式计算eGFR更加精准 基于中国人的胱抑素C公式有待开发 CKD-EPI肌酐-胱抑素C公式 经济便捷,诊断精确性较此前临床常用的传统公式高 肝硬化与非肝硬化患者相比,对前者肾功能的评估准确性稍差 注:CKD-EPI,CKD流行病学合作研究。 -
[1] ZHU LY, LI YC, DENG LH, et al. Research advances in extrahepatic diseases associated with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2021, 37(9): 2215-2219. DOI: 10.3969/j.issn.1001-5256.2021.09.043.朱蕗颖, 李雨晨, 邓利华, 等. 非酒精性脂肪性肝病相关肝外疾病的研究进展[J]. 临床肝胆病杂志, 2021, 37(9): 2215-2219. DOI: 10.3969/j.issn.1001-5256.2021.09.043. [2] WANG TY, WANG RF, BU ZY, et al. Association of metabolic dysfunction-associated fatty liver disease with kidney disease[J]. Nat Rev Nephrol, 2022, 18(4): 259-268. DOI: 10.1038/s41581-021-00519-y. [3] LV JC, ZHANG LX. Prevalence and disease burden of chronic kidney disease[J]. Adv Exp Med Biol, 2019, 1165: 3-15. DOI: 10.1007/978-981-13-8871-2_1. [4] TARGHER G, CHONCHOL M, BERTOLINI L, et al. Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease[J]. J Am Soc Nephrol, 2008, 19(8): 1564-1570. DOI: 10.1681/ASN.2007101155. [5] TARGHER G, MANTOVANI A, PICHIRI I, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes[J]. Diabetes Care, 2014, 37(6): 1729-1736. DOI: 10.2337/dc13-2704. [6] SEO DH, SUH YJ, CHO Y, et al. Advanced liver fibrosis is associated with chronic kidney disease in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease[J]. Diabetes Metab J, 2022, 46(4): 630-639. DOI: 10.4093/dmj.2021.0130. [7] KAPS L, LABENZ C, GALLE PR, et al. Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease[J]. United European Gastroenterol J, 2020, 8(8): 942-948. DOI: 10.1177/2050640620944098. [8] AKAHANE T, AKAHANE M, NAMISAKI T, et al. Association between non-alcoholic fatty liver disease and chronic kidney disease: A cross-sectional study[J]. J Clin Med, 2020, 9(6): 1635. DOI: 10.3390/jcm9061635. [9] MANTOVANI A, PETRACCA G, BEATRICE G, et al. Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis[J]. Gut, 2022, 71(1): 156-162. DOI: 10.1136/gutjnl-2020-323082. [10] LI M, ZHAO Z, QIN G, et al. Non-alcoholic fatty liver disease, metabolic goal achievement with incident cardiovascular disease and eGFR-based chronic kidney disease in patients with prediabetes and diabetes[J]. Metabolism, 2021, 124: 154874. DOI: 10.1016/j.metabol.2021.154874. [11] LIU HW, LIU JS, KUO KL. Association of nonalcoholic fatty liver and chronic kidney disease: An analysis of 37, 825 cases from health checkup center in Taiwan[J]. Tzu Chi Med J, 2020, 32(1): 65-69. DOI: 10.4103/tcmj.tcmj_233_18. [12] CAI X, SUN L, LIU X, et al. Non-alcoholic fatty liver disease is associated with increased risk of chronic kidney disease[J]. Ther Adv Chronic Dis, 2021, 12: 20406223211024361. DOI: 10.1177/20406223211024361. [13] ZHANG M, LIN S, WANG MF, et al. Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?[J]. BMC Gastroenterol, 2020, 20(1): 139. DOI: 10.1186/s12876-020-01278-z. [14] ESLAM M, SANYAL AJ, GEORGE J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014. DOI: 10.1053/j.gastro.2019.11.312. [15] SUN DQ, JIN Y, WANG TY, et al. MAFLD and risk of CKD[J]. Metabolism, 2021, 115: 154433. DOI: 10.1016/j.metabol.2020.154433. [16] DENG Y, ZHAO Q, GONG R. Association between metabolic associated fatty liver disease and chronic kidney disease: A cross-sectional study from NHANES 2017-2018[J]. Diabetes Metab Syndr Obes, 2021, 14: 1751-1761. DOI: 10.2147/DMSO.S292926. [17] TARGHER G, COREY KE, BYRNE CD, et al. The complex link between NAFLD and type 2 diabetes mellitus-mechanisms and treatments[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(9): 599-612. DOI: 10.1038/s41575-021-00448-y. [18] WANG F. The correlation between metabolic syndrome and chronic kidney disease in patients with type 2 diabetes mellitus[J]. Anhui Med Pharm J, 2021, 25(3): 508-511. DOI: 10.3969/j.issn.1009-6469.2021.03.019.王芬. 代谢综合征与2型糖尿病病人慢性肾脏病的相关性分析[J]. 安徽医药, 2021, 25(3): 508-511. DOI: 10.3969/j.issn.1009-6469.2021.03.019. [19] GEHRKE N, SCHATTENBERG JM. Metabolic inflammation-A role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease?[J]. Gastroenterology, 2020, 158(7): 1929-1947. DOI: 10.1053/j.gastro.2020.02.020. [20] SCHUSTER S, CABRERA D, ARRESE M, et al. Triggering and resolution of inflammation in NASH[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(6): 349-364. DOI: 10.1038/s41575-018-0009-6. [21] 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. [22] XU ZH, ZHOU GY, NI XW. A study on the research progress of nutrition management in patients with chronic kidney disease[J]. J Changchun Univ Chin Med, 2021, 37(6): 1422-1424. DOI: 10.13463/j.cnki.cczyy.2021.06.064.徐志华, 周广宇, 倪晓威. 慢性肾脏病患者营养管理的研究进展[J]. 长春中医药大学学报, 2021, 37(6): 1422-1424. DOI: 10.13463/j.cnki.cczyy.2021.06.064. [23] HELSLEY RN, MOREAU F, GUPTA MK, et al. Tissue-specific fructose metabolism in obesity and diabetes[J]. Curr Diab Rep, 2020, 20(11): 64. DOI: 10.1007/s11892-020-01342-8. [24] FEDERICO A, ROSATO V, MASARONE M, et al. The role of fructose in non-alcoholic steatohepatitis: old relationship and new insights[J]. Nutrients, 2021, 13(4): 1314. DOI: 10.3390/nu13041314. [25] SANCHEZ-LOZADA LG, ANDRES-HERNANDO A, GARCIA-ARROYO FE, et al. Uric acid activates aldose reductase and the polyol pathway for endogenous fructose and fat production causing development of fatty liver in rats[J]. J Biol Chem, 2019, 294(11): 4272-4281. DOI: 10.1074/jbc.RA118.006158. [26] CUI Y, LIU J, SHI H, et al. Serum uric acid is positively associated with the prevalence of nonalcoholic fatty liver in non-obese type 2 diabetes patients in a Chinese population[J]. J Diabetes Complications, 2021, 35(5): 107874. DOI: 10.1016/j.jdiacomp.2021.107874. [27] FERNÁNDEZ RODRÍGUEZ CM, ALLER R, GUTIÉRREZ GARCÍA ML, et al. Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD)[J]. Rev Esp Enferm Dig, 2019, 111(4): 264-269. DOI: 10.17235/reed.2019.5965/2018. [28] KAWACHI Y, FUJISHIMA Y, NISHIZAWA H, et al. Increased plasma XOR activity induced by NAFLD/NASH and its possible involvement in vascular neointimal proliferation[J]. JCI Insight, 2021, 6(17): e144762. DOI: 10.1172/jci.insight.144762. [29] ZHANG J, XU C, ZHAO Y, et al. The significance of serum xanthine oxidoreductase in patients with nonalcoholic fatty liver disease[J]. Clin Lab, 2014, 60(8): 1301-1307. DOI: 10.7754/clin.lab.2013.130516. [30] SHARAF EL DIN U, SALEM MM, ABDULAZIM DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review[J]. J Adv Res, 2017, 8(5): 537-548. DOI: 10.1016/j.jare.2016.11.004. [31] YANAI H, ADACHI H, HAKOSHIMA M, et al. Molecular biological and clinical understanding of the pathophysiology and treatments of hyperuricemia and its association with metabolic syndrome, cardiovascular diseases and chronic kidney disease[J]. Int J Mol Sci, 2021, 22(17): 9221. DOI: 10.3390/ijms22179221. [32] CAO X, WU L, CHEN Z. The association between elevated serum uric acid level and an increased risk of renal function decline in a health checkup cohort in China[J]. Int Urol Nephrol, 2018, 50(3): 517-525. DOI: 10.1007/s11255-017-1732-6. [33] LIU X, ZHAI T, MA R, et al. Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis[J]. Ren Fail, 2018, 40(1): 289-297. DOI: 10.1080/0886022X.2018.1456463. [34] HU H, LIN A, KONG M, et al. Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives[J]. J Gastroenterol, 2020, 55(2): 142-158. DOI: 10.1007/s00535-019-01649-8. [35] SAFARI Z, GÉRARD P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)[J]. Cell Mol Life Sci, 2019, 76(8): 1541-1558. DOI: 10.1007/s00018-019-03011-w. [36] JIANG S, SHUI Y, CUI Y, et al. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin Ⅱ-induced hypertension[J]. Redox Biol, 2021, 46: 102115. DOI: 10.1016/j.redox.2021.102115. [37] ZENG Y, GUO M, FANG X, et al. Gut microbiota-derived trimethylamine N-oxide and kidney function: a systematic review and meta-analysis[J]. Adv Nutr, 2021, 12(4): 1286-1304. DOI: 10.1093/advances/nmab010. [38] LI YJ, CHEN X, KWAN TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid-mediated activation of G protein-coupled receptors GPR43 and GPR109A[J]. J Am Soc Nephrol, 2020, 31(6): 1267-1281. DOI: 10.1681/ASN.2019101029. [39] SALGUERO MV, AL-OBAIDE M, SINGH R, et al. Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease[J]. Exp Ther Med, 2019, 18(5): 3461-3469. DOI: 10.3892/etm.2019.7943. [40] WANG X, YANG S, LI S, et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents[J]. Gut, 2020, 69(12): 2131-2142. DOI: 10.1136/gutjnl-2019-319766. [41] ARROYAVE-OSPINA JC, WU Z, GENG Y, et al. Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: implications for prevention and therapy[J]. Antioxidants (Basel), 2021, 10(2): 174. DOI: 10.3390/antiox10020174. [42] BRAGA PC, ALVES MG, RODRIGUES AS, et al. Mitochondrial pathophysiology on chronic kidney disease[J]. Int J Mol Sci, 2022, 23(3): 1776. DOI: 10.3390/ijms23031776. [43] PAES A, GASPAR RS, FUENTES E, et al. Lipid metabolism and signaling in platelet function[J]. Adv Exp Med Biol, 2019, 1127: 97-115. DOI: 10.1007/978-3-030-11488-6_7. [44] TSUCHIDA T, FRIEDMAN SL. Mechanisms of hepatic stellate cell activation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397-411. DOI: 10.1038/nrgastro.2017.38. [45] KABRA H, WALIMBE T, STUART K, et al. Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis[J]. Biomaterials, 2021, 269: 120538. DOI: 10.1016/j.biomaterials.2020.120538. [46] YANG K, DU C, WANG X, et al. Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice[J]. Blood, 2017, 129(19): 2667-2679. DOI: 10.1182/blood-2016-10-744060. [47] DEL CAMPO JA, GALLEGO-DURÁN R, GALLEGO P, et al. Genetic and epigenetic regulation in nonalcoholic fatty liver disease (NAFLD)[J]. Int J Mol Sci, 2018, 19(3): 911. DOI: 10.3390/ijms19030911. [48] ZHANG X, DENG F, ZHANG Y, et al. PPARγ attenuates hepatic inflammation and oxidative stress of non-alcoholic steatohepatitis via modulating the miR-21-5p/SFRP5 pathway[J]. Mol Med Rep, 2021, 24(5): 823. DOI: 10.3892/mmr.2021.12463. [49] LOBODA A, SOBCZAK M, JOZKOWICZ A, et al. TGF-β1/Smads and miR-21 in renal fibrosis and inflammation[J]. Mediators Inflamm, 2016, 2016: 8319283. DOI: 10.1155/2016/8319283. [50] PAIK J, GOLABI P, YOUNOSZAI Z, et al. Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease[J]. Liver Int, 2019, 39(2): 342-352. DOI: 10.1111/liv.13992. [51] WIJARNPREECHA K, THONGPRAYOON C, SCRIBANI M, et al. Noninvasive fibrosis markers and chronic kidney disease among adults with nonalcoholic fatty liver in USA[J]. Eur J Gastroenterol Hepatol, 2018, 30(4): 404-410. DOI: 10.1097/MEG.0000000000001045. [52] SAITO H, TANABE H, KUDO A, et al. High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes[J]. Sci Rep, 2021, 11(1): 11753. DOI: 10.1038/s41598-021-88285-6. [53] WU L, ZHANG M, HU H, et al. Elevated gamma-glutamyl transferase has a non-linear association with incident non-alcoholic fatty liver disease in the non-obese Chinese population: a secondary retrospective study[J]. Lipids Health Dis, 2021, 20(1): 142. DOI: 10.1186/s12944-021-01577-8. [54] SHEN ZW, XING J, WANG QL, et al. Association between serum γ-glutamyltransferase and chronic kidney disease in urban Han Chinese: a prospective cohort study[J]. Int Urol Nephrol, 2017, 49(2): 303-312. DOI: 10.1007/s11255-016-1429-2. [55] FAN Y, JIN X, MAN C, et al. Association of serum gamma-glutamyltransferase with chronic kidney disease risk: a meta-analysis[J]. Free Radic Res, 2018, 52(8): 819-825. DOI: 10.1080/10715762.2018.1492120. [56] OCHIAI H, SHIRASAWA T, YOSHIMOTO T, et al. Elevated alanine aminotransferase and low aspartate aminotransferase/alanine aminotransferase ratio are associated with chronic kidney disease among middle-aged women: a cross-sectional study[J]. BMC Nephrol, 2020, 21(1): 471. DOI: 10.1186/s12882-020-02144-6. [57] SHAO CP, XU YQ. Association of serum uric acid-to-creatinine ratio with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2021, 37(10): 2348-2351. DOI: 10.3969/j.issn.1001-5256.2021.10.018.邵翠萍, 徐有青. 血清尿酸/肌酐比值与非酒精性脂肪性肝病的相关性分析[J]. 临床肝胆病杂志, 2021, 37(10): 2348-2351. DOI: 10.3969/j.issn.1001-5256.2021.10.018. [58] SUN Y, LIU Y, WANG FF. The relationship between serum uric acid/creatinine and early diabetic nephropathy in patients with type 2 diabetes mellitus[J]. Chin J Health Lab Technol, 2021, 31(13): 1600-1602, 1606. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202113018.htm孙悦, 刘燕, 王菲菲. 血清尿酸/肌酐比值与早期糖尿病肾病的相关性探讨[J]. 中国卫生检验杂志, 2021, 31(13): 1600-1602, 1606. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202113018.htm [59] WONG VW, WONG GL, CHAN RS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease[J]. J Hepatol, 2018, 69(6): 1349-1356. DOI: 10.1016/j.jhep.2018.08.011. [60] CHALASANI N, YOUNOSSI Z, LAVINE JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2018, 67(1): 328-357. DOI: 10.1002/hep.29367. [61] European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease[J]. J Hepatol, 2016, 64(6): 1388-1402. DOI: 10.1016/j.jhep.2015.11.004. [62] Chinese Society of Endocrinology, Chinese Diabetes Society. Management of Chinese adults with type 2 diabetes and non-alcoholic fatty liver disease: an expert consensus[J]. Chin J Endocrinol Metab, 2021, 37(7): 589-598. DOI: 10.3760/cma.j.cn311282-20210105-00016.中华医学会内分泌学分会, 中华医学会糖尿病学分会. 中国成人2型糖尿病合并非酒精性脂肪性肝病管理专家共识[J]. 中华内分泌代谢杂志, 2021, 37(7): 589-598. DOI: 10.3760/cma.j.cn311282-20210105-00016. [63] MUSSO G, CASSADER M, COHNEY S, et al. Fatty liver and chronic kidney disease: novel mechanistic insights and therapeutic opportunities[J]. Diabetes Care, 2016, 39(10): 1830-1845. DOI: 10.2337/dc15-1182.
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