黄小杏,古贤君,郭帅魁

在肾小球疾病中，核心的临床表现就是肾病综合征(nephrotic syndrome,NS)，其会导致肾小球过滤屏障的渗透率出现异变，从而引发一系列病理生理变化。NS中常见的一种并发症状就是脂质代谢混乱，它不但能促进肾脏疾病的发展，加快肾功能衰退，还增加动脉粥样硬化和心脏疾病的发病机率，对患者的远期健康状况造成重大威胁。本文整理NS伴随脂质代谢紊乱的常见表现与核心特点，解读肝脏脂蛋白合成与清除失衡、脂酶活性异常、受体介导的代谢受阻等基础机制，重点介绍血管生成素样蛋白家族调控、前蛋白转化酶枯草溶菌素9介导的肝肾相互作用、炎症与脂质紊乱的关联以及肠道菌群的调节作用等最新研究进展，同时对靶向干预方案与未来研究方向做出展望，为肾病综合征脂质代谢紊乱的基础探索与临床应用提供理论参考。

肾病综合征；脂质代谢紊乱；血管生成素样蛋白；前蛋白转化酶枯草溶菌素9；肠道菌群

[1] Zabala Ramirez M J,Stein E J,Jain K.Nephrotic syndrome for the internist[J].Medical Clinics of North America,2023,107(4):727-737. [2] Untersulzner C,Gauckler P,Matyjek A,et al.Cardiovascular disease and risk management in patients with nephrotic syndrome[J].Kidney Research and Clinical Practice,2025. [3] Agrawal S,Zaritsky J J,Fornoni A,et al.Dyslipidaemia in nephrotic syndrome:mechanisms and treatment[J].Nature Reviews.Nephrology, 2018,14(1):57-70. [4] Lent-Schochet D,Jialal I.Biochemistry,lipoprotein metabolism[M]//StatPearls[internet].StatPearls Publishing,2023. [5] Jiang Q,Feng B,Zhao Y,et al.Proatherogenic changes in the quantity and quality of lipoproteins in adults with idiopathic nephrotic syndrome[J].Clinica Chimica Acta,2025,570:120206. [6] Simachew Y M,AntonićT,GojkovićT,et al.Lipoproteins and cholesterol homeostasis in paediatric nephrotic syndrome patients[J]. Biochemia Medica,2022,32(2):20706. [7] Vaziri N D.Disorders of lipid metabolism in nephrotic syndrome:mechanisms and consequences[J].Kidney International,2016,90(1):41-52. [8] Vaziri N D,Liang K,Parks J S.Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome[J].American Journal of Physiology Renal Physiology,2001,280(5):F823-F828. [9] Vaziri N D.HDL abnormalities in nephrotic syndrome and chronic kidney disease[J].Nature Reviews Nephrology,2016,12(1):37-47. [10] Zhao Y,Marcel Y L.Serum albumin is a significant intermediate in cholesterol transfer between cells and lipoproteins[J].Biochemistry, 1996,35(22):7174-7180. [11] Moulin P,Appel G,Ginsberg H,et al.Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome:role in dyslipidemia[J].Journal of Lipid Research,1992,33(12):1817-1822. [12] Vaziri N D,Liang K.Up-regulation of acyl-coenzyme A:cholesterol acyltransferase(ACAT)in nephrotic syndrome[J].Kidney International,2002,61(5):1769-1775. [13] Wu S A,Kersten S,Qi L.Lipoprotein lipase and its regulators:an unfolding story[J].Trends in Endocrinology and Metabolism: TEM,2021,32(1):48-61. [14] Alvi S S,Ansari I A,Ahmad M K,et al.Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and apo-CIII mediated lipoprotein lipase activity[J].Biomedicine&Pharmacotherapy,2017,96:1082-1093. [15] Vaziri N D,Gollapudi P,Han S,et al.Nephrotic syndrome causes upregulation of HDL endocytic receptor and PDZK-1-dependent downregulation of HDL docking receptor[J].Nephrology,Dialysis,Transplantation,2011,26(10):3118-3123. [16] Vaziri N D.Role of dyslipidemia in impairment of energy metabolism,oxidative stress,inflammation and cardiovascular disease in chronic kidney disease[J].Clinical and Experimental Nephrology,2014,18(2):265-268. [17] Haas M E,Levenson A E,Sun X,et al.The role of proprotein convertase subtilisin/kexin type 9 in nephrotic syndrome-associated hypercholesterolemia[J].Circulation,2016,134(1):61-72. [18] Weng S,Ding C,Lin J,et al.ANGPTL3 and residual atherosclerotic risk:from lipid metabolism to therapeutic targeting[J].Frontiers in endocrinology,2025,16:1706091. [19] Zhong F,Liu S,Li Y,et al.ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome[J].Lipids in Health and Disease,2022,21:38. [20] Tamehri Zadeh S S,Toth P P,Shapiro M D,et al.ANGPTL3 vital role in different kidney diseases.Current knowledge and future perspectives[J].Biomedicine&Pharmacotherapy,2025,188:118189. [21] Watts G F,Scott R,Sullivan D,et al.Zodasiran for cholesterol and triglyceride lowering in patients with hyperlipidemia:final report of phase 1 basket trial[J].Nature Medicine,2026,32(4):1432-1443. [22] Chi X,Britt E C,Shows H W,et al.ANGPTL8 promotes the ability of ANGPTL3 to bind and inhibit lipoprotein lipase[J].Molecular Metabolism,2017,6(10):1137-1149. [23] Li Y,Liu Q,Kang C,et al.Serum and urine ANGPTL8 expression levels are associated with hyperlipidemia and proteinuria in primary nephrotic syndrome[J].BMC Nephrology,2021,22(1):131-136. [24] Wei X,Zhu Y,Du J,et al.Analysis of ANGPTL8 promoter activity and screening of related transcription factors in bovine[J].Gene, 2021,784:145594. [25] Wen Y,Chen Y Q,Konrad R J.Angiopoietin-like protein 8:a multifaceted protein instrumental in regulating triglyceride metabolism[J]. Current Opinion in Lipidology,2024,35(2):58-65. [26] Clement L C,MacéC,Avila-Casado C,et al.Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome[J].Nature Medicine,2014,20(1):37-46. [27] Li Y,Zhang Y,Cao M,et al.Angiopoietin-like protein 4 dysregulation in kidney diseases:a promising biomarker and therapeutic target[J].Frontiers in Pharmacology,2025,15:1475198. [28] Chugh S S,Clement L C.“Idiopathic”minimal change nephrotic syndrome:a podocyte mystery nears the end[J].American Journal of Physiology Renal Physiology,2023,325(6):F685-F694. [29] Zhang G,Li Q.Inflammation induces lipid deposition in kidneys by downregulating renal PCSK9 in mice with adriamycin-induced nephropathy[J].Medical Science Monitor :International Medical Journal of Experimental and Clinical Research,2019,25:5327-5335. [30] Artunc F.Kidney-derived PCSK9—a new driver of hyperlipidemia in nephrotic syndrome?[J].Kidney International,2020, 98(6):1393-1395. [31] Zhang Y,Ramirez V.Effective treatment of statin-and ezetimibe-resistant hyperlipidemia in a patient with active membranous nephrotic syndrome using a PCSK9 inhibitor[J].Journal of Clinical Lipidology,2025,19(3):e29. [32] Skeby C K,Hummelgaard S,Gustafsen C,et al.Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome[J].Kidney International,2023,104(4):754-768. [33] Landmesser U,Ray K K,Raal F J,et al.Inclisiran in patients with CKD:post hoc pooled analysis of three phase 3 trials[J].Journal of the American Society of Nephrology,2026:1-10. [34] Zhang G,Li Q,Wang L,et al.The effects of inflammation on lipid accumulation in the kidneys of children with primary nephrotic syndrome[J].Inflammation,2011,34(6):645-652. [35] 赵诚尚,彭鑫平,李济廷,等.脂质代谢在慢性肾脏病进展中的关键作用及研究进展[J].临床医学进展,2025(11):2158-2167. [36] Zhang Y,Sun C,Wang Y,et al.Targeting gut–liver–kidney axis:microbiota-derived metabolites and therapeutic implications[J].Cell Communication and Signaling :CCS,2026,24:107.

点击下载PDF