关键词: Apolipoprotein E Arterial stiffness CAVI Fibrate Lipoprotein glomerulopathy Oil Red O PWV Sudan IV Triglyceride

Mesh : Humans Male Adult Losartan / therapeutic use Vascular Stiffness / drug effects Fenofibrate / therapeutic use Drug Therapy, Combination Hypolipidemic Agents / therapeutic use Kidney Diseases / drug therapy Apolipoproteins E / genetics

来  源:   DOI:10.1186/s12882-024-03612-z   PDF(Pubmed)

Abstract:
BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.
METHODS: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.
CONCLUSIONS: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.
摘要:
背景:脂蛋白肾小球病(LPG)是一种载脂蛋白E(ApoE)相关的肾小球疾病,与III型高脂血症有关。如果没有适当的治疗,由LPG引起的慢性肾脏疾病(CKD)进展,大约一半的患者在发病后1-27年内发展为终末期肾病。然而,很少有研究强调LPG患者心血管疾病(CVDs)的临床过程。在这里,我们报告了首例LPG患者,使用动脉僵硬度评估CVD风险.
方法:一名32岁的日本男子因持续性蛋白尿被转诊至我院。肾活检显示毛细血管腔明显扩张,含有浅色血栓,用油红O染色呈阳性。电子显微镜显示毛细血管腔中存在血栓,部分血栓中电子密度低,液泡大小各异。使用甲苯胺蓝和苏丹IV染色剂对Epon包埋的组织样品的薄切片进行染色以进行电子显微镜检查。在毛细血管腔中观察到苏丹IV阳性液滴,血管壁,和管状细胞的细胞质。观察到血清ApoE浓度增加。从石蜡切片中进行激光显微解剖的肾小球的液相色谱-串联质谱显示ApoE增加。ApoE的直接脱氧核糖核酸测序显示杂合ApoE仙台突变(Arg145Pro)。患者最终被诊断为具有ApoE-Sendai突变杂合性的LPG(Arg145Pro)。值得注意的是,在诊断时,与他这个年龄相比,他的动脉僵硬度明显增加。使用臂踝脉搏波传导速度(baPWV)测量动脉硬度,相当于一个56岁的男人。非诺贝特和氯沙坦治疗三个月后,随着baPWV的改善,蛋白尿显著减少.此外,尽管血清ApoE水平没有降低,但这些作用得以维持.
结论:此处,我们报告了一名LPG患者在诊断时动脉僵硬度显着增加的病例,非诺贝特和氯沙坦联合治疗可成功改善蛋白尿和动脉僵硬度。据我们所知,这是首例使用动脉僵硬度评估CVD风险的LPG病例报告.
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