Division of Nephrology and Hypertension, Department of Internal Medicine, Atsugi City Hospital, 1-16-36, Mizuhiki, Atsugi City, Kanagawa, 243-8588, Japan.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
BMC Nephrol. 2024 May 20;25(1):171. doi: 10.1186/s12882-024-03612-z.
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.
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.
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.
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。未经适当治疗，LPG 引起的慢性肾脏病（CKD）进展，大约一半的患者在疾病发病后 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（CVD）的临床过程。在此，我们报告首例使用动脉僵硬度评估 LPG 患者 CVD 风险的病例。
一名 32 岁的日本男性因持续性蛋白尿被转诊至我院。肾脏活检显示毛细血管腔明显扩张，腔内充满淡染血栓，油红 O 染色阳性。电镜下可见毛细血管腔内血栓呈低电子密度，部分血栓内有空泡。甲苯胺蓝和苏丹 IV 染色用于电子显微镜观察 Epon 包埋组织样本的薄切片。在毛细血管腔、血管壁和肾小管细胞质中观察到苏丹 IV 阳性液滴。观察到血清 ApoE 浓度升高。激光微切割肾小球石蜡切片的液相色谱-串联质谱显示 ApoE 增加。ApoE 的直接脱氧核糖核酸测序显示 ApoE Sendai 突变（Arg145Pro）杂合性。最终该患者被诊断为 ApoE-Sendai 突变（Arg145Pro）杂合的 LPG。值得注意的是，在诊断时，他的动脉僵硬度明显高于其年龄。动脉僵硬度通过肱踝脉搏波速度（baPWV）进行测量，相当于 56 岁男性的水平。接受非诺贝特和氯沙坦治疗 3 个月后，蛋白尿显著减少，baPWV 改善。此外，尽管血清 ApoE 水平没有下降，但这些效果仍得以维持。
在此，我们报告了一例 LPG 患者在诊断时动脉僵硬度明显增加的病例，非诺贝特和氯沙坦联合治疗成功改善了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 LPG 患者 CVD 风险的病例报告。
