低密度脂蛋白胆固醇水平对特发性膜性肾病患者临床和病理的影响

Clinical and Pathological Effects of Low-Density Lipoprotein Cholesterol Levels in Patients with Idiopathic Membranous Nephropathy

摘要: 目的：研究特发性膜性肾病患者不同低密度脂蛋白胆固醇水平对临床、病理特点的影响，探讨低密度脂蛋白胆固醇(LDL-C)升高的相关因素，为临床诊治提供理论依据。方法：回顾性分析2013年1月~2024年3月在青岛大学附属医院经肾脏穿刺病理活检确诊的641例IMN患者，按照低密度脂蛋白胆固醇水平分为低LDL-C组(< 3.4 mmol/L) 182例、中LDL-C组(≥ 3.4且 < 4.1 mmol/L) 101例及高LDL-C组(≥ 4.1 mmol/L) 358例。收集所有患者初次肾脏活检时的临床及病理资料并进行组间比较。运用Logistic回归分析方法，分析特发性膜性肾病患者不同低密度脂蛋白胆固醇水平与临床病理特点的关系。结果：3组患者MN病理分期以I期及II期为主；肾脏PLA2R阳性占比分别为低LDL-C组92.8%、中LDL-C组81.6%、高LDL-C组93.8%；血PLA2R-ab阳性占比分别为低LDL-C组56.4%、中LDL-C组48.1%、高LDL-C组57.1%。高LDL-C组的男性比例、肾病综合征状态、镜下血尿、收缩压、舒张压、血小板计数、24小时尿蛋白定量均高于其他两组；吸烟史、高血压病史、D-二聚体升高、血白蛋白及前白蛋白降低程度、血红蛋白、尿素氮、补体C4水平均高于中LDL-C组(P < 0.05)。高LDL-C组的肾小管间质慢性病变范围、肾小管萎缩程度、IgG4沉积阳性率高于低LDL-C组；IgG沉积阳性、IgG3、IgG4、λ链阳性、肾脏PLA2R阳性高于中LDL-C组；中LDL-C组肾小球基底膜厚度、肾脏PLA2R阳性率低于低LDL-C组(P < 0.05)。Logistic分析结果提示，患者的肾病综合征状态、D-二聚体升高、镜下血尿、血白蛋白降低、补体C4升高是特发性膜性肾病伴低密度脂蛋白胆固醇升高的独立危险因素。结论：IMN伴不同水平LDL-C升高患者的临床及病理表现存在差异，高LDL-C组患者病情较重，如肾功能较差、肾脏病理损伤较重等，且其发生与肾病综合征状态、D-二聚体升高、镜下血尿、血白蛋白、补体C4等有关，低密度脂蛋白胆固醇水平并非肝脏对MN低蛋白血症的被动反应，临床上应关注特发性膜性肾病中升高患者的肾功能进展。

Abstract: Objective: To investigate the impact of varying low-density lipoprotein cholesterol (LDL-C) levels on clinical and pathological characteristics in patients with idiopathic membranous nephropathy (IMN), and to identify factors associated with elevated LDL-C, thereby providing a theoretical basis for clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on 641 IMN patients diagnosed by renal biopsy at the Affiliated Hospital of Qingdao University from January 2013 to March 2024. Patients were categorized into three groups based on their LDL-C levels: low LDL-C group (< 3.4 mmol/L, n = 182), medium LDL-C group (≥ 3.4 and < 4.1 mmol/L, n = 101), and high LDL-C group (≥ 4.1 mmol/L, n = 358). Clinical and pathological data collected at initial renal biopsy were compared across groups. Logistic regression analysis was employed to examine the association between LDL-C levels and clinicopathological features in IMN patients. Results: The majority of patients in all three groups exhibited MN pathological stages I and II. The proportion of PLA2R positivity was 92.8%, 81.6%, and 93.8% in the low, medium, and high LDL-C groups, respectively. The positive rates of PLA2R antibodies were 56.4%, 48.1%, and 57.1% in the respective groups. Compared to the other two groups, the high LDL-C group had higher proportions of males, nephrotic syndrome, microscopic hematuria, systolic and diastolic blood pressure, platelet count, and 24-hour urinary protein. Smoking history, hypertension, increased D-dimer, decreased serum albumin and prealbumin, hemoglobin, urea nitrogen, and complement C4 were significantly higher in the medium LDL-C group than in the low LDL-C group (P < 0.05). The extent of chronic tubulointerstitial lesions, degree of renal tubular atrophy, and IgG4 deposition positivity were greater in the high LDL-C group compared to the low LDL-C group. The positive rates of IgG, IgG3, IgG4, λ chain, and renal PLA2R were higher in the medium LDL-C group than in the low LDL-C group. Glomerular basement membrane thickness and renal PLA2R positivity were lower in the medium LDL-C group compared to the low LDL-C group (P < 0.05). Logistic regression analysis revealed that nephrotic syndrome, elevated D-dimer, microscopic hematuria, decreased serum albumin, and elevated complement C4 were independent risk factors for elevated LDL-C in IMN patients. Conclusion: IMN patients with different LDL-C levels exhibit distinct clinical and pathological manifestations. Those in the high LDL-C group tend to have more severe conditions, including poorer renal function and more pronounced renal pathological damage. These findings suggest that LDL-C elevation is not merely a passive response to liver hypoproteinemia in MN, and clinicians should closely monitor renal function progression in IMN patients.