恶性高血压肾硬化的临床病理特征及预后分析

doi:10.3969/j.issn.1006-7795.2024.05.014

摘要/Abstract

摘要： 目的探究原发性恶性高血压肾硬化（malignant hypertensive nephrosclerosis，MHTN）患者的临床病理及预后特征，明确影响MHTN患者预后的关键因素。方法收集2012年12月至2023年6月空军军医大学西京医院经肾活体组织检查确诊的高血压肾病患者的病理及临床资料，根据病理结果区分MHTN和良性肾动脉硬化（benign arteriolosclerosis nephrosclerosis，BAN）。采用单因素和多因素Cox回归分析确定影响MHTN患者肾脏预后的危险因素，通过Kaplan-Meier生存曲线计算肾脏累积生存率。研究终点定义为终末期肾病或死亡的复合终点。结果共计231例原发性高血压肾病患者纳入研究，其中MHTN患者75例，中位随访时间为20.8（13.2，47.1）个月，共36例（52.0%）达到肾脏复合终点。与BAN患者相比，MHTN患者平均年龄更小、临床表现更重、预后更差。单因素Cox分析显示，估算肾小球滤过率（estimated glomerular filtration rate，eGFR）、尿微量白蛋白肌酐比、N-乙酰-β-D氨基葡萄糖苷酶、血浆白蛋白、血清钙、胱抑素C（cystatin C，Cys-C）、血红蛋白（hemoglobin，Hb）、纤维蛋白原（fibrinogen，FIB）和肾脏总体慢性病理评分（Total Renal Chronic Pathological Score，TRCS）与MHTN患者肾脏复合终点的发生风险增加相关。校正病理评分后的多因素Cox分析显示，Cys-C（HR=1.490，95% CI: 1.144~1.942，P=0.003）、Hb（HR=0.981，95% CI: 0.963~0.999，P=0.042）、FIB（HR=1.650，95% CI: 1.125~2.419，P=0.010）、TRCS（HR=1.317，95% CI: 1.057~1.640，P=0.014）是影响MHTN患者肾脏预后的独立危险因素。结论在MHTN患者中，Cys-C、FIB升高、Hb降低和更严重的肾脏病理改变预示着不良肾脏结局。进一步提升临床诊疗过程中MHTN患者的肾活体组织检查率更有助于评估患者预后。

关键词: 恶性高血压肾硬化, 良性肾动脉硬化, 慢性肾脏病, 危险因素, 肾脏预后

Abstract: Objective To explore the clinicopathological and prognostic characteristics of patients with primary malignant hypertensive nephrosclerosis (MHTN) and identify the key factors influencing the prognosis of MHTN patients. Methods The pathological and clinical data of hypertensive nephropathy patients diagnosed by renal biopsy in Xijing Hospital of Air Force Medical University from December 2012 to June 2023, were collected. Patients were distinguished into MHTN and benign arteriolosclerosis nephrosclerosis (BAN) groups based on pathological results. Univariate and multivariate Cox regression analyses were performed to identify the risk factors affecting renal prognosis in MHTN patients. Kaplan-Meier survival curves were used to calculate renal cumulative survival rates. The study endpoint was defined as a composite endpoint of end-stage renal disease or death. Results A total of 231 patients with primary hypertensive nephropathy were included in the study, of which 75 were MHTN patients. The median follow-up time was 20.8 (13.2, 47.1) months, and 36 (52.0%) patients reached the renal composite endpoint. Compared with BAN patients, MHTN patients had more severe clinical manifestations, worse prognosis, and younger average age. Univariate Cox analysis showed that estimated glomerular filtration rate (eGFR), urinary microalbumin creatinine ratio, urinary N-acetyl-β-D-glucosaminidase, plasma albumin, serum calcium, cystatin C (Cys-C), hemoglobin (Hb), fibrinogen (FIB), and total renal chronic pathological score (TRCS) were associated with an increased risk of renal composite endpoints in MHTN patients. Multivariate Cox regression after adjusting for pathological scores revealed that Cys-C (HR=1.490, 95% CI: 1.144-1.942, P=0.003), Hb (HR=0.981, 95% CI: 0.963-0.999, P=0.042), FIB (HR=1.650, 95% CI: 1.125-2.419, P=0.010), and TRCS (HR=1.317, 95% CI: 1.057-1.640, P=0.014) were independent risk factors for renal prognosis in MHTN patients. Conclusions In MHTN patients, elevated Cys-C and FIB levels, decreased Hb, and severe pathological changes predict adverse renal outcomes. Further increasing the rate of renal biopsy in MHTN patients during clinical diagnosis and treatment can help assess their prognosis.

Key words: alignant hypertensive nephrosclerosis, benign renal arteriosclerosis, chronic kidney disease, risk factors, prognosis of kidney

中图分类号:

秦云龙, 周瑾, 刘萌, 罗开发, 王安静, 王頔, 赵晋, 孙世仁. 恶性高血压肾硬化的临床病理特征及预后分析[J]. 首都医科大学学报, 2024, 45(5): 838-845.

Qin Yunlong, Zhou Jin, Liu Meng, Luo Kaifa, Wang Anjing, Wang Di, Zhao Jin, Sun Shiren. Analysis of clinicopathological characteristics and prognosis of malignant hypertensive nephrosclerosis[J]. Journal of Capital Medical University, 2024, 45(5): 838-845.

参考文献

［1］Boulestreau R, S′piewak M, Januszewicz A, et al. Malignant hypertension: a systemic cardiovascular disease: JACC review topic of the week［J］. J Am Coll Cardiol, 2024, 83(17): 1688－1701.
［2］Boulestreau R, van den Born B H, Lip G Y H, et al. Malignant hypertension: current perspectives and challenges［J］. J Am Heart Assoc, 2022, 11(7): e023397.
［3］王海燕, 赵明辉. 肾脏病学［M］. 4版. 北京: 人民卫生出版社, 2020.
［4］Leiba A, Fishman B, Twig G, et al. Association of adolescent hypertension with future end-stage renal disease［J］. JAMA Intern Med, 2019, 179(4): 517－523.
［5］Carriazo S, Vanessa Perez-Gomez M, Ortiz A. Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology［J］. Clin Kidney J, 2020, 13(4): 504－509.
［6］潘涛, 张文生, 马路, 等. 恶性高血压肾损害的临床及病理分析［J］. 中国中西医结合肾病杂志, 2014, 15(7): 597－599.
［7］高血压肾病诊治中国专家共识组成员. 高血压肾病诊断和治疗中国专家共识(2022)［J］. 中华高血压杂志, 2022, 30(4): 307－317.
［8］Heaf J G, Hansen A, Laier G H. Hypertensive nephropathy is associated with an increased risk of myeloma, skin, and renal cancer［J］. J Clin Hypertens (Greenwich), 2019, 21(6): 786－791.
［9］Jia Q, Ma F, Zhao J, et al. Effect of corticosteroids combined with cyclophosphamide or mycophenolate mofetil therapy for IgA nephropathy with stage 3 or 4 chronic kidney disease: a retrospective cohort study［J］. Front Pharmacol, 2022, 13: 946165.
［10］Sethi S, D'Agati V D, Nast C C, et al. A proposal for standardized grading of chronic changes in native kidney biopsy specimens［J］. Kidney Int, 2017, 91(4): 787－789.
［11］Qin Y L, Yu Z X, Wu H, et al. Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy［J］. Heliyon, 2024, 10(1): e23436.
［12］陶陈洋. 恶性高血压肾损害的临床病理特点及影响因素分析［D］. 郑州: 郑州大学, 2019.
［13］Zhuang Y, Ding C Y, Xu Y J, et al. Association between long-term pulse pressure trajectories and risk of end-stage renal diseases in incident malignant hypertensive nephropathy: a cohort study［J］. Blood Press Monit, 2021, 26(1): 14－21.
［14］Beck G J, Berg R L, Coggins C H, et al. Design and statistical issues of the modification of diet in renal disease trial. The modification of diet in renal disease study group［J］. Control Clin Trials, 1991, 12(5): 566－586.
［15］Wright J T Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial［J］. JAMA, 2002, 288(19): 2421－2431.
［16］Ruggenenti P, Perna A, Loriga G, et al. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial［J］. Lancet, 2005, 365(9463): 939－946.
［17］Boulestreau R, S′piewak M, Januszewicz A, et al. Malignant hypertension: a systemic cardiovascular disease: JACC review topic of the week［J］. J Am Coll Cardiol, 2024, 83(17): 1688－1701.
［18］Pavlakou P, Gakiopoulou H, Djudjaj S, et al. Keratin expression in podocytopathies, ANCA-associated vasculitis and IgA nephropathy［J］. Int J Mol Sci, 2024, 25(3): 1805.
［19］Bobart S A, Han H, Tehranian S, et al. Noninvasive diagnosis of PLA2R-associated membranous nephropathy: a validation study［J］. Clin J Am Soc Nephrol, 2021, 16(12): 1833－1839.
［20］Zhang X D, Luo F, Chen R X, et al. Use of histologic parameters to predict glomerular disease progression: findings from the China kidney biopsy cohort study［J］. Am J Kidney Dis, 2023, 81(4): 416－424.e1.
［21］Liang S S, Le W B, Liang D D, et al. Clinico-pathological characteristics and outcomes of patients with biopsy-proven hypertensive nephrosclerosis: a retrospective cohort study［J］. BMC Nephrol, 2016, 17: 42.
［22］Wolberg A S. Fibrinogen and fibrin: synthesis, structure, and function in health and disease［J］. J Thromb Haemost, 2023, 21(11): 3005－3015.
［23］Luyendyk J P, Schoenecker J G, Flick M J. The multifaceted role of fibrinogen in tissue injury and inflammation［J］. Blood, 2019, 133(6): 511－520.
［24］Surma S, Banach M. Fibrinogen and atherosclerotic cardiovascular diseases-review of the literature and clinical studies［J］. Int J Mol Sci, 2021, 23(1): 193.
［25］Wang J, Zhang Y L, Li K X, et al. Retrospective study of aging and sex-specific risk factors of COVID-19 with hypertension in China［J］. Cardiovasc Ther, 2022, 2022: 5978314.
［26］Wang X, Pan Y, Zhang R, et al. Inflammation and adverse outcomes in patients with acute ischemic stroke with and without chronic kidney disease［J］.J Am Heart Assoc, 2024, 13(9): e033450.
［27］Li J, Wang Z, Zhang B X, et al. Predictive value of combining the level of fibrinogen and CHA2DS2-VASC score for contrast-induced acute kidney injury in patients with acute coronary syndromes undergoing percutaneous coronary intervention［J］. Int Urol Nephrol, 2022, 54(9): 2385－2392.
［28］Stack A G, Donigiewicz U, Abdalla A A, et al. Plasma fibrinogen associates independently with total and cardiovascular mortality among subjects with normal and reduced kidney function in the general population［J］. QJM, 2014, 107(9): 701－713.
［29］Benoit S W, Ciccia E A, Devarajan P. Cystatin C as a biomarker of chronic kidney disease: latest developments［J］. Expert Rev Mol Diagn, 2020, 20(10): 1019－1026.
［30］Keller T, Messow C M, Lubos E, et al. Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study［J］. Eur Heart J, 2009, 30(3): 314－320.
［31］Omaygenç M O, Özcan Ö U, çakal B, et al. Cystatin C and uncontrolled hypertension［J］. Anatol J Cardiol, 2020, 24(5): 309－315.
［32］Zhao M, Che Q, Zhang Y, et al. Expression and clinical significance of serum cystatin C in patients with hypertension and coronary heart disease［J］. Medicine (Baltimore), 2020, 99(22): e20029.
［33］杨茹, 李保林, 梁微微, 等. BNP、CRP、CysC等指标对心肌梗死患者预后不良的预测价值及列线图预测模型构建［J］. 国际检验医学杂志, 2024, 45(6): 757－761.
［34］Yang X, Fan J, Wu Y Z, et al. The value of electrophoresis and chemical detection in the diagnosis of hypertensive nephropathy［J］. Int J Gen Med, 2021, 14: 4803－4808.

[1]	张大坤, 张洪波, 董德鑫, 高翔, 郑瀚, 张浪. 上尿路结石行输尿管镜碎石术后尿源性脓毒血症的早期诊治[J]. 首都医科大学学报, 2024, 45(5): 870-874.
[2]	封怡多, 黄琪, 周亦伦 . 慢性肾脏病患者认知功能状况及危险因素[J]. 首都医科大学学报, 2023, 44(5): 788-794.