慢性粒细胞性白血病合并膜增生性肾小球肾炎1例并文献复习

doi:10.3969/j.issn.1004-583X.2026.03.011

摘要/Abstract

摘要：

目的探究慢性粒细胞性白血病患者出现肾病综合征的病因及其鉴别诊断方法。方法回顾性分析1例慢性粒细胞性白血病合并膜增生性肾小球肾炎患者的临床资料, 并复习相关文献。结果患者男性,75岁,主因发现慢性粒细胞性白血病6年,双下肢水肿4年,血清肌酐升高2周入院。入院后完善相关检查,肾功能:血清肌酐150.4 μmol/L,24 h尿蛋白定量1.35 g/24 h,经皮肾穿刺活检病理检查示膜增生性肾小球肾炎伴高血压肾损害。在将甲磺酸伊马替尼减量并结合降压和降尿蛋白等综合治疗后,患者双下肢水肿减轻,尿蛋白明显下降,病情好转。结论当慢性粒细胞性白血病合并肾脏损害时,需详细询问患者的既往病史、用药史,并完善经皮肾穿刺活检病理检查,以鉴别是慢性粒细胞性白血病累及肾脏或是酪氨酸激酶抑制剂相关性肾病。

关键词: 肾小球肾炎, 膜增生性, 白血病, 髓样, 血小板源性生长因子, 酪氨酸激酶抑制剂

Abstract:

Objective To explore the causes of nephrotic syndrome in patients with chronic myeloid leukemia (CML) and methods for differential diagnosis. Methods We retrospectively analyzed the clinical data of one patient with CML complicated by membranoproliferative glomerulonephritis (MPGN) and reviewed the relevant literature. Results The patient was a 75-year-old man with a 6-year history of CML, bilateral lower-limb edema for 4 years, and elevated serum creatinine for 2 weeks prior to admission. On admission, renal function tests showed serum creatinine 150.4 μmol/L and 24-hour urine protein 1.35 g/24 h. Percutaneous renal biopsy demonstrated MPGN with changes consistent with hypertensive renal damage. After reduction of imatinib mesylate dose combined with antihypertensive and antiproteinuric therapy, the patient's lower-limb edema improved and proteinuria decreased markedly; overall clinical condition improved. Conclusion In CML patients who develop renal impairment, a careful review of past medical history and medication exposure is essential, and percutaneous renal biopsy should be performed to distinguish between renal involvement by CML and tyrosine kinase inhibitor-related nephropathy.

Key words: glomerulonephritis, membranoproliferative, leukemia, myeloid, platelet-derived growth factor, tyrosine kinase inhibitors

中图分类号:

R692.31

曹泽贤, 刘宇鑫, 沈士朋, 赵松, 高一平, 刘茂东. 慢性粒细胞性白血病合并膜增生性肾小球肾炎1例并文献复习[J]. 临床荟萃, 2026, 41(3): 259-263.

Cao Zexian, Liu Yuxin, Shen Shipeng, Zhao Song, Gao Yiping, Liu Maodong. Chronic myeloid leukemia complicated by membranoproliferative glomerulonephritis: A case report and literature review[J]. Clinical Focus, 2026, 41(3): 259-263.

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链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.03.011

https://www.lchc.cn/CN/Y2026/V41/I3/259

图/表 2

图1 血清肌酐和24 h尿蛋白定量变化曲线

Fig.1 Changes in serum creatinine and 24-hour urine protein over time

图2 肾脏病理活检 a.肾小球系膜细胞和基质弥漫增生伴插入,双轨征形成(PASM+Masson染色×200);b.肾小球缺血硬化、肾小管上皮灶状萎缩、肾间质灶状纤维化(PASM+Masson染色×100);c.IgM于肾小球毛细血管壁及系膜区花瓣颗粒样沉积(免疫荧光×200);d.肾小球系膜细胞和基质增生,系膜区少量电子致密物沉积广泛插入,上皮细胞足突弥漫性融合,缺血皱缩(电子显微镜)

Fig. 2 Renal histopathology a.Diffuse proliferation of mesangial cells and matrix with mesangial interposition, producing a double-contour (“tram-track”) appearance (PASM + Masson stain, ×200); b.Glomerular ischemic sclerosis, focal tubular epithelial atrophy, and focal interstitial fibrosis (PASM + Masson stain, ×100); c.Granular, petaloid IgM deposits along glomerular capillary walls and in the mesangium (immunofluorescence, ×200); d.Mesangial cell and matrix proliferation with small electron-dense deposits in the mesangial area and extensive mesangial interposition; diffuse effacement of podocyte foot processes and ischemic collapse (electron microscopy)

参考文献 22

[1]	蔡林璇, 陈岷, 童荣生, 等. 伊马替尼用于慢性粒细胞白血病和胃肠道间质瘤的治疗药物监测:国内外相关指南概览[J]. 中国临床药学杂志, 2022, 31(11):874-880.doi:10.19577/j.1007-4406.2022.11.016.
[2]	Ai JY, Liu CF, Zhang W, et al. Current status of drugs targeting PDGF/PDGFR[J]. Drug Discov Today, 2024, 29(7):103989. doi: 10.1016/j.drudis.2024.103989.
[3]	Li D, Huang LT, Zhang CP, et al. Insights into the role of platelet-derived growth factors: Implications for Parkinson's disease pathogenesis and treatment[J]. Front Aging Neurosci, 2022, 14:890509. doi: 10.3389/fnagi.2022.890509.
[4]	Yang L, Ren S, Lou L, et al. A bioinformatics analysis and experimental validation of PDGFD as a promising diagnostic biomarker for acute myeloid leukemia[J]. Sci Rep, 2025, 15(1):14862.doi:10.1038/s41598-025-99038-0.
[5]	Isabelle C, Boles A, Chakravarti N, et al. Cytokines in the pathogenesis of large granular lymphocytic leukemia[J]. Front Oncol, 2022, 12: 849917. doi:10.3389/fonc.2022.849917.
[6]	杨超, 宋子毅, 王昌鑫, 等. 血小板源性生长因子C:脏器纤维化治疗的新兴靶点[J]. 生物化学与生物物理进展, 2025, 52(5):1059-1069. doi:10.16476/j.pibb.2024.0463.
[7]	Yao L, Zhao R, He S, et al. Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway[J/OL]. Phytomedicine, 2022, 106: 154414. doi:10.1016/j.phymed.2022.154414.
[8]	Firat EAM, Buhl EM, Bouteldja N, et al. PDGF-D is dispensable for the development and progression of murine alport syndrome[J]. Am J Pathol, 2024, 194(5): 641-655. doi:10.1016/j.ajpath.2023.12.009. pmid: 38309427
[9]	Seikrit C, Henkel C, van Roeyen CR, et al. Biological responses to PDGF-AA versus PDGF-CC in renal fibroblasts[J]. Nephrol Dial Transplant, 2012, 28(4): 889-900. doi:10.1093/ndt/gfs509.
[10]	周玲, 秦伟. 干扰素α-2b致慢性粒细胞白血病患者膜性肾病1例并文献复习[J]. 中国中西医结合肾病杂志, 2019, 20(11):1017-1018.
[11]	d'Izarny-Gargas T, Isnard P, Boudhabhay I, et al. The spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms[J]. Kidney Int, 2023, 104(6):1206-1218. doi: 10.1016/j.kint.2023.09.010.
[12]	徐荣香, 杨建民. 慢性粒细胞性白血病合并IgA肾病1例报告[J]. 中国血液流变学杂志, 2003, (2):201.
[13]	Aydın Ö, Kaynar K, Güvercin B. Membranous glomerulopathy secondary to chronic myeloid leukemia[J]. Hippokratia, 2021, 25(4):175-176. pmid: 36743864
[14]	Senapati J, Sasaki K, Issa GC, et al. Management of chronic myeloid leukemia in 2023-common ground and common sense[J]. Blood Cancer J, 2023, 13(1):58.doi:10.1038/s41408-023-00823-9. pmid: 37088793
[15]	王研, 王小玲, 吕国庆, 等. 慢性髓细胞性白血病酪氨酸激酶抑制剂优化治疗的研究进展[J]. 山东医药, 2023, 63(13):112-115.
[16]	Ruebner RL, Copelovitch L, Evageliou NF, et al. Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric malignancy: Case series and review of the literature[J]. Pediatr Nephrol, 2013, 29(5): 863-869. doi:10.1007/s00467-013-2696-0.
[17]	Lee HS, Wu HHL, Ponnusamy A, et al. Is there a diagnostic and prognostic role for anti-nephrin autoantibodies in diabetic nephropathy?[J]. Antibodies (Basel), 2025, 14(1): 25. doi:10.3390/antib14010025.
[18]	Ollero M, Sahali D. Inhibition of the VEGF signalling pathway and glomerular disorders[J]. Nephrol Dial Transplant, 2014, 30(9): 1449-1455. doi:10.1093/ndt/gfu368.
[19]	Furuto Y, Hashimoto H, Namikawa A, et al. Focal segmental glomerulosclerosis lesion associated with inhibition of tyrosine kinases by lenvatinib: A case report[J]. BMC Nephrol, 2018, 19(1):273.doi:10.1186/s12882-018-1074-3. pmid: 30340546
[20]	Shyam Sunder S, Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: Pathophysiology, mechanisms and clinical management[J]. Signal Transduct Target Ther, 2023, 8(1):262. doi:10.1038/s41392-023-01469-6.
[21]	Kandula P, Agarwal R. Proteinuria and hypertension with tyrosine kinase inhibitors[J/OL]. Kidney Int, 2011, 80(12): 1271-1277. doi:10.1038/ki.2011.288.
[22]	Wallace E, Lyndon W, Chumley P, et al. Dasatinib-induced nephrotic-range proteinuria[J]. Am J Kidney Dis, 2013, 61(6): 1026-1031. doi:10.1053/j.ajkd.2013.01.022. pmid: 23540262