利妥昔单抗与他克莫司在膜性肾病中的临床应用

陈博文; 吴雪平; 刘磊; 陈卫东

doi:10.16766/j.cnki.issn.1674-4152.003955

利妥昔单抗与他克莫司在膜性肾病中的临床应用

doi: 10.16766/j.cnki.issn.1674-4152.003955

蚌埠医科大学第一附属医院肾内科，安徽蚌埠 233004

基金项目:

安徽省重点研究与开发计划项目 202004j07020011

蚌埠医学院自然科学重点项目 2021byzd116

详细信息

通讯作者:
陈卫东，E-mail：cwd2012@163.com

中图分类号: R692
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出版历程
- 收稿日期: 2024-09-20
- 网络出版日期: 2025-06-30

Comparison of the efficacy of rituximab and tacrolimus in the treatment of idiopathic membranous nephropathy

Department of Nephrology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的比较中高危组膜性肾病患者应用2种治疗方案(利妥昔单抗与小剂量糖皮质激素联合他克莫司)的疗效及安全性。方法选取蚌埠医科大学第一附属医院肾病科2020年1月—2023年6月收治的明确诊断为特发性膜性肾病，且为磷脂酶A2受体(PLA2R)相关性膜性肾病，结合临床表现，诊断为中风险组或高风险组的患者113例。根据治疗方案不同分为利妥昔单抗组(46例，应用利妥昔单抗治疗)和他克莫司组(67例，小剂量糖皮质激素联合他克莫司治疗)。观察2组患者的血清白蛋白、24小时尿蛋白定量、血PLA2R抗体在治疗前及治疗后3个月、6个月、12个月的变化，对比2组治疗总有效率、复发率、不良反应发生情况。结果 2组患者一般资料比较差异均无统计学意义(P>0.05)。治疗3个月、6个月他克莫司组24小时尿蛋白定量分别为3.30(1.46, 4.43)g、1.35(0.62, 2.93)g，与利妥昔单抗组[4.08(3.05, 4.86)g、2.19(1.03, 3.95)g]比较，差异均有统计学意义(P < 0.05)。2组治疗12个月总缓解率差异无统计学意义(P>0.05)；利妥昔单抗组免疫学缓解率(80.43%，37/46)较他克莫司组(77.61%, 52/67)稍高，但差异无统计学意义；利妥昔单抗组复发率低于他克莫司组，差异有统计学意义(P < 0.05)。利妥昔单抗组不良反应发生率(8.70%，4例)低于他克莫司组(25.37%，17例)。结论利妥昔单抗与他克莫司均能有效缓解特发性膜性肾病，但他克莫司组治疗起效较快，利妥昔单抗组免疫学缓解率更高，有效持续时间长，副作用较少，复发率低。
- 膜性肾病 /
- 利妥昔单抗 /
- 他克莫司 /
- 糖皮质激素 /
- 不良反应
Abstract: Objective To compare the efficacy and safety of two treatment regimens (rituximab and a small amount of glucocorticoid combined with tacrolimus) for membranous nephropathy in moderate and high risk groups. Methods Patients diagnosed with idiopathic membranous nephropathy and phospholipase A2 receptor (PLA2R)-associated membranous nephropathy, who were admitted to the Department of Nephrology at the First Affiliated Hospital of Bengbu Medical University, between January 2020 and June 2023 were selected as medium risk or high risk groups based on clinical manifestations. In accordance with the divergent treatment regimens, the subjects were categorized as follows: the rituximab group underwent rituximab treatment, the tacrolimus group received a low-dose glucocorticoid in combination with tacrolimus. The alterations in serum albumin, 24-hour urinary protein quantity, blood PLA2R antibody, prior to treatment, and at 3 months, 6 months and 12 months following-treatments were observed in both groups. The overall effective rate, recurrence rate, and adverse reactions of the two groups were then compared. Results A subsequent investigation revealed no significant difference in the general data between the two groups (P>0.05). The quantitative values of 24-hour urinary protein in the Tacrolimus group after 3 and 6 months of treatment [3.30 (1.46, 4.43) g, 1.35 (0.62, 2.93) g] were superior to those of the RTX group [4.08 (3.05, 4.86) g, 2.19 (1.03, 3.95) g, P < 0.05]. The total remission rate after 12 months of treatment was not statistically significant (P>0.05). The immunological remission rate of 80.43% (37/46) in the rituximab group was marginally higher than 77.61% (52/67) observed in the tacrolimus group; however, this difference did not reach statistical significance. Notably, the recurrence rate in the rituximab group was significantly lower than that observed in the tacrolimus group, with statistical significance (P < 0.05). With regard to adverse reactions, the rate of 8.70% (4 cases) in the rituximab group was lower than the 25.37% (17 cases) observed in the tacrolimus group. Conclusion It has been demonstrated that both rituximab and tacrolimus are effective in the treatment of idiopathic membranous nephropathy. However, it is evident that tacrolimus-treated patients exhibit a more rapid treatment effect, while those administered rituximab demonstrate a higher immunological remission rate and longer effective duration of action. Furthermore, rituximab-treated patients exhibit a reduced incidence of side effects and a lower recurrence rate.
- Membranous nephropathy /
- Rituximab /
- Tacrolimus /
- Glucocorticoid /
- Adverse reaction

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表 1 2组特发性膜性肾病患者一般资料比较

Table 1. Comparison of general information between two groups of patients with idiopathic membranous nephropathy

组别	例数	性别[例(%)]		年龄(x±s，岁)		体重(x±s，kg)	血肌酐(x±s, μmol/L)	尿酸(x±s, μmol/L)
组别	例数	男性	女性	年龄(x±s，岁)		体重(x±s，kg)	血肌酐(x±s, μmol/L)	尿酸(x±s, μmol/L)
利妥昔单抗组	46	33(71.7)	13(28.3)	49.65±13.41		71.93±15.86	65.10±5.63	336.61±89.09
他克莫司组	67	42(62.7)	25(37.3)	48.81±13.28		73.07±14.87	65.40±5.57	331.19±78.12
统计量		1.001^a		0.331^b		0.390^b	0.273^b	0.342^b
P值		0.317		0.741		0.698	0.785	0.733

组别	例数	PLA2R(x±s, RU/mL)		膜性肾病分期[例(%)]			糖尿病[例(%)]	高血压[例(%)]
组别	例数	PLA2R(x±s, RU/mL)		Ⅰ期	Ⅱ期	Ⅲ期	糖尿病[例(%)]	高血压[例(%)]
利妥昔单抗组	46	132.22(39.75, 270.98)		9(19.6)	30(65.2)	7(15.2)	4(8.7)	2(4.3)
他克莫司组	67	191.33(83.76, 266.68)		9(13.4)	47(70.1)	11(16.4)	2(3.0)	5(7.5)
统计量		-1.061^c		0.676^c			0.816^a	0.077^a
P值		0.289		0.499			0.366	0.781
注：^a为χ²值，^b为t值，^c为Z值。

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表 2 2组特发性膜性肾病患者治疗前后血清白蛋白水平比较(x±s, g)

Table 2. Comparison of serum albumin levels before and after treatment between two groups of patients with idiopathic membranous nephropathy (x±s, g)

组别	例数	治疗前	治疗3个月	治疗6个月	治疗12个月	F值	P值
利妥昔单抗组	46	23.33±5.14	28.75±5.88^a	32.41±5.86^ab	37.04±7.29^abc	62.559	< 0.001
他克莫司组	67	24.26±4.48	33.81±5.75^a	36.06±5.80^ab	39.05±6.90^abc	108.982	< 0.001
F值		1.021	4.551	3.271	1.490
P值		0.309	< 0.001	0.001	0.139
注：F_时点=159.182，P < 0.001；F_交互=3.590，P=0.021；F_组别=14.197，P < 0.001。与同组治疗前比较，^aP < 0.05；与治疗3个月比较，^bP < 0.05；与治疗6个月比较，^cP < 0.05。

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表 3 2组患者治疗前后24小时尿蛋白水平比较[M(P₂₅, P₇₅), g]

Table 3. Comparison of 24-hour urine protein levels before and after treatment between two groups of idiopathic membranous nephropathy patients[M(P₂₅, P₇₅), g]

组别	例数	治疗前	治疗3个月	治疗6个月	治疗12个月	Waldχ²	P值
利妥昔单抗组	46	5.21(4.45, 7.14)	4.08(3.05, 4.86)^a	2.19(1.03, 3.95)^ab	1.32(0.39, 3.69)^abc	107.511	< 0.001
他克莫司组	67	5.31(4.39, 6.89)	3.30(1.46, 4.43)^a	1.35(0.62, 2.93)^ab	0.94(0.35, 2.16)^abc	233.231	< 0.001
Waldχ²		0.020	7.907	4.359	2.208
P值		0.887	0.005	0.037	0.137
注：Waldχ_时点²=302.466，P_时点 < 0.001；Waldχ_交互²=6.072，P_交互=0.108；Waldχ_分组²=5.250，P_分组=0.024。与同组治疗前比较，^aP < 0.05；与治疗3个月比较，^bP < 0.05；与治疗6个月比较，^cP < 0.05。

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表 4 2组特发性膜性肾病患者治疗效果比较

Table 4. Comparison of treatment effects between the two groups of idiopathic membranous nephropathy patients

组别	例数	疗效(例)			总有效率(%)	免疫学缓解率(%)	复发率(%)
组别	例数	完全缓解	部分缓解	无效	总有效率(%)	免疫学缓解率(%)	复发率(%)
利妥昔单抗组	46	10	22	14	69.57(32/46)	80.43(37/46)	2.17(1/46)
他克莫司组	67	19	35	13	80.60(54/67)	77.61(52/67)	16.42(11/67)
统计量			1.300^a		1.825^b	0.130^b	4.426^b
P值			0.194		0.177	0.719	0.035
注：^a为Z值，^b为χ²值。

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表 5 2组特发性膜性肾病患者不良反应发生情况比较[例(%)]

Table 5. Comparison of adverse reactions between two groups of idiopathic membranous nephropathy patients

组别	例数	感染	肾功能损伤	肝功能损伤	血糖升高	输注反应	胃肠道反应	高尿酸血症	合计
利妥昔单抗组	46	2(4.35)	0	0	0	2(4.35)	0	0	4(8.70)
他克莫司组	67	3(4.48)	2(2.99)	3(4.48)	3(4.48)	0	3(4.48)	2(2.99)	17(25.37)
注：2组总不良反应发生率比较，χ²=5.014，P=0.025。

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