狼疮性肾炎患者血清补体C3、C4动态变化与肾功能进展及预后的相关性研究

doi:10.3877/cma.j.issn.2095-3216.2026.05.003

目的

探讨狼疮性肾炎患者血清补体C3、C4动态变化与肾功能进展及预后的相关性。

方法

回顾性纳入2022年1月至2025年1月经肾活检确诊的狼疮性肾炎患者。收集基线(第0天)、随访0~180 d内各时间点的临床、病理及血清补体C3、C4检测数据，计算0~180 d补体的相对变化幅度与时间加权均值。根据基线及第180天补体水平将患者分为持续正常型、恢复型、持续降低型、新发降低型。以180 d作为界标起点进行界标分析，采用Kaplan-Meier法、多因素Cox回归模型，并采用LASSO-Cox回归开展敏感性分析，评估补体纵向变化特征与肾功能进展复合终点的关联。

结果

本研究共纳入狼疮性肾炎患者148例，中位随访19.80个月；其中32例(21.62%)出现肾功能进展，设为进展组，其余116例为未进展组。与未进展组比较，进展组基线C3、C4水平更低(P均<0.05)；进展组C3、C4持续降低型患者占比高于未进展组(P均<0.05)；C3、C4持续降低型患者肾功能无进展率最低(P<0.05)。校正混杂因素后，C3持续降低型为肾功能进展的独立相关因素(HR＝3.120，95%CI：1.051~9.270，P＝0.040)；C4相关指标与肾功能进展无显著关联(P均>0.05)。LASSO-Cox敏感性分析验证了本研究结果的稳健性。

结论

血清补体C3的动态变化，尤其是持续降低表型，与狼疮性肾炎患者远期肾功能进展风险独立相关。动态监测补体C3水平有助于狼疮性肾炎的风险分层及预后评估。

关键词: 狼疮性肾炎, 补体C3, 动态变化, 肾功能进展, 预后

Objective

To explore the correlation between dynamic changes of serum complement C3 and C4 and renal function progression as well as prognosis in patients with lupus nephritis.

Methods

Patients with lupus nephritis diagnosed by renal biopsy between January 2022 and January 2025 were retrospectively enrolled. Clinical, pathological, and serum complement C3 and C4 data at baseline (Day 0) and all time points within the 0-180-day follow-up period were collected. The relative change amplitude and time-weighted mean of complement levels from Day 0 to Day 180 were calculated. Patients were classified into the persistently normal group, the recovered group, the persistently reduced group, and the newly reduced group according to complement levels at baseline and Day 180. Landmark analysis was performed with Day 180 as the landmark time point. The Kaplan-Meier method and multivariate Cox regression model were used, and LASSO-Cox regression was adopted for sensitivity analysis to assess the association between longitudinal changes in complement levels and the composite endpoint of renal function progression.

Results

A total of 148 patients with lupus nephritis were enrolled in this study, with a median follow-up of 19.80 months. Among them, 32 patients (21.62%) developed renal function progression and were assigned to the progression group, and the remaining 116 patients were included in the non-progression group. Compared with the non-progression group, the progression group had lower baseline levels of complement C3 and C4 (all P<0.05). The proportion of patients with persistently reduced C3 and C4 in the progression group was higher than that in the non-progression group (all P<0.05). Patients with persistently reduced C3 and C4 exhibited the lowest renal progression-free rate (P<0.05). After adjustment for confounding factors, the persistently reduced C3 phenotype was independently associated with renal function progression (HR=3.120, 95%CI: 1.051-9.270, P=0.040). Indicators related to C4 showed no significant association with renal function progression (all P>0.05). LASSO-Cox sensitivity analysis verified the robustness of the findings in this study.

Conclusion

Dynamic change in serum complement C3, especially the persistently reduced phenotype, is independently associated with the long-term risk of renal function progression in patients with lupus nephritis. Dynamic monitoring of complement C3 level contributes to risk stratification and prognostic evaluation of lupus nephritis.

Key words: Lupus nephritis, Complement C3, Dynamic change, Renal function progression, Prognosis

表1 两组狼疮性肾炎患者线特征比较

变量	肾功能进展组(32例)	未进展组(116例)	t/χ²值	P值
年龄(岁)	41.52±12.84	35.23±11.97	2.635^a	0.009
女性[例(%)]	27(84.38)	99(85.34)	0.019^b	0.891
体质量指数(kg/m²)	22.65±3.22	23.08±3.47	0.635^a	0.526
SLE病程(年)	4.83±3.71	3.79±3.02	1.641^a	0.103
SLEDAI评分(分)	14.56±5.11	11.84±4.93	2.733^a	0.007
高血压[例(%)]	19(59.38)	40(34.48)	6.287^b	0.012
糖尿病[例(%)]	3(9.38)	7(6.03)	0.427^b	0.513
抗双链DNA抗体(IU/mL)	158.46±90.35	107.82±79.64	3.142^a	0.002
C3(g/L)	0.48±0.15	0.62±0.18	4.069^a	<0.001
C4(g/L)	0.07±0.03	0.11±0.05	4.332^a	<0.001
血清肌酐(μmol/L)	119.75±58.46	83.61±35.27	4.375^a	<0.001
eGFR[ml/(min·1.73 m²)]	56.83±24.15	85.26±27.53	5.311^a	<0.001
白蛋白(g/L)	26.94±5.63	31.25±6.28	3.526^a	0.001
24 h尿蛋白(g/24 h)	3.88±2.31	2.47±1.82	3.655^a	<0.001
尿沉渣红细胞(个/HPF)	41.56±28.73	28.15±21.44	2.904^a	0.004
活动指数(分)	8.16±2.93	6.38±2.55	3.422^a	0.001
慢性指数(分)	4.38±2.05	3.01±1.74	3.836^a	<0.001
ISN/RPS分型[例(%)]			11.193^b	0.011
Ⅲ型	2(6.25)	23(19.83)
Ⅳ型	18(56.25)	37(31.90)
Ⅴ型	2(6.25)	28(24.14)
混合型(Ⅲ＋Ⅴ、Ⅳ＋Ⅴ)	10(31.25)	28(24.14)
诱导治疗方案[例(%)]			13.881^b	0.003
糖皮质激素联合吗替麦考酚酯	6(18.75)	49(42.24)
糖皮质激素联合静脉环磷酰胺	18(56.25)	27(23.28)
糖皮质激素联合他克莫司	3(9.38)	21(18.10)
糖皮质激素联合吗替麦考酚酯与他克莫司	5(15.62)	19(16.38)

表1 两组狼疮性肾炎患者线特征比较

变量	肾功能进展组(32例)	未进展组(116例)	t/χ²值	P值
年龄(岁)	41.52±12.84	35.23±11.97	2.635^a	0.009
女性[例(%)]	27(84.38)	99(85.34)	0.019^b	0.891
体质量指数(kg/m²)	22.65±3.22	23.08±3.47	0.635^a	0.526
SLE病程(年)	4.83±3.71	3.79±3.02	1.641^a	0.103
SLEDAI评分(分)	14.56±5.11	11.84±4.93	2.733^a	0.007
高血压[例(%)]	19(59.38)	40(34.48)	6.287^b	0.012
糖尿病[例(%)]	3(9.38)	7(6.03)	0.427^b	0.513
抗双链DNA抗体(IU/mL)	158.46±90.35	107.82±79.64	3.142^a	0.002
C3(g/L)	0.48±0.15	0.62±0.18	4.069^a	<0.001
C4(g/L)	0.07±0.03	0.11±0.05	4.332^a	<0.001
血清肌酐(μmol/L)	119.75±58.46	83.61±35.27	4.375^a	<0.001
eGFR[ml/(min·1.73 m²)]	56.83±24.15	85.26±27.53	5.311^a	<0.001
白蛋白(g/L)	26.94±5.63	31.25±6.28	3.526^a	0.001
24 h尿蛋白(g/24 h)	3.88±2.31	2.47±1.82	3.655^a	<0.001
尿沉渣红细胞(个/HPF)	41.56±28.73	28.15±21.44	2.904^a	0.004
活动指数(分)	8.16±2.93	6.38±2.55	3.422^a	0.001
慢性指数(分)	4.38±2.05	3.01±1.74	3.836^a	<0.001
ISN/RPS分型[例(%)]			11.193^b	0.011
Ⅲ型	2(6.25)	23(19.83)
Ⅳ型	18(56.25)	37(31.90)
Ⅴ型	2(6.25)	28(24.14)
混合型(Ⅲ＋Ⅴ、Ⅳ＋Ⅴ)	10(31.25)	28(24.14)
诱导治疗方案[例(%)]			13.881^b	0.003
糖皮质激素联合吗替麦考酚酯	6(18.75)	49(42.24)
糖皮质激素联合静脉环磷酰胺	18(56.25)	27(23.28)
糖皮质激素联合他克莫司	3(9.38)	21(18.10)
糖皮质激素联合吗替麦考酚酯与他克莫司	5(15.62)	19(16.38)

表2 补体C3、C4动态指标在两组间比较

指标	肾功能进展组(32例)	未进展组(116例)	t/Z值	P值
C3_180 d(g/L)	0.69±0.17	0.84±0.21	－3.723^a	<0.001
C4_180 d(g/L)	0.10±0.03	0.14±0.05	－4.451^a	<0.001
ΔC3_6m(%)	28.50(6.30, 48.20)	43.70(18.50, 68.90)	－2.557^b	0.011
ΔC4_6m(%)	25.00(－2.50, 45.70)	48.30(20.80, 72.60)	－3.418^b	0.001
C3时间加权均值(g/L)	0.62(0.52, 0.74)	0.75(0.63, 0.86)	－3.204^b	0.001
C4时间加权均值(g/L)	0.09(0.07, 0.12)	0.12(0.09, 0.15)	－3.562^b	<0.001

表2 补体C3、C4动态指标在两组间比较

指标	肾功能进展组(32例)	未进展组(116例)	t/Z值	P值
C3_180 d(g/L)	0.69±0.17	0.84±0.21	－3.723^a	<0.001
C4_180 d(g/L)	0.10±0.03	0.14±0.05	－4.451^a	<0.001
ΔC3_6m(%)	28.50(6.30, 48.20)	43.70(18.50, 68.90)	－2.557^b	0.011
ΔC4_6m(%)	25.00(－2.50, 45.70)	48.30(20.80, 72.60)	－3.418^b	0.001
C3时间加权均值(g/L)	0.62(0.52, 0.74)	0.75(0.63, 0.86)	－3.204^b	0.001
C4时间加权均值(g/L)	0.09(0.07, 0.12)	0.12(0.09, 0.15)	－3.562^b	<0.001

表3 C3与C4动态分型在两组间分布

分型	肾功能进展组(32例)	未进展组(116例)	χ²值	P值
C3动态分型[例(%)]			9.909	0.019
持续正常型	3(9.38)	27(23.28)
恢复型	7(21.88)	43(37.07)
持续降低型	16(50.00)	28(24.14)
新发降低型	6(18.75)	18(15.52)
C4动态分型[例(%)]			11.601	0.009
持续正常型	4(12.50)	36(31.03)
恢复型	6(18.75)	38(32.76)
持续降低型	15(46.88)	25(21.55)
新发降低型	7(21.88)	17(14.66)

表3 C3与C4动态分型在两组间分布

分型	肾功能进展组(32例)	未进展组(116例)	χ²值	P值
C3动态分型[例(%)]			9.909	0.019
持续正常型	3(9.38)	27(23.28)
恢复型	7(21.88)	43(37.07)
持续降低型	16(50.00)	28(24.14)
新发降低型	6(18.75)	18(15.52)
C4动态分型[例(%)]			11.601	0.009
持续正常型	4(12.50)	36(31.03)
恢复型	6(18.75)	38(32.76)
持续降低型	15(46.88)	25(21.55)
新发降低型	7(21.88)	17(14.66)

图1 按C3和C4动态分型分层的肾功能无进展生存曲线注：A为C3动态分型分层的肾功能无进展生存曲线；B为C4动态分型分层的肾功能无进展生存曲线

表4 不同补体动态分型的肾功能进展事件发生情况与24个月无进展率

分型	肾功能进展事件[例(%)]	24个月肾功能无进展率(%)	log-rank χ²值	P值
C3动态分型			12.668	0.005
持续正常型(30例)	3(10.00)	90.00
恢复型(50例)	7(14.00)	86.00
持续降低型(44例)	16(36.36)	62.35
新发降低型(24例)	6(25.00)	72.12
C4动态分型			13.585	0.004
持续正常型(40例)	4(10.00)	88.38
恢复型(44例)	6(13.64)	85.37
持续降低型(40例)	15(37.50)	60.33
新发降低型(24例)	7(29.17)	70.18

表4 不同补体动态分型的肾功能进展事件发生情况与24个月无进展率

分型	肾功能进展事件[例(%)]	24个月肾功能无进展率(%)	log-rank χ²值	P值
C3动态分型			12.668	0.005
持续正常型(30例)	3(10.00)	90.00
恢复型(50例)	7(14.00)	86.00
持续降低型(44例)	16(36.36)	62.35
新发降低型(24例)	6(25.00)	72.12
C4动态分型			13.585	0.004
持续正常型(40例)	4(10.00)	88.38
恢复型(44例)	6(13.64)	85.37
持续降低型(40例)	15(37.50)	60.33
新发降低型(24例)	7(29.17)	70.18

表5 多因素Cox回归分析结果

变量	β	SE	Wald χ²值	HR(95%CI)	P值
C4动态分型
持续正常型	参考
恢复型	0.058	0.602	0.009	1.060(0.326~3.447)	0.923
持续降低型	0.663	0.451	2.156	1.941(0.802~4.699)	0.142
新发降低型	0.512	0.467	1.201	1.669(0.668~4.170)	0.273
C3动态分型
持续正常型	参考
恢复型	0.081	0.575	0.020	1.084(0.351~3.346)	0.888
持续降低型	1.138	0.555	4.198	3.120(1.051~9.270)	0.040
新发降低型	0.932	0.557	2.805	2.540(0.854~7.569)	0.094
ΔC3_6m(每10%)	－0.159	0.076	4.382	0.853(0.734~0.990)	0.036
C3时间加权均值(每0.10 g/L)	－0.352	0.159	4.900	0.703(0.514~0.961)	0.027
ΔC4_6m(每10%)	－0.086	0.082	1.102	0.918(0.784~1.075)	0.290
C4时间加权均值(每0.01 g/L)	－0.050	0.060	0.694	0.951(0.845~1.070)	0.401

表5 多因素Cox回归分析结果

变量	β	SE	Wald χ²值	HR(95%CI)	P值
C4动态分型
持续正常型	参考
恢复型	0.058	0.602	0.009	1.060(0.326~3.447)	0.923
持续降低型	0.663	0.451	2.156	1.941(0.802~4.699)	0.142
新发降低型	0.512	0.467	1.201	1.669(0.668~4.170)	0.273
C3动态分型
持续正常型	参考
恢复型	0.081	0.575	0.020	1.084(0.351~3.346)	0.888
持续降低型	1.138	0.555	4.198	3.120(1.051~9.270)	0.040
新发降低型	0.932	0.557	2.805	2.540(0.854~7.569)	0.094
ΔC3_6m(每10%)	－0.159	0.076	4.382	0.853(0.734~0.990)	0.036
C3时间加权均值(每0.10 g/L)	－0.352	0.159	4.900	0.703(0.514~0.961)	0.027
ΔC4_6m(每10%)	－0.086	0.082	1.102	0.918(0.784~1.075)	0.290
C4时间加权均值(每0.01 g/L)	－0.050	0.060	0.694	0.951(0.845~1.070)	0.401

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Study on the correlation between dynamic changes of serum complement C3 and C4 and renal function progression as well as prognosis in patients with lupus nephritis

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Study on the correlation between dynamic changes of serum complement C3 and C4 and renal function progression as well as prognosis in patients with lupus nephritis