贫血在系统判定ANCA相关性小血管炎患者病情及预后中的作用

doi:10.3969/j.issn.1004-583X.2025.09.005

摘要/Abstract

摘要：

目的分析抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)相关性血管炎(ANCA-associated vasculitis,AAV)患者贫血发生的原因,评价初始贫血程度、贫血类型及贫血治疗反应对判定AAV患者病情的价值及与肾脏预后和全因死亡率的关系。方法本研究纳入2013-2022年在青岛大学附属医院确诊为AAV患者157例,根据初始就诊时的血红蛋白水平分为非贫血组、轻度贫血组、中重度贫血组,详细分析AAV贫血发生的原因,动态观察不同原因的贫血经治疗后的反应及变化特点,据初诊基线与随访终点的血红蛋白值高(H)低(L)变化,将患者分为HH、HL、LH、LL四组,对各组患者进行肾脏结局和全因死亡率分析。结果符合纳入标准的157例AAV患者中,女性82例(52.2%),男性75例(47.8%),年龄20~86岁,中位年龄67岁。髓过氧化物酶(MPO)-ANCA阳性者137例,蛋白酶3(PR3)-ANCA阳性者18例,双阳性者2例。平均随访时间(37±30)个月。研究结束时28例进展为终末期肾功能衰竭,死亡31例。AAV初诊时贫血十分常见,仅11例无贫血,轻度贫血67例,中重度贫血79例。贫血原因前四位分别为炎症性贫血、肾性贫血、感染性贫血、心肾贫血综合征;单一原因贫血少见(9/146,6.16%),复合型贫血常见(137/146,93.84%)。致贫血原因累加数量越多,肾脏预后越差。据初诊基线与随访终点的血红蛋白值高(H)低(L)变化,肾脏结局和全因死亡率分析发现,HH组肾脏存活率最高,全因死亡率最低;LL组更易进展为终末期肾功能衰竭(P<0.05),全因死亡率最高(P<0.05)。结论 AAV中常见的贫血是AAV中活跃且有价值的系统判定病情及预后的监测指标,贫血发生与疾病活动性(BVAS评分)显著相关,复合原因贫血最多见。贫血治疗反应是肾功能恶化及全因死亡的独立预测因子。

关键词: 抗中性粒细胞胞浆抗体相关性血管炎, 贫血, 综合评价, 预后

Abstract:

Objective To investigate the etiology of anemia in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to evaluate the value of baseline anemia severity, anemia subtypes, therapeutic responses in determining the severity of AAV as well as their association with renal prognosis and all-cause mortality. Methods A total of 157 AAV patients diagnosed in the Affiliated Hospital of Qingdao University between 2013 and 2022 were enrolled. Patients were stratified into the non-anemia, mild anemia, and moderate-severe anemia groups based on baseline hemoglobin levels. Etiologies of anemia were systematically analyzed. Dynamic treatment response and changes in hemoglobin levels were tracked post-treatment. Patients were categorized into four groups (HH, HL, LH, LL) according to baseline-to-endpoint hemoglobin trends (H: high; L: low). Renal outcomes and mortality were compared across groups. Results Among 157 AAV patients, there were 82 (52.2%) female and 75 (47.8%) male patients, with a median age of 67 (20-86) years. A total of 137 myeloperoxidase (MPO)-ANCA-positive, 18 proteinase 3 (PR3)-ANCA-positive, and 2 dual-positive cases were detected. The mean follow-up duration was 37±30 months. By study endpoint, 28 patients progressed to end-stage renal disease (ESRD), and 31 died. Anemia was prevalent at baseline, with only 11 non-anemic patients. A total of 67 had mild anemia, and 79 had moderate-to-severe anemia. The top 4 etiologies of anemia included anemia of inflammation (AI), renal anemia, infection-related anemia, and cardiorenal anemia syndrome. Single-etiology anemia was rare (9/146, 6.16%), while multifactorial anemia predominated (137/146, 93.84%). A higher number of etiological factors of anemia correlated with worse renal prognosis. Hemoglobin trajectory analysis revealed that the HH group (persistently high hemoglobin) exhibited the lowest all-cause mortality and highest renal survival, whereas the LL group (persistently low hemoglobin) had the highest incidence of ESRD progression (P<0.05) and mortality rate (P<0.05). Conclusion Anemia in AAV is a dynamic and clinically significant biomarker for disease activity and prognosis. Its occurrence strongly correlates with disease activity (the Birmingham Vasculitis Activity Score [BVAS]) and is predominantly multifactorial. Therapeutic response to anemia correction serves as an independent predictor of renal function deterioration and all-cause mortality.

Key words: ANCA-associated vasculitis, anemia, comprehensive evaluation, prognosis

中图分类号:

R543

陈璐, 亓晓菁, 韩润鸿, 邢广群. 贫血在系统判定ANCA相关性小血管炎患者病情及预后中的作用[J]. 临床荟萃, 2025, 40(9): 801-810.

Chen Lu, Qi Xiaojing, Han Runhong, Xing Guangqun. The role of anemia in evaluating disease severity and prognosis of ANCA-associated vasculitis[J]. Clinical Focus, 2025, 40(9): 801-810.

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链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2025.09.005

https://www.lchc.cn/CN/Y2025/V40/I9/801

图/表 11

表1 贫血原因分类

Tab.1 Classification of causes of anemia

贫血类型	诊断标准
缺铁性贫血	血清铁蛋白<10 μg/L(女)/<15 μg/L(男)或转铁蛋白饱和度<16%、血清铁蛋白<30 μg/L^[13]。
炎症性贫血	血清铁低、转铁蛋白饱和度<20%、铁蛋白>100 μg/L、CRP/红细胞沉降率(erythrocyte sedimentation rate, ESR)升高、正常细胞正色素性贫血^[9,14]。
肾性贫血	肾功能下降、促红细胞生成素减少、红细胞寿命缩短^[15-16]。
感染性贫血	临床/实验室/影像学证据支持的感染,伴抗生素治疗。
心肾贫血综合征	心力衰竭、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)<60 ml/(min·1.73m²)、HGB<130 g/L(男)或<120 g/L(女) ^[17-18]。
叶酸缺乏性贫血	血清叶酸<3 μg/L^[12]。

表2 初诊时不同HGB水平AAV患者的临床资料及基线特征

Tab.2 Clinical data and baseline characteristics of AAV patients with different HGB levels at the initial diagnosis

项目	非贫血组	轻度贫血组	中重度贫血组	$t$ /χ²/ $Z$ 值	$P$ 值
例数	11	67	79
男/女	5/6	35/32	35/44	0.940	0.625
年龄(岁)	64.0(53.0, 71.0)	68.0(60.0, 75.0)	67.0(60.0, 72.0)	1.792	0.408
初诊HGB(g/L)	133.00±12.78	104.63±10.93	72.65±10.19	255.490	<0.01
MCV(fl)	90.19±2.59	89.72±5.29	89.68±5.44	0.046	0.955
MCH(pg)	30.05±0.76	29.27±1.82	29.25±2.16	2.841	0.242
MCHC(g/L)	333.27±9.48	326.51±16.58	326.13±15.70	1.011	0.366
CRP(mg/L)	1.51(0.66, 9.79)	17.67(0.96, 80.43)	52.30(7.61, 101.08)	10.120	0.006
ESR(mm/h)	14.85(11.33, 21.00)	49.00(23.40, 84.40)	86.40(42.70, 108.00)	24.367	<0.01
SCr(μmol/L)	97.00(82.30, 126.70)	153.45(95.63, 311.98)	542.20(297.50, 784.10)	48.923	<0.01
eGFR[ml/(min·1.73 m²)]	64.68(40.59, 73.54)	32.52(16.39, 54.39)	9.56(6.09, 18.53)	49.006	<0.01
BUN(mmol/L)	5.42(4.78, 8.10)	9.84(6.69, 17.49)	26.50(17.70, 37.45)	55.572	<0.01
UA(mmol/L)	338.22±47.98	382.61±167.98	454.90±153.51	9.911	0.007
ALB(g/L)	36.83±7.34	32.32±5.34	29.33±5.22	11.445	<0.01
DD( μg/L)	270.00(96.25, 530.00)	465.00(257.50, 1062.00)	1410.00(562.00, 3570.00)	34.510	<0.01
24 h尿蛋白定量(g/24 h)	0.91(0.44, 2.34)	1.09(0.30, 1.89)	1.11(0.72, 2.47)	1.701	0.427
尿常规红细胞数(个/μl)	105.15(12.39, 388.48)	63.65(19.62, 250.58)	187.44(48.50, 687.10)	9.675	0.008
PCT(μg/L)	0.13(0.06, 0.20)	0.13(0.07, 0.33)	0.32(0.16, 0.70)	14.040	0.001
CD4绝对计数(cells/μl)	568.00(469.25, 726.00)	478.00(334.00, 806.00)	381.00(183.00, 639.00)	6.069	0.048
C3(g/L)	1.04(0.95, 1.22)	1.03(0.87, 1.23)	0.91(0.77, 1.02)	11.788	0.003
C4(g/L)	0.29±0.08	0.26±0.10	0.23±0.08	3.084	0.049
BNP(ng/L)	101.35(18.50, 670.28)	78.90(42.50, 180.50)	263.30(103.40, 847.60)	11.246	0.004
Hs-TnI(μg/L)	0.004(0.002, 0.018)	0.006(0.003, 0.012)	0.016(0.009, 0.047)	13.774	0.001
EF%	62.00(60.50, 64.50)	63.00(61.00, 64.00)	62.00(58.00, 63.00)	5.139	0.077
叶酸(μg/L)	6.99(5.26, 7.64)	5.13(3.73, 9.64)	5.00(3.05, 12.69)	0.347	0.841
维生素B12(ng/L)	1008.76(598.86, 1815.75)	590.37(430.23, 1028.73)	547.62(356.50, 957.08)	3.153	0.207
结合珠蛋白(g/L)	1.66(1.08, 3.21)	2.02(0.95, 3.03)	1.74(1.17, 2.60)	0.050	0.975
铁蛋白(μg/L)	327.00(60.60, 759.10)	329.60(198.00, 704.22)	436.04(203.50, 737.44)	2.080	0.353
转铁蛋白(g/L)	1.33±0.58	1.60±0.50	1.40±0.39	2.092	0.130
可溶性转铁蛋白受体(mg/L)	0.64(0.39, 1.41)	1.11(0.91, 1.31)	0.87(0.64, 1.05)	8.624	0.013
BVAS	13.36±5.82	14.61±5.36	18.87±5.61	12.927	<0.01
FFS	1.00(1.00, 2.00)	2.00(2.00, 3.00)	3.00(2.00, 3.00)	11.600	0.003
CCI	1.00(1.00, 2.00)	2.00(1.00, 3.00)	4.00(3.00, 4.00)	40.413	<0.01

表2 初诊时不同HGB水平AAV患者的临床资料及基线特征

Tab.2 Clinical data and baseline characteristics of AAV patients with different HGB levels at the initial diagnosis

项目	非贫血组	轻度贫血组	中重度贫血组	$t$ /χ²/ $Z$ 值	$P$ 值
例数	11	67	79
男/女	5/6	35/32	35/44	0.940	0.625
年龄(岁)	64.0(53.0, 71.0)	68.0(60.0, 75.0)	67.0(60.0, 72.0)	1.792	0.408
初诊HGB(g/L)	133.00±12.78	104.63±10.93	72.65±10.19	255.490	<0.01
MCV(fl)	90.19±2.59	89.72±5.29	89.68±5.44	0.046	0.955
MCH(pg)	30.05±0.76	29.27±1.82	29.25±2.16	2.841	0.242
MCHC(g/L)	333.27±9.48	326.51±16.58	326.13±15.70	1.011	0.366
CRP(mg/L)	1.51(0.66, 9.79)	17.67(0.96, 80.43)	52.30(7.61, 101.08)	10.120	0.006
ESR(mm/h)	14.85(11.33, 21.00)	49.00(23.40, 84.40)	86.40(42.70, 108.00)	24.367	<0.01
SCr(μmol/L)	97.00(82.30, 126.70)	153.45(95.63, 311.98)	542.20(297.50, 784.10)	48.923	<0.01
eGFR[ml/(min·1.73 m²)]	64.68(40.59, 73.54)	32.52(16.39, 54.39)	9.56(6.09, 18.53)	49.006	<0.01
BUN(mmol/L)	5.42(4.78, 8.10)	9.84(6.69, 17.49)	26.50(17.70, 37.45)	55.572	<0.01
UA(mmol/L)	338.22±47.98	382.61±167.98	454.90±153.51	9.911	0.007
ALB(g/L)	36.83±7.34	32.32±5.34	29.33±5.22	11.445	<0.01
DD( μg/L)	270.00(96.25, 530.00)	465.00(257.50, 1062.00)	1410.00(562.00, 3570.00)	34.510	<0.01
24 h尿蛋白定量(g/24 h)	0.91(0.44, 2.34)	1.09(0.30, 1.89)	1.11(0.72, 2.47)	1.701	0.427
尿常规红细胞数(个/μl)	105.15(12.39, 388.48)	63.65(19.62, 250.58)	187.44(48.50, 687.10)	9.675	0.008
PCT(μg/L)	0.13(0.06, 0.20)	0.13(0.07, 0.33)	0.32(0.16, 0.70)	14.040	0.001
CD4绝对计数(cells/μl)	568.00(469.25, 726.00)	478.00(334.00, 806.00)	381.00(183.00, 639.00)	6.069	0.048
C3(g/L)	1.04(0.95, 1.22)	1.03(0.87, 1.23)	0.91(0.77, 1.02)	11.788	0.003
C4(g/L)	0.29±0.08	0.26±0.10	0.23±0.08	3.084	0.049
BNP(ng/L)	101.35(18.50, 670.28)	78.90(42.50, 180.50)	263.30(103.40, 847.60)	11.246	0.004
Hs-TnI(μg/L)	0.004(0.002, 0.018)	0.006(0.003, 0.012)	0.016(0.009, 0.047)	13.774	0.001
EF%	62.00(60.50, 64.50)	63.00(61.00, 64.00)	62.00(58.00, 63.00)	5.139	0.077
叶酸(μg/L)	6.99(5.26, 7.64)	5.13(3.73, 9.64)	5.00(3.05, 12.69)	0.347	0.841
维生素B12(ng/L)	1008.76(598.86, 1815.75)	590.37(430.23, 1028.73)	547.62(356.50, 957.08)	3.153	0.207
结合珠蛋白(g/L)	1.66(1.08, 3.21)	2.02(0.95, 3.03)	1.74(1.17, 2.60)	0.050	0.975
铁蛋白(μg/L)	327.00(60.60, 759.10)	329.60(198.00, 704.22)	436.04(203.50, 737.44)	2.080	0.353
转铁蛋白(g/L)	1.33±0.58	1.60±0.50	1.40±0.39	2.092	0.130
可溶性转铁蛋白受体(mg/L)	0.64(0.39, 1.41)	1.11(0.91, 1.31)	0.87(0.64, 1.05)	8.624	0.013
BVAS	13.36±5.82	14.61±5.36	18.87±5.61	12.927	<0.01
FFS	1.00(1.00, 2.00)	2.00(2.00, 3.00)	3.00(2.00, 3.00)	11.600	0.003
CCI	1.00(1.00, 2.00)	2.00(1.00, 3.00)	4.00(3.00, 4.00)	40.413	<0.01

图1 AAV患者不同贫血原因的Venn图

Fig.1 Venn plots of different causes of anemia in AAV patients

表3 不同贫血原因AAV患者的临床特征比较

Tab.3 Comparison of clinical characteristics of AAV patients with different causes of anemia

项目	炎症性贫血( $n$ =146)	肾性贫血( $n$ =133)	感染性贫血( $n$ =61)	心肾贫血综合征( $n$ =40)	叶酸缺乏所致贫血( $n$ =16)	缺铁性贫血( $n$ =11)	失血性贫血( $n$ =8)
人数[例(%)]	146(100.0)	133(91.1)	61(41.8)	40(27.4)	16(11.0)	11(7.5)	8(5.4)
年龄(岁)	67.50(60.00, 74.00)	68.00(60.00, 74.00)	68.00(63.50, 75.00)	69.50(63.25, 79.50)	69.50(59.50, 80.75)	65.00(47.00, 74.00)	64.00(43.75, 70.50)
初诊HGB(g/L)	86.00(71.00, 101.25)	85.00(70.00, 98.50)	87.00(70.00, 101.50)	81.50(66.00, 86.75)	69.00(60.50, 84.50)	85.00(74.00, 103.00)	79.50(54.75, 92.00)
MCV(fl)	90.60(87.95, 93.28)	88.70(85.25, 93.55)	87.60(85.10, 92.70)	90.80(86.68, 94.93)	86.45(84.60, 90.50)	87.40(82.80, 91.20)	91.05(89.15, 94.65)
MCH(pg)	29.45(28.68, 29.75)	29.30(27.85, 30.60)	28.30(27.25, 30.10)	29.70(27.35, 30.65)	28.90(27.75, 30.08)	29.00(26.30, 29.60)	29.80(28.50, 30.38)
MCHC(g/L)	324.50(314.50, 332.50)	328.00(317.00, 336.50)	324.00(309.50, 334.50)	325.50(313.50, 335.00)	327.50(322.50, 338.75)	322.00(310.00, 335.00)	325.50(318.25, 327.50)
CRP(mg/L)	36.02(3.66, 97.84)	28.27(3.02, 98.64)	69.58(15.31, 129.88)	36.41(6.31, 109.15)	91.17(20.32, 151.06)	13.56(2.18, 69.58)	21.41(2.37, 126.99)
ESR(mm/h)	72.00(27.68, 99.25)	74.30(27.45,100.00)	75.10(37.15, 107.00)	55.15(21.40, 99.00)	49.00(30.43, 96.28)	27.00(12.00, 78.80)	39.35(24.33, 98.25)
SCr(μmol/L)	311.00(146.05, 655.70)	364.75(167.45, 691.23)	394.90(163.80, 671.95)	650.20(352.00, 822.70)	705.75(530.95, 975.38)	328.30(146.80, 980.00)	341.20(271.58, 713.80)
eGFR[ml/(min·1.73 m²)]	16.72(7.91, 33.74)	14.71(7.30, 28.28)	13.94(6.22, 27.18)	8.77(5.50, 14.71)	8.32(5.09, 11.52)	12.41(5.51, 35.88)	15.72(9.01, 27.34)
BUN(mmol/L)	19.20(9.19, 29.79)	19.93(11.38, 30.93)	20.00(10.56, 31.75)	29.93(19.58, 42.43)	30.35(22.63, 48.11)	20.00(13.01, 26.59)	20.04(15.22, 32.35)
UA(mmol/L)	423.20(282.50, 525.88)	439.00(304.40, 563.00)	392.80(282.85, 515.70)	472.70(370.35, 637.30)	420.05(275.73, 573.58)	534.70(291.40, 653.00)	472.30(279.00, 534.70)
ALB(g/L)	31.10(26.90, 34.50)	30.70(26.41,34.50)	29.70(25.50, 33.90)	28.42(24.42, 33.70)	28.15(24.01, 30.47)	32.60(29.70, 34.20)	32.95(26.40, 35.60)
DD(μg/L)	780.00(354.00, 2280.00)	820.00(352.00, 2367.50)	859.50(295.75, 1840.00)	1410.00(720.00, 4970.00)	2225.00(1457.50, 5980.00)	470.00(207.00, 1141.00)	2099.00(450.25, 5622.50)
24 h尿蛋白定量(g/24 h)	1.11(0.62, 2.08)	1.11(0.63, 2.08)	0.72(0.31, 1.48)	1.30(0.63, 2.80)	1.79(0.72, 4.01)	0.86(0.22, 2.13)	0.89(0.63, 1.23)
尿常规红细胞数(个/μl)	122.30(30.50, 396.20)	123.40(31.48, 444.20)	79.20(33.60, 227.00)	91.00(31.80, 285.00)	188.00(48.18, 559.10)	228.00(69.80, 489.15)	228.00(26.00, 395.00)
PCT(μg/L)	0.24(0.11, 0.60)	0.25(0.12, 0.63)	0.40(0.13, 0.94)	0.51(0.20, 0.89)	0.57(0.32, 0.94)	0.33(0.29, 1.62)	0.25(0.16, 0.34)
C3(g/L)	0.95(0.81, 1.09)	0.95(0.80, 1.07)	0.97(0.80, 1.18)	0.88(0.64, 0.96)	0.84(0.76, 1.03)	1.00(0.70, 1.15)	0.86(0.62, 1.11)
C4(g/L)	0.24(0.19, 0.29)	0.24(0.18, 0.29)	0.23(0.16, 0.29)	0.20(0.17, 0.27)	0.20(0.14, 0.29)	0.21(0.18, 0.25)	0.19(0.15,0.24)
BNP(ng/L)	159.70(54.58, 644.03)	181.70(62.53, 666.83)	258.75(72.03, 1079.60)	884.90(292.80, 1528.15)	263.00(114.55, 617.03)	180.50(103.40, 652.20)	263.30(77.8, 1895.1)
Hs-TnI(μg/L)	0.012(0.005, 0.042)	0.014(0.006, 0.043)	0.021(0.007, 0.066)	0.037(0.012, 0.089)	0.021(0.008, 0.059)	0.012(0.004, 0.032)	0.026(0.004, 0.160)
EF%	62.00(60.00, 63.00)	62.00(60.00, 63.00)	62.00(60.00, 64.75)	60.00(56.00, 62.00)	62.00(60.00, 63.00)	63.00(61.00, 65.00)	66.00(60.00, 67.00)
叶酸(μg/L)	5.01(3.13, 11.89)	5.01(3.10, 11.89)	6.42(2.57, 12.85)	7.72(2.84, 17.02)	2.09(1.48, 2.55)	10.03(3.51, 19.53)	2.52(1.51, 6.57)
维生素B12(ng/L)	551.63(361.03, 981.50)	547.62(358.75, 1016.73)	677.68(404.65, 1150.90)	677.68(384.77, 1069.51)	687.29(305.46, 1144.62)	648.79(424.54, 1690.57)	316.29(245.81, 502.65)
结合珠蛋白(g/L)	1.83(1.12, 2.64)	1.74(1.08, 2.63)	1.85(1.15, 2.78)	1.76(1.15, 2.57)	1.45(0.66, 2.90)	1.29(0.93, 2.28)	1.64(1.41, 3.45)
铁蛋白(μg/L)	397.65(204.33, 708.26)	386.58(202.65, 715.99)	484.02(191.02, 901.44)	614.35(197.72, 1004.93)	964.50(425.48, 1307.00)	68.58(23.87, 92.82)	187.99(124.84, 1071.75)
转铁蛋白(g/L)	1.45(1.17, 1.72)	1.46(1.17, 1.74)	1.33(1.09, 1.56)	1.25(0.94, 1.55)	1.21(0.90, 1.46)	1.82(1.71, 2.44)	1.61(1.30, 1.72)
可溶性转铁蛋白受体(mg/L)	0.93(0.70, 1.22)	0.92(0.70, 1.22)	0.86(0.63, 1.07)	0.89(0.64, 1.14)	0.76(0.60, 0.90)	1.21(0.98, 1.79)	0.85(0.78, 0.93)
BVAS	16.92±5.88	17.28±5.85	18.11±5.51	20.93±5.37	20.50±5.54	16.18±6.03	20.75±7.74
FFS	2.47±0.96	2.56±0.91	2.66±0.93	3.30±0.72	2.88±0.96	2.36±1.21	2.63±0.92
CCI	3.09±1.36	3.19±1.35	3.43±1.35	4.13±0.97	3.69±0.79	3.45±1.21	3.88±0.64

表3 不同贫血原因AAV患者的临床特征比较

Tab.3 Comparison of clinical characteristics of AAV patients with different causes of anemia

项目	炎症性贫血( $n$ =146)	肾性贫血( $n$ =133)	感染性贫血( $n$ =61)	心肾贫血综合征( $n$ =40)	叶酸缺乏所致贫血( $n$ =16)	缺铁性贫血( $n$ =11)	失血性贫血( $n$ =8)
人数[例(%)]	146(100.0)	133(91.1)	61(41.8)	40(27.4)	16(11.0)	11(7.5)	8(5.4)
年龄(岁)	67.50(60.00, 74.00)	68.00(60.00, 74.00)	68.00(63.50, 75.00)	69.50(63.25, 79.50)	69.50(59.50, 80.75)	65.00(47.00, 74.00)	64.00(43.75, 70.50)
初诊HGB(g/L)	86.00(71.00, 101.25)	85.00(70.00, 98.50)	87.00(70.00, 101.50)	81.50(66.00, 86.75)	69.00(60.50, 84.50)	85.00(74.00, 103.00)	79.50(54.75, 92.00)
MCV(fl)	90.60(87.95, 93.28)	88.70(85.25, 93.55)	87.60(85.10, 92.70)	90.80(86.68, 94.93)	86.45(84.60, 90.50)	87.40(82.80, 91.20)	91.05(89.15, 94.65)
MCH(pg)	29.45(28.68, 29.75)	29.30(27.85, 30.60)	28.30(27.25, 30.10)	29.70(27.35, 30.65)	28.90(27.75, 30.08)	29.00(26.30, 29.60)	29.80(28.50, 30.38)
MCHC(g/L)	324.50(314.50, 332.50)	328.00(317.00, 336.50)	324.00(309.50, 334.50)	325.50(313.50, 335.00)	327.50(322.50, 338.75)	322.00(310.00, 335.00)	325.50(318.25, 327.50)
CRP(mg/L)	36.02(3.66, 97.84)	28.27(3.02, 98.64)	69.58(15.31, 129.88)	36.41(6.31, 109.15)	91.17(20.32, 151.06)	13.56(2.18, 69.58)	21.41(2.37, 126.99)
ESR(mm/h)	72.00(27.68, 99.25)	74.30(27.45,100.00)	75.10(37.15, 107.00)	55.15(21.40, 99.00)	49.00(30.43, 96.28)	27.00(12.00, 78.80)	39.35(24.33, 98.25)
SCr(μmol/L)	311.00(146.05, 655.70)	364.75(167.45, 691.23)	394.90(163.80, 671.95)	650.20(352.00, 822.70)	705.75(530.95, 975.38)	328.30(146.80, 980.00)	341.20(271.58, 713.80)
eGFR[ml/(min·1.73 m²)]	16.72(7.91, 33.74)	14.71(7.30, 28.28)	13.94(6.22, 27.18)	8.77(5.50, 14.71)	8.32(5.09, 11.52)	12.41(5.51, 35.88)	15.72(9.01, 27.34)
BUN(mmol/L)	19.20(9.19, 29.79)	19.93(11.38, 30.93)	20.00(10.56, 31.75)	29.93(19.58, 42.43)	30.35(22.63, 48.11)	20.00(13.01, 26.59)	20.04(15.22, 32.35)
UA(mmol/L)	423.20(282.50, 525.88)	439.00(304.40, 563.00)	392.80(282.85, 515.70)	472.70(370.35, 637.30)	420.05(275.73, 573.58)	534.70(291.40, 653.00)	472.30(279.00, 534.70)
ALB(g/L)	31.10(26.90, 34.50)	30.70(26.41,34.50)	29.70(25.50, 33.90)	28.42(24.42, 33.70)	28.15(24.01, 30.47)	32.60(29.70, 34.20)	32.95(26.40, 35.60)
DD(μg/L)	780.00(354.00, 2280.00)	820.00(352.00, 2367.50)	859.50(295.75, 1840.00)	1410.00(720.00, 4970.00)	2225.00(1457.50, 5980.00)	470.00(207.00, 1141.00)	2099.00(450.25, 5622.50)
24 h尿蛋白定量(g/24 h)	1.11(0.62, 2.08)	1.11(0.63, 2.08)	0.72(0.31, 1.48)	1.30(0.63, 2.80)	1.79(0.72, 4.01)	0.86(0.22, 2.13)	0.89(0.63, 1.23)
尿常规红细胞数(个/μl)	122.30(30.50, 396.20)	123.40(31.48, 444.20)	79.20(33.60, 227.00)	91.00(31.80, 285.00)	188.00(48.18, 559.10)	228.00(69.80, 489.15)	228.00(26.00, 395.00)
PCT(μg/L)	0.24(0.11, 0.60)	0.25(0.12, 0.63)	0.40(0.13, 0.94)	0.51(0.20, 0.89)	0.57(0.32, 0.94)	0.33(0.29, 1.62)	0.25(0.16, 0.34)
C3(g/L)	0.95(0.81, 1.09)	0.95(0.80, 1.07)	0.97(0.80, 1.18)	0.88(0.64, 0.96)	0.84(0.76, 1.03)	1.00(0.70, 1.15)	0.86(0.62, 1.11)
C4(g/L)	0.24(0.19, 0.29)	0.24(0.18, 0.29)	0.23(0.16, 0.29)	0.20(0.17, 0.27)	0.20(0.14, 0.29)	0.21(0.18, 0.25)	0.19(0.15,0.24)
BNP(ng/L)	159.70(54.58, 644.03)	181.70(62.53, 666.83)	258.75(72.03, 1079.60)	884.90(292.80, 1528.15)	263.00(114.55, 617.03)	180.50(103.40, 652.20)	263.30(77.8, 1895.1)
Hs-TnI(μg/L)	0.012(0.005, 0.042)	0.014(0.006, 0.043)	0.021(0.007, 0.066)	0.037(0.012, 0.089)	0.021(0.008, 0.059)	0.012(0.004, 0.032)	0.026(0.004, 0.160)
EF%	62.00(60.00, 63.00)	62.00(60.00, 63.00)	62.00(60.00, 64.75)	60.00(56.00, 62.00)	62.00(60.00, 63.00)	63.00(61.00, 65.00)	66.00(60.00, 67.00)
叶酸(μg/L)	5.01(3.13, 11.89)	5.01(3.10, 11.89)	6.42(2.57, 12.85)	7.72(2.84, 17.02)	2.09(1.48, 2.55)	10.03(3.51, 19.53)	2.52(1.51, 6.57)
维生素B12(ng/L)	551.63(361.03, 981.50)	547.62(358.75, 1016.73)	677.68(404.65, 1150.90)	677.68(384.77, 1069.51)	687.29(305.46, 1144.62)	648.79(424.54, 1690.57)	316.29(245.81, 502.65)
结合珠蛋白(g/L)	1.83(1.12, 2.64)	1.74(1.08, 2.63)	1.85(1.15, 2.78)	1.76(1.15, 2.57)	1.45(0.66, 2.90)	1.29(0.93, 2.28)	1.64(1.41, 3.45)
铁蛋白(μg/L)	397.65(204.33, 708.26)	386.58(202.65, 715.99)	484.02(191.02, 901.44)	614.35(197.72, 1004.93)	964.50(425.48, 1307.00)	68.58(23.87, 92.82)	187.99(124.84, 1071.75)
转铁蛋白(g/L)	1.45(1.17, 1.72)	1.46(1.17, 1.74)	1.33(1.09, 1.56)	1.25(0.94, 1.55)	1.21(0.90, 1.46)	1.82(1.71, 2.44)	1.61(1.30, 1.72)
可溶性转铁蛋白受体(mg/L)	0.93(0.70, 1.22)	0.92(0.70, 1.22)	0.86(0.63, 1.07)	0.89(0.64, 1.14)	0.76(0.60, 0.90)	1.21(0.98, 1.79)	0.85(0.78, 0.93)
BVAS	16.92±5.88	17.28±5.85	18.11±5.51	20.93±5.37	20.50±5.54	16.18±6.03	20.75±7.74
FFS	2.47±0.96	2.56±0.91	2.66±0.93	3.30±0.72	2.88±0.96	2.36±1.21	2.63±0.92
CCI	3.09±1.36	3.19±1.35	3.43±1.35	4.13±0.97	3.69±0.79	3.45±1.21	3.88±0.64

图2 AAV患者根据贫血原因数量分组的肾脏生存率比较

Fig.2 Comparison of renal survival rates among AAV patients grouped by the number of causes of anemia

图3 HGB与BVAS评分的相关性分析 a.初始HGB与初始BVAS评分的相关性分析;b.终点HGB与终点BVAS评分的相关性分析

Fig.3 Correlation analysis of HGB and BVAS scores a.Correlation analysis between initial HGB and initial BVAS score; b.Correlation analysis of end-point HGB and end-point BVAS score

表4 根据HGB初诊基线和随访终点动态变化分组的AAV患者随访终点特征比较

Tab.4 Comparison of follow-up endpoint characteristics of AAV patients grouped by the dynamic changes of HGB at initial diagnosis baseline and follow-up endpoint

项目	HH( $n$ =16)	HL( $n$ =6)	LH( $n$ =41)	LL( $n$ =28)	$t$ / $Z$ 值	$P$ 值
年龄(岁)	67.00(65.25, 72.25)	67.00(59.75, 71.50)	71.00(65.00, 76.00)	67.00(57.00, 75.00)	3.470	0.325
初诊HGB(g/L)	123.00(118.25, 133.75)	112.00(110.75, 120.50)	91.00(78.50, 99.50)^*△	80.50(68.00, 93.75)^*△	53.621	<0.01
末次HGB(g/L)	142.00±14.50	81.17±21.52^*	127.98±10.28^*△	83.16±19.00^*#	80.015	<0.01
末次CRP(mg/L)	1.30(0.50, 2.97)	71.33(21.90, 94.85)^*	1.10(0.50, 4.17)^△	5.16(0.54, 26.49)	16.984	0.001
末次ESR(mm/h)	12.85(7.10, 15.05)	110.00(104.25, 118.00)^*	15.30(10.10, 22.00)^△	24.00(15.58, 68.90)	19.026	<0.01
末次SCr(μmol/L)	106.00(82.20, 118.90)	361.60(259.08, 907.10)^*	122.20(101.80, 158.75)^△	298.70(185.53, 538.63)^*#	42.187	<0.01
末次eGFR[(ml/(min·1.73 m²)]	61.44(42.42, 65.56)	13.46(7.26, 16.81)^*	37.47(26.29, 49.81)^△	12.94(7.95, 27.65)^*#	43.276	<0.01
末次BUN(mmol/L)	5.48(4.81, 8.51)	25.14(20.56, 49.77)^*	9.76(6.78, 14.21)^*△	24.50(13.33, 39.10)^*#	46.244	<0.01
末次UA(mmol/L)	338.10(258.70, 462.70)	526.85(397.48, 631.75)	393.50(301.20, 478.98)	379.00(251.00, 651.10)	4.979	0.173
末次ALB(g/L)	40.91(40.10, 42.90)	26.50(21.33, 31.28)^*	38.75(36.15, 40.70)^△	32.80(28.90, 36.40)^*#	34.382	<0.01
末次BVAS	2.50(0.00, 3.75)	10.50(7.50, 14.50)^*	2.00(0.00, 5.00)^△	6.00(4.00, 11.75)^*#	34.586	<0.01
末次FFS	1.00(1.00, 1.00)	2.00(1.00, 3.00)	1.00(1.00, 2.00)	1.50(1.00, 2.00)	9.104	0.028

表4 根据HGB初诊基线和随访终点动态变化分组的AAV患者随访终点特征比较

Tab.4 Comparison of follow-up endpoint characteristics of AAV patients grouped by the dynamic changes of HGB at initial diagnosis baseline and follow-up endpoint

项目	HH( $n$ =16)	HL( $n$ =6)	LH( $n$ =41)	LL( $n$ =28)	$t$ / $Z$ 值	$P$ 值
年龄(岁)	67.00(65.25, 72.25)	67.00(59.75, 71.50)	71.00(65.00, 76.00)	67.00(57.00, 75.00)	3.470	0.325
初诊HGB(g/L)	123.00(118.25, 133.75)	112.00(110.75, 120.50)	91.00(78.50, 99.50)^*△	80.50(68.00, 93.75)^*△	53.621	<0.01
末次HGB(g/L)	142.00±14.50	81.17±21.52^*	127.98±10.28^*△	83.16±19.00^*#	80.015	<0.01
末次CRP(mg/L)	1.30(0.50, 2.97)	71.33(21.90, 94.85)^*	1.10(0.50, 4.17)^△	5.16(0.54, 26.49)	16.984	0.001
末次ESR(mm/h)	12.85(7.10, 15.05)	110.00(104.25, 118.00)^*	15.30(10.10, 22.00)^△	24.00(15.58, 68.90)	19.026	<0.01
末次SCr(μmol/L)	106.00(82.20, 118.90)	361.60(259.08, 907.10)^*	122.20(101.80, 158.75)^△	298.70(185.53, 538.63)^*#	42.187	<0.01
末次eGFR[(ml/(min·1.73 m²)]	61.44(42.42, 65.56)	13.46(7.26, 16.81)^*	37.47(26.29, 49.81)^△	12.94(7.95, 27.65)^*#	43.276	<0.01
末次BUN(mmol/L)	5.48(4.81, 8.51)	25.14(20.56, 49.77)^*	9.76(6.78, 14.21)^*△	24.50(13.33, 39.10)^*#	46.244	<0.01
末次UA(mmol/L)	338.10(258.70, 462.70)	526.85(397.48, 631.75)	393.50(301.20, 478.98)	379.00(251.00, 651.10)	4.979	0.173
末次ALB(g/L)	40.91(40.10, 42.90)	26.50(21.33, 31.28)^*	38.75(36.15, 40.70)^△	32.80(28.90, 36.40)^*#	34.382	<0.01
末次BVAS	2.50(0.00, 3.75)	10.50(7.50, 14.50)^*	2.00(0.00, 5.00)^△	6.00(4.00, 11.75)^*#	34.586	<0.01
末次FFS	1.00(1.00, 1.00)	2.00(1.00, 3.00)	1.00(1.00, 2.00)	1.50(1.00, 2.00)	9.104	0.028

图4 AAV患者sIL-6与HGB水平变化的关系

Fig.4 The correlation between the sIL-6 and HGB levels in AAV patients

表5 AAV患者肾脏预后影响因素的单因素COX回归模型分析

Tab.5 Univariate COX regression model analysis of the influencing factors for renal prognosis in AAV patients

项目	回归系数	标准误	Wald χ²值	风险比	95% $C I$	$P$ 值
年龄	-0.008	0.011	0.553	0.992	0.970~1.014	0.457
初诊HGB(g/L)	-0.025	0.008	9.874	0.975	0.960~0.991	0.002
CRP(mg/L)	-0.002	0.003	0.455	0.998	0.992~1.004	0.500
ESR(mm/h)	0.003	0.004	0.623	1.003	0.996~1.010	0.430
SCr(μmol/L)	0.001	0	12.405	1.001	1.001~1.002	<0.01
eGFR[ml/(min·1.73 m²)]	-0.031	0.009	11.497	0.97	0.952~0.987	0.001
BUN(mmol/L)	0.030	0.008	14.352	1.031	1.015~1.047	<0.01
UA(mmol/L)	0.003	0.001	16.272	1.003	1.002~1.005	<0.01
ALB(g/L)	-0.048	0.026	3.345	0.953	0.906~1.003	0.067
DD(μg/L)	0	0	4.541	1.000	1.000~1.000	0.033
24 h尿蛋白定量(g/24 h)	0.246	0.077	10.221	1.279	1.100~1.488	0.001
PCT(μg/L)	-0.079	0.114	0.483	0.924	0.740~1.154	0.487
CD4绝对计数(cells/μl)	-0.002	0.001	4.534	0.998	0.996~1.000	0.033
BNP(ng/L)	0	0	3.301	1.000	1.000~1.001	0.069
叶酸( μg/L)	-0.012	0.032	0.132	0.988	0.929~1.052	0.716
维生素B12(ng/L)	0	0	0.119	1.000	0.999~1.001	0.730
结合珠蛋白(g/L)	-0.190	0.182	1.087	0.827	0.579~1.182	0.297
铁蛋白(μg/L)	0	0	0.158	1.000	0.999~1.001	0.691
转铁蛋白(g/L)	0.192	0.427	0.203	1.212	0.525~2.797	0.653
可溶性转铁蛋白受体(mg/L)	0.216	0.315	0.472	1.241	0.670~2.301	0.492
BVAS	0.029	0.025	1.267	1.029	0.979~1.082	0.260
FFS	0.285	0.157	3.306	1.33	0.978~1.810	0.069
CCI	0.320	0.104	9.393	1.377	1.122~1.689	0.002

表5 AAV患者肾脏预后影响因素的单因素COX回归模型分析

Tab.5 Univariate COX regression model analysis of the influencing factors for renal prognosis in AAV patients

项目	回归系数	标准误	Wald χ²值	风险比	95% $C I$	$P$ 值
年龄	-0.008	0.011	0.553	0.992	0.970~1.014	0.457
初诊HGB(g/L)	-0.025	0.008	9.874	0.975	0.960~0.991	0.002
CRP(mg/L)	-0.002	0.003	0.455	0.998	0.992~1.004	0.500
ESR(mm/h)	0.003	0.004	0.623	1.003	0.996~1.010	0.430
SCr(μmol/L)	0.001	0	12.405	1.001	1.001~1.002	<0.01
eGFR[ml/(min·1.73 m²)]	-0.031	0.009	11.497	0.97	0.952~0.987	0.001
BUN(mmol/L)	0.030	0.008	14.352	1.031	1.015~1.047	<0.01
UA(mmol/L)	0.003	0.001	16.272	1.003	1.002~1.005	<0.01
ALB(g/L)	-0.048	0.026	3.345	0.953	0.906~1.003	0.067
DD(μg/L)	0	0	4.541	1.000	1.000~1.000	0.033
24 h尿蛋白定量(g/24 h)	0.246	0.077	10.221	1.279	1.100~1.488	0.001
PCT(μg/L)	-0.079	0.114	0.483	0.924	0.740~1.154	0.487
CD4绝对计数(cells/μl)	-0.002	0.001	4.534	0.998	0.996~1.000	0.033
BNP(ng/L)	0	0	3.301	1.000	1.000~1.001	0.069
叶酸( μg/L)	-0.012	0.032	0.132	0.988	0.929~1.052	0.716
维生素B12(ng/L)	0	0	0.119	1.000	0.999~1.001	0.730
结合珠蛋白(g/L)	-0.190	0.182	1.087	0.827	0.579~1.182	0.297
铁蛋白(μg/L)	0	0	0.158	1.000	0.999~1.001	0.691
转铁蛋白(g/L)	0.192	0.427	0.203	1.212	0.525~2.797	0.653
可溶性转铁蛋白受体(mg/L)	0.216	0.315	0.472	1.241	0.670~2.301	0.492
BVAS	0.029	0.025	1.267	1.029	0.979~1.082	0.260
FFS	0.285	0.157	3.306	1.33	0.978~1.810	0.069
CCI	0.320	0.104	9.393	1.377	1.122~1.689	0.002

表6 AAV患者肾脏预后影响因素的多因素COX回归模型分析

Tab.6 Multivariate COX regression model analysis of the influencing factors for renal prognosis in AAV patients

项目	回归系数	标准误	Wald χ²值	风险比	95% $C I$	$P$ 值
年龄	-0.069	0.032	4.697	0.934	0.877~0.993	0.030
初诊HGB(g/L)	-0.046	0.028	2.781	0.955	0.905~1.008	0.095
SCr(μmol/L)	0.004	0.001	8.070	1.004	1.001~1.007	0.005
eGFR[ml/(min·1.73 m²)]	0.024	0.031	0.573	1.024	0.963~1.089	0.449
DD(μg/L)	0	0	2.090	1.000	0.999~1.000	0.148
24 h尿蛋白定量(g/24 h)	0.412	0.181	5.169	1.510	1.059~2.154	0.023
CD4绝对计数(cells/μl)	0	0.001	0.026	1.000	0.998~1.002	0.871
CCI	-0.027	0.264	0.011	0.973	0.580~1.633	0.917

表6 AAV患者肾脏预后影响因素的多因素COX回归模型分析

Tab.6 Multivariate COX regression model analysis of the influencing factors for renal prognosis in AAV patients

项目	回归系数	标准误	Wald χ²值	风险比	95% $C I$	$P$ 值
年龄	-0.069	0.032	4.697	0.934	0.877~0.993	0.030
初诊HGB(g/L)	-0.046	0.028	2.781	0.955	0.905~1.008	0.095
SCr(μmol/L)	0.004	0.001	8.070	1.004	1.001~1.007	0.005
eGFR[ml/(min·1.73 m²)]	0.024	0.031	0.573	1.024	0.963~1.089	0.449
DD(μg/L)	0	0	2.090	1.000	0.999~1.000	0.148
24 h尿蛋白定量(g/24 h)	0.412	0.181	5.169	1.510	1.059~2.154	0.023
CD4绝对计数(cells/μl)	0	0.001	0.026	1.000	0.998~1.002	0.871
CCI	-0.027	0.264	0.011	0.973	0.580~1.633	0.917

图5 依据HGB偏移分组的肾脏生存率和全因死亡率比较 a.根据初始及随访终点血红蛋白分组的肾脏生存率比较; b.根据初始及随访终点血红蛋白分组的全因死亡率比较

Fig.5 Comparison of renal survival rate and all-cause mortality based on HGB deviation grouping a.Comparison of renal survival rates based on HGB groups at the initial and follow-up endpoints;b.Comparison of all-cause mortality based on HGB groups at the initial and follow-up endpoints

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