The role of anemia in evaluating disease severity and prognosis of ANCA-associated vasculitis

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

Abstract

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

CLC Number:

R543

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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URL: https://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2025.09.005

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

Figures/Tables 11

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]。

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References 29

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