Glomerular C4 deposition and glomerulosclerosis predict worse renal outcomes in Chinese patients with IgA nephropathy

Figures & data

Table 1. Baseline clinical characteristics and histopathologic features of 642 IgAN patients at the time of renal biopsy.

Characteristics	Total (N = 642)	C4 negative group (n = 601)	C4 positive group (n = 41)	p-value
Male (n, %)	281 (43.77%)	267 (44.43%)	14 (34.15%)	0.20
Age (years)	33.23 (26.83, 42.50)	33.23 (26.53, 42.39)	34.00 (29.00, 44.92)	0.17
MAP (mmHg)	97.00 (89.00, 108.00)	97.00 (88.67, 107.67)	101.50 (91.17, 117.83)	0.15
Hypertension (n, %)	222 (34.60%)	205 (34.10%)	17 (41.50%)	0.29
Hemoglobin (g/L)	133.00 (122.00, 148.00)	133.00 (122.00, 149.00)	133.00 (122.00, 142.00)	0.54
Albumin (g/L)	39.40 (35.50, 42.80)	39.50 (35.70, 43.00)	36.30 (32.10, 40.60)	<0.01
Serum creatinine (µmol/L)	86.35 (67.00, 118.10)	86.60 (67.00, 117.20)	82.84 (63.80, 137.00)	0.97
eGFR (ml/min/1.73m^2)	85.84 (60.90, 110.30)	85.87 (61.59, 109.91)	85.05 (48.61, 110.50)	0.46
Uric acid (µmol/L)	366.35 (300.70, 442.00)	365.70 (300.70, 442.00)	385.20 (303.30, 426.70)	0.93
Triglyceride (mmol/L)	1.52 (1.05, 2.27)	1.51 (1.04, 2.24)	1.88 (1.18, 3.20)	0.07
Cholesterol (mmol/L)	4.79 (4.07, 5.72)	4.77 (4.07, 5.69)	4.97 (4.38, 5.92)	0.21
24-h urinary protein (g/day)	1.43 (0.70, 2.95)	1.39 (0.69, 2.87)	1.99 (1.10, 4.47)	0.01
Serum C3 (g/L)	0.88 (0.78, 1.01)	0.88 (0.78, 1.01)	0.92 (0.77, 1.02)	0.38
Serum C4 (g/L)	0.21 (0.17, 0.25)	0.21 (0.17, 0.25)	0.21 (0.17, 0.27)	0.68
ACEI/ARB (n, %)	433 (67.45%)	406 (67.55%)	27 (65.85%)	0.81
Immunosuppression therapy (n, %)	378 (58.88%)	355 (59.07%)	23 (56.10%)	0.70
Median follow-up period (months)	43.18 (31.13, 59.23)	43.23 (31.63, 59.73)	39.43 (26.00, 56.17)	0.21
Oxford classification
Mesangial hypercellularity (M1)	390 (60.75%)	359 (59.73%)	31 (75.61%)	0.04
Endocapillary hypercellularity (E1)	46 (7.17%)	39 (6.49%)	7 (17.07%)	0.01
Segmental glomerulosclerosis (S1)	330 (51.40%)	313 (52.08%)	17 (41.46%)	0.19
Tubular atrophy/interstitial fibrosis				0.47
T1	115 (17.91%)	106 (17.64%)	9 (21.95%)
T2	42 (6.54%)	41 (6.82%)	1 (2.44%)
Cellular or fibrocellular crescents				0.09
C1	134 (20.87%)	124 (20.63%)	10 (24.39%)
C2	16 (2.49%)	13 (2.16%)	3 (7.32%)
Global sclerosis				0.28
G1	140 (20.81%)	133 (22.13%)	7 (17.07%)
G2	48 (7.48%)	47 (7.82%)	1 (2.44%)
Immune complex deposition
IgG	77 (11.99%)	63 (10.48%)	14 (34.15%)	<0.01
IgM	305 (47.51%)	267 (44.43%)	38 (92.68%)	<0.01
C3	506 (78.82%)	470 (78.20%)	36 (87.80%)	0.15
C1q	80 (12.46%)	55 (9.15%)	25 (60.96%)	<0.01

Figure 1. Kaplan–Meier analysis for the survival probability of the composite endpoint by C4 groups.

Figure 2. Kaplan–Meier analysis for the survival probability of the composite endpoint by different G-scores.

Figure 3. Kaplan–Meier analysis for the survival probability of the composite endpoint by different C-scores.

Table 2. Univariate Cox regression analyses for the risk factors of renal survival.

Variable	Univariate analysis	p-value
	HR (95% CI)
Gender (male vs. female)	1.58 (1.03, 2.48)	0.04
Age (years)	1.00 (0.98, 1.02)	0.74
Hypertension	2.14 (1.39, 3.32)	<0.01
Hemoglobin (g/L)	0.99 (0.98, 1.00)	0.04
Albumin (g/L)	0.95 (0.92, 0.98)	<0.01
Serum creatinine (µmol/L)	1.01 (1.01, 1.02)	<0.01
eGFR (ml/min/1.73m^2)	0.97 (0.96, 0.98)	<0.01
Uric acid (µmol/L)	1.01 (1.00, 1.01)	<0.01
Triglyceride (mmol/L)	1.24 (1.13, 1.36)	<0.01
Cholesterol (mmol/L)	1.09 (0.97, 1.24)	0.16
24-h urinary protein (g/day)	1.08 (1.05, 1.12)	<0.01
Serum C3 (g/L)	0.20 (0.05, 0.74)	0.02
Serum C4 (g/L)	10.58 (1.15, 97.60)	0.04
Serum C3/C4	0.66 (0.51, 0.85)	<0.01
Immunosuppression therapy	1.30 (0.82, 2.07)	0.26
Oxford classification
M1	1.65 (1.02, 2.68)	0.04
E1	0.99 (0.45, 2.16)	0.98
S1	1.28 (0.82, 2.00)	0.27
T1 vs. T0	3.00 (1.82, 4.96)	<0.01
T2 vs. T0	6.34 (3.60, 11.15)	<0.01
C1 vs. C0	1.72 (1.06, 2.79)	0.03
C2 vs. C0	2.21 (0.87, 5.61)	0.10
Global sclerosis
G1 vs. G0	2.78 (1.68, 4.59)	<0.01
G2 vs. G0	6.35 (3.63, 11.13)	<0.01
Immune complex deposition
C3 (+ vs. −)	1.47 (0.82, 2.61)	0.19
C4 (+ vs. −)	2.13 (1.07, 4.27)	0.03
C1q (+ vs. −)	1.78 (1.05, 3.01)	0.03

HR: hazard ratio; CI: confidence interval.

Table 3. Multivariate Cox regression analyses for the risk factors of renal survival.

Variable	Multivariate analysis	p-value
	HR (95% CI)
Gender (male vs. female)	1.80 (1.10, 2.97)	0.02
Serum creatinine (µmol/L)	1.01 (1.00, 1.01)	<0.01
Triglyceride (mmol/L)	1.17 (1.01, 1.35)	0.04
24-h urinary protein (g/day)	1.07 (1.01, 1.13)	0.02
Serum C3 (g/L)	0.05 (0.01, 0.25)	<0.01
Serum C4 (g/L)	99.59 (8.69, 1140.89)	<0.01
Global sclerosis
G1 vs. G0	1.90 (1.02, 3.52)	0.04
G2 vs. G0	3.72 (1.98, 7.00)	<0.01
Immune complex deposition
C4 (+ vs. −)	3.22 (1.51, 6.87)	<0.01

HR: hazard ratio; CI: confidence interval.