A preliminary nomogram model for predicting relapse of patients with primary membranous nephropathy

Figures & data

Table 1. Comparison of characteristics between the development cohort and the validation cohort.

Characteristic	Primary group (n = 400)	Development group (n = 280)	Validation group (n = 120)	P-value
Age (years)	49.00 (39.00, 58.00)	49.00 (38.25, 58.00)	49.00 (40.00, 58.00)	0.935
Gender (male,n%)	249 (62.25)	184 (65.71)	65 (54.17)	0.029
Hypertension,n (%)	120 (30.00)	83 (29.64)	37 (30.83)	0.812
Diabetes mellitus,n (%)	29 (7.25)	16 (5.71)	13 (10.83)	0.199
Hyperuricemia,n (%)	166 (41.50)	122 (43.57)	44 (36.67)	0.199
Smoking,n (%)	101 (25.25)	75 (26.79)	26 (21.67)	0.280
PLA2R Abs (RU/ml)	15.68 (1.44, 89.02)	16.60 (1.44, 93.79)	11.25 (1.38, 83.70)	0.793
UTP (g/24h)	4.02 (2.25, 6.35)	4.18 (2.47, 6.62)	3.60 (2.02, 6.30)	0.134
URBC(/ul)	14.40 (3.63, 41.18)	13.86 (3.96, 42.75)	15.05 (3.30, 40.10)	0.701
Eosinophil count (*10^9/L)	0.10 (0.05, 0.17)	0.10 (0.06, 0.17)	0.10 (0.05, 0.18)	0.842
Hemoglobin (g/L)	138.00 (127.00, 149.00)	139.50 (128.00, 149.00)	135.00 (127.00, 147.00)	0.107
CRP (mg/L)	1.66 (0.96, 2.30)	1.66 (1.08, 2.42)	1.60 (0.86, 1.81)	0.068
Total protein (g/L)	47.90 (42.01, 53.63)	47.80 (41.75, 52.81)	48.16 (42.47, 55.26)	0.254
Albumin (g/L)	25.32 (20.95, 29.83)	25.05 (20.76, 29.83)	26.10 (21.83, 29.83)	0.246
Blood urea nitrogen (mmol/L)	5.16 (4.20, 6.15)	5.12 (4.23, 6.26)	5.17 (4.16, 6.05)	0.815
Serum creatinine (μmol/L)	65.00 (52.00, 77.08)	66.00 (52.25, 77.90)	63.00 (52.00, 75.23)	0.481
eGFR (ml/min/1.73m^2)	105.46 (97.41, 114.13)	105.82 (97.68, 115.39)	104.92 (96.25, 113.27)	0.442
Triglyceride (mmol/L)	1.89 (1.30, 2.66)	1.92 (1.30, 2.71)	1.87 (1.27, 2.61)	0.659
Total cholesterol (mmol/L)	7.26 (5.98, 9.12)	7.14 (6.00, 9.29)	7.36 (5.88, 8.90)	0.805
Low-density lipoprotein cholesterol (mmol/L)	4.62 (3.51, 6.00)	4.60 (3.60, 6.09)	4.73 (3.27, 5.82)	0.449
Serum-IgA (g/L)	2.08 (1.60, 2.75)	2.13 (1.59, 2.80)	2.02 (1.62, 2.62)	0.648
Serum-IgM (g/L)	0.98 (0.71, 1.36)	0.99 (0.73, 1.33)	0.90 (0.68, 1.41)	0.838
Serum-IgG (g/L)	5.93 (4.41, 7.87)	5.85 (4.46, 7.63)	6.21 (4.30, 8.39)	0.208
Serum-IgE (IU/ml)	79.62 (33.24, 161.78)	81.78 (34.62, 163.90)	70.70 (29.80, 154.13)	0.312
Serum-C3 (g/L)	1.14 (0.99, 1.28)	1.15 (0.99, 1.29)	1.14 (0.99, 1.28)	0.935
Serum-C4 (g/L)	0.27 (0.22, 0.32)	0.27 (0.22, 0.32)	0.26 (0.22, 0.31)	0.329
Pathological feature
Churg’s stage				0.266
I, n (%)	46 (11.50)	29 (10.36)	17 (14.17)
II, n (%)	346 (86.50)	245 (87.50)	101 (84.17)
III, n (%)	8 (2.00)	6 (2.15)	2 (1.67)
IgG deposit				0.096
-, n (%)	1 (0.25)	1 (0.36)
1+, n (%)	20 (5.00)	13 (4.64)	7 (5.83)
2+, n (%)	176 (44.00)	116 (41.43)	60 (50.00)
3+, n (%)	203 (50.75)	150 (53.57)	53 (44.17)
C3 deposit				0.252
-, n (%)	129 (32.25)	87 (31.07)	42 (35.00)
1+, n (%)	222 (55.50)	155 (55.36)	67 (55.83)
2+, n (%)	49 (12.25)	38 (13.57)	11 (9.17)
C1q deposit				0.509
-, n (%)	276 (69.00)	196 (70.00)	80 (66.67)
1+, n (%)	124 (31.00)	84 (30.00)	40 (33.33)
PLA2R Ag				0.576
-, n (%)	49 (12.25)	30 (10.71)	19 (15.83)
1+, n (%)	109 (27.25)	80 (28.57)	29 (24.17)
2+, n (%)	240 (60.00)	168 (60.00)	72 (60.00)
3+, n (%)	2 (0.50)	2 (0.71)
Glomerular IgG deposits
IgG1, n (%)	342 (85.50)	236 (84.29)	106 (88.33)	0.292
IgG2, n (%)	302 (75.50)	213 (76.07)	89 (74.17)	0.685
IgG3, n (%)	142 (35.50)	101 (36.07)	41 (34.17)	0.715
IgG4, n (%)	373 (93.25)	263 (93.93)	110 (91.67)	0.409
ACEI/ARB	377 (94.25)	258 (94.85)	119 (92.97)	0.450
Therapeutic regimen				0.272
CTX + GCs, n (%)	93 (23.25)	58 (20.71)	35 (29.17)
CNIs ± GCs, n (%)	164 (41.00)	120 (42.86)	44 (36.67)
CTX/CNIs ± GCs, n (%)	57 (14.25)	42 (15.00)	15 (12.50)
Others, n (%)	86 (21.50)	60 (21.43)	26 (21.67)
Complete remission, n (%)	280 (70.00)	194 (69.29)	86 (71.67)	0.634
Follow-up time (months)	16.00 (10.00, 28.00)	16.00 (10.00, 27.75)	17.00 (11.00, 28.75)	0.412

The quantitative variable was displayed as median and interquartile ranges; categorical variable and rank variable were displayed as quantities and percentages.

BMI: body mass index; MAP: mean arterial pressure; PLA2R Abs: anti-phospholipase A2 receptor antibodies; UTP: 24-h urinary protein quantity; URBC: urinary red blood cell counts; CRP: C-reactive protein; GFR: estimated glomerular filtration rate; PLA2R Ag: glomerular phospholipase A2 receptor antigen; CTX + GCs: cyclophosphamide-glucocorticoids; CNIs ± GCs: calcineurin inhibitors with or without glucocorticoids; CTX/CNIs ± GCs: alternatively treat with CTX + GCs and CNIs ± GCs in any order.

Table 2. Characteristics of patients between non-relapse group and relapse group in development group.

Characteristic	Non-relapse group (n = 185)	Relapse group (n = 95)	P-value
Age (years)	50.00 (42.00, 58.00)	48.00 (36.00, 58.00)	0.174
Gender (male)	112 (60.54)	72 (75.79)	0.011
Hypertension, n (%)	59 (31.89)	24 (25.26)	0.250
Diabetes mellitus, n (%)	11 (5.95)	5 (5.26)	0.816
Hyperuricemia, n (%)	57 (30.81)	65 (68.42)	<0.001
Smoking, n (%)	44 (23.78)	31 (32.63)	0.113
PLA2R Abs (RU/ml)	18.19 (1.52, 98.47)	5.95 (1.43, 84.61)	0.390
UTP (g/24h)	4.16 (2.43, 6.75)	4.28 (2.70, 6.18)	0.815
URBC (/ul)	11.88 (2.64, 35.51)	23.10 (7.26, 53.60)	0.003
Eosinophil count (*10^9/L)	0.12 (0.07, 0.19)	0.09 (0.04, 0.15)	0.012
Hemoglobin (g/L)	139.00 (127.0, 150.00)	140.00 (129.00, 149.00)	0.858
CRP (mg/L)	1.66 (0.93, 1.66)	2.42 (1.30, 3.42)	<0.001
Total protein (g/L)	47.90 (41.75, 53.73)	46.82 (41.20, 51.82)	0.571
Albumin (g/L)	25.60 (21.08, 29.96)	24.30 (20.06, 28.72)	0.285
Serum creatinine (μmol/L)	63.00 (50.20, 74.50)	70.90 (59.00, 82.00)	0.001
eGFR (ml/min/1.73m^2)	106.55 (97.56, 116.86)	104.67 (97.71, 113.37)	0.359
Triglyceride (mmol/L)	1.91 (1.34, 2.66)	1.93 (1.20, 2.82)	0.449
Total cholesterol (mmol/L)	7.25 (5.90, 9.31)	7.10 (6.17, 9.29)	0.859
Low density lipoprotein cholesterol (mmol/L)	4.61 (3.33, 6.16)	4.55 (3.72, 5.90)	0.869
Serum-IgA (g/L)	2.19 (1.60, 2.92)	2.00 (1.56, 2.55)	0.247
Serum-IgM (g/L)	0.97 (0.74, 1.29)	1.00 (0.72, 1.52)	0.225
Serum-IgG (g/L)	5.78 (4.54, 7.26)	6.23 (3.73, 8.06)	0.696
Serum-IgE (IU/ml)	66.38 (31.99, 152.77)	110.20 (41.60, 167.32)	0.023
Serum-C3 (g/L)	1.14 (0.98, 1.28)	1.16 (0.99, 1.33)	0.488
Serum-C4 (g/L)	0.27 (0.23, 0.33)	0.268 (0.22, 0.32)	0.731
Pathological feature
Churg’s stage			0.126
I, n (%)	16 (8.65)	13 (13.68)
II, n (%)	164 (88.65)	81 (85.26)
III, n (%)	5 (2.70)	1 (1.05)
C3 deposit			0.447
-, n (%)	61 (32.97)	26 (27.37)
1+, n (%)	99 (53.51)	56 (58.95)
2+, n (%)	25 (13.51)	13 (13.68)
C1q deposit			0.130
-, n (%)	124 (67.03)	72 (75.79)
1+, n (%)	61 (32.97)	23 (24.21)
PLA2R Ag			0.187
-, n (%)	23 (12.43)	7 (7.37)
1+, n (%)	54 (29.19)	26 (27.37)
2+, n (%)	107 (57.84)	61 (64.21)
3+, n (%)	1 (0.54)	1 (1.05)
Glomerular IgG deposits
IgG1, n (%)	155 (83.78)	81 (85.26)	0.747
IgG2, n (%)	130 (70.27)	83 (87.37)	0.001
IgG3, n (%)	63 (34.05)	38 (40.00)	0.327
IgG4, n (%)	175 (94.59)	88 (92.63)	0.515
ACEI/ARB	175 (94.59)	89 (93.68)	0.756
Therapeutic regimen			0.256
CTX + GCs, n (%)	49 (26.49)	9 (9.47)
CNIs ± GCs, n (%)	65 (35.14)	55 (57.89)	<0.001*
CTX/CNIs ± GCs, n (%)	32 (17.30)	10 (10.53)	0.297*
Others, n (%)	39 (21.08)	21 (22.11)	0.015*
Complete remission, n (%)	136 (73.51)	58 (61.05)	0.032
Follow-up time (months)	20.00 (12.00, 31.25)	12.00 (8.00, 22.00)	<0.001

* Results of pairwise comparisons were performed with CTX + GCs as the reference category. Adjusted significance level α’=α/3, α’=0.05/3 = 0.017.

Table 3. Univariate and Multivariate Cox regression analysis for predictors of relapse.

Characteristic	Univariate Cox regression analysis		Multivariate Cox regression analysis
	HR (95%CI)	P-value	HR (95%CI)	P-value
Age	0.991 (0.975, 1.008)	0.298	–	–
Gender (male)	1.561 (0.975, 2.498)	0.064	1.447 (0.865, 2.419)	0.159
Hyperuricemia	3.441 (2.220, 5.334)	<0.001	2.938 (1.875, 4.605)	<0.001
PLA2R Abs	1.000 (0.999, 1.001)	0.903	1.000 (0.999, 1.001)	0.414
URBC	1.003 (1.001, 1.005)	0.002	1.002 (0.999, 1.004)	0.146
UTP	0.999 (0.945, 1.056)	0.971	0.972 (0.908, 1.040)	0.411
CRP	1.164 (1.110, 1.221)	<0.001	1.147 (1.086, 1.211)	<0.001
Serum creatinine	1.027 (1.014, 1.039)	<0.001	–
eGFR	0.986 (0.972, 1.001)	0.070	0.997 (0.975, 1.020)	0.814
Eos	0.216 (0.023, 1.994)	0.176	0.229 (0.019, 2.809)	0.249
IgE	1.000 (0.999, 1.001)	0.412	1.001 (0.999, 1.002)	0.343
Pathological feature
PLA2R Ag		0.246		0.322
-	1		1
1+	0.515 (0.063, 4.219)	0.536	1.865 (0.752, 4.632)	0.178
2+	1.247 (0.168, 9.244)	0.829	1.234 (0.532, 2.860)	0.624
3+	1.049 (0.145, 7.582)	0.962	0.723 (0.087, 6.030)	0.764
Therapeutic regimen		0.000		0.013
CTX + GCs	1		1
CNIs ± GCs	4.838 (2.373, 9.866)	<0.001	2.845 (1.361, 5.946)	0.015
CTX/CNIs ± GCs	1.552 (0.616, 3.915)	0.351	1.269 (0.500, 3.222)	0.617
Others	3.243 (1.482, 7.095)	0.003	2.182 (0.967, 4.923)	0.060
Complete remission	0.359 (0.233, 0.553)	<0.001	0.420 (0.270, 0.655)	<0.001

Figure 1. Flow diagram of the whole study.

Figure 2. Nomogram for the prediction for IMN reccurence. HUA: Hyperuricemia; CRP: C-reactive protein; CR: complete remisssion.

Figure 3. Calibration plots in the development and validation group of the nomogram. Calibration at 1 year in the development group (A) and validation group(B), Calibration at 2 years in the development group (C) and validation group(D), Calibration at 3 years in the development group (E) and validation group (F).