The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy

Figures & data

Table 1. Comparison of clinical and coagulation features in patients with IMN and patients with MCD.

	IMN(n = 168)	MCD(n = 36)	p value
Sex(male, %)	106(63.1%)	17(47.2%)	0.077
Age(years)	51(37,57.75)	41.5(24,56)	0.018
Alb(g/L)	30.96 ± 7.18	24.1 ± 4.02	<0.001
SCR(mg/dL)	0.84(0.68,1.01)	0.84(0.7,1.03)	0.708
BUN(mg/dL)	14.9(12.06,18.57)	15.49(11.64,22.18)	0.491
UA(μmol/L)	373.99 ± 86.17	361.36 ± 112.07	0.452
TC(mmol/L)	6.87(5.55,8.69)	10.53(8.86,13.89)	<0.001
TG(mmol/L)	2.04(1.29,3.3)	2.47(1.64,3.67)	0.087
HDL(mmol/L)	1.24 ± 0.4	1.78 ± 0.57	<0.001
LDL(mmol/L)	3.95(2.63,5.2)	6.06(5.27,8.98)	<0.001
eGFR(mL/min/1.73m²)	101.5(82.25,115.75)	103(82.5,118.5)	0.871
Urinary protein (g/24h)	4.11(2.51,8.02)	8.91(5.99,16.2)	<0.001
PLT(×10^9/L)	250.66 ± 67.33	291.31 ± 76.62	0.002
HCT	0.42 ± 0.05	0.45 ± 0.04	0.017
Hb (g/L)	137.67 ± 18.01	148.50 ± 17.30	0.001
PT(s)	10.61 ± 0.72	10.73 ± 0.71	0.344
APTT(s)	24.95(23.6,26)	26.5(24.8,29.33)	<0.001
TT(s)	16.9(16.5,17.48)	17.6(16.93,18.1)	<0.001
Fib(g/L)	4.33(3.18,4.84)	5.96(4.95,6.89)	<0.001
D-dimer (mg/L)	0.1(0.1,0.2)	0.1(0.1,0.4)	0.155
R(min)	6.84 ± 1.33	7.45 ± 1.64	0.017
K(min)	1.3(1.2,1.7)	1.4(1.2,1.78)	0.584
CI	0.97 ± 1.58	0.82 ± 1.86	0.613
α-angle (°)	70.25(65.75,73.25)	70.6(66,72.83)	0.943
MA(mm)	69.33 ± 5.09	71.73 ± 4.36	0.009

IMN: idiopathic membranous nephropathy; MCD: minimal change disease; Alb: serum albumin; SCR: serum creatinine; BUN: blood urea nitrogen; UA: uric acid; TC: total cholesterol; TG: triacylglycerol; HDL: high-density lipoproteins; LDL: low-density lipoproteins; eGFR: estimated glomerular filtration rate; PLT: platelet count; HCT: hematocrit; Hb: hemoglobin; PT: prothrombin time; APTT: activated partial thromboplastin time; TT: thrombin time; Fib: fibrinogen.

Figure 1. Biopsy finding of patients with IMN who were glomerular PLA2R staining-positive (GAg+). immunofluorescence includes staining for PLA2R, IgG and C3.

Table 2. Comparison of clinical and coagulation features in patients with IMN who were GAg + and patients with IMN who were GAg.

	GAg + IMN(n = 139)	GAg- IMN(n = 29)	p Value
Sex(male, %)	90(64.8%)	16(55.2%)	0.331
Age(years)	52(38,57)	42(33,62.5)	0.381
Alb(g/L)	30.19 ± 6.19	34.63 ± 10.06	0.029
SCR(mg/dL)	0.84(0.69,1)	0.83(0.62,1.05)	0.882
BUN(mg/dL)	14.99(12.12,18.36)	13.79(11.42,21.99)	0.946
UA(μmol/L)	361(316,451)	338(273,440.5)	0.228
TC(mmol/L)	6.92(5.68,8.67)	6.66(4.78,8.88)	0.574
TG(mmol/L)	2.12(1.34,3.39)	1.46(1.11,2.66)	0.046
HDL(mmol/L)	1.16(0.96,1.47)	1.1(0.85,1.44)	0.247
LDL(mmol/L)	3.96(2.68,5.13)	3.95(2.54,5.53)	0.702
eGFR(mL/min/1.73m²)	101(85,114)	113(75.5,120.5)	0.785
Urinary protein (g/24h)	4.31(2.63,8.31)	3.44(1.55,7.73)	0.195
PLT(×10^9/L)	250.97 ± 67.33	249.17 ± 68.48	0.896
HCT	0.43 ± 0.05	0.42 ± 0.06	0.525
Hb (g/L)	137.43 ± 17.50	138.79 ± 20.60	0.712
PT(s)	10.51 ± 0.68	11.06 ± 0.75	<0.001
APTT(s)	24.68 ± 1.90	26.19 ± 1.84	<0.001
TT(s)	16.99 ± 0.80	16.89 ± 0.83	0.51
Fib(g/L)	4.23(3.21,4.84)	4.34(2.98,5.32)	0.719
D-dimer (mg/L)	0.1(0.1,0.13)	0.1(0.1,0.29)	0.199
R(min)	6.74 ± 1.33	7.34 ± 1.23	0.025
K(min)	1.3(1.1,1.7)	1.5(1.25,1.9)	0.11
CI	1.09 ± 1.58	0.40 ± 1.48	0.031
α-angle (°)	70.4(66.4,73.6)	68.1(63.4,71.5)	0.072
MA(mm)	69.44 ± 5.03	68.84 ± 5.46	0.568

IMN: idiopathic membranous nephropathy; GAg: glomerular phospholipase A2 receptor antigen; Alb: serum albumin; SCR: serum creatinine; BUN: blood urea nitrogen; UA: uric acid; TC: total cholesterol; TG: triacylglycerol; HDL: high-density lipoproteins; LDL: low-density lipoproteins; eGFR: estimated glomerular filtration rate; PLT: platelet count; HCT: hematocrit; Hb: hemoglobin; PT: prothrombin time; APTT: activated partial thromboplastin time; TT: thrombin time; Fib: fibrinogen.

Table 3. Comparison of clinical and coagulation features in patients with IMN who were SAb+/GAg + and patients with IMN who were SAb-/GAg+.

	SAb+/GAg+ (n = 85)	SAb-/GAg+ (n = 54)	p Value
Sex(male, %)	55(64.7%)	35(64.8%)	0.99
Age(years)	53(39.5,57.5)	49(35.75,56.25)	0.191
Alb(g/L)	29.42 ± 6.02	31.40 ± 6.33	0.065
SCR(mg/dL)	0.86(0.7,1.05)	0.81(0.68,0.93)	0.103
BUN(mg/dL)	15.9(12.3,18.9)	14.48(11.92,17.26)	0.109
UA(μmol/L)	361(311.5,448.5)	395.5(319.75,453.5)	0.718
TC(mmol/L)	7.65(6.17,10.1)	6.05(4.88,7.25)	<0.001
TG(mmol/L)	2.15(1.42,3.6)	2.08(1.11,3.15)	0.121
HDL(mmol/L)	1.24(0.99,1.53)	1.06(0.88,1.4)	0.012
LDL(mmol/L)	4.37(3.24,6.4)	3.14(2.36,4.28)	<0.001
eGFR(mL/min/1.73m²)	99(81.5,111)	106(89.75,120.25)	0.013
Urinary protein (g/24h)	5.96(3.23,10.93)	2.97(2.22,4.64)	<0.001
PLT(×10^9/L)	262.86 ± 69.00	232.26 ± 60.62	0.009
HCT	0.42 ± 0.05	0.43 ± 0.05	0.438
Hb (g/L)	139.52 ± 17.60	134.15 ± 17.00	0.078
PT(s)	10.44 ± 0.64	10.62 ± 0.73	0.134
APTT(s)	24.63 ± 1.73	24.77 ± 2.16	0.66
TT(s)	17.1(16.5,17.5)	16.9(16.4,17.4)	0.296
Fib(g/L)	4.5(3.83,5.14)	3.39(2.79,4.46)	<0.001
D-dimer (mg/L)	0.1(0.1,0.23)	0.1(0.1,0.1)	0.102
R(min)	6.7(6.2,7.75)	6.6(5.28,7.53)	0.087
K(min)	1.3(1.1,1.6)	1.25(1.1,1.8)	0.744
CI	1.08 ± 1.62	1.10 ± 1.53	0.951
α-angle (°)	70.5(66.75,73.75)	70(65.05,72.7)	0.336
MA(mm)	70.38 ± 4.90	67.95 ± 4.90	0.005

IMN: idiopathic membranous nephropathy; SAb: serum anti-phospholipase A2 receptor antibody; GAg: glomerular phospholipase A2 receptor antigen; Alb: serum albumin; SCR: serum creatinine; BUN: blood urea nitrogen; UA: uric acid; TC: total cholesterol; TG: triacylglycerol; HDL: high-density lipoproteins; LDL: low-density lipoproteins; eGFR: estimated glomerular filtration rate; PLT: platelet count; HCT: hematocrit; Hb: hemoglobin; PT: prothrombin time; APTT: activated partial thromboplastin time; TT: thrombin time; Fib: fibrinogen.

Figure 2. The scatter plots indicate the correlation between anti-PLA2R antibodies and the coagulation indices in patients with IMN who were SAb+/GAg+. anti-PLA2R antibody was highly skewed, so natural log transformation was used for the analysis.

Table 4. Multiple linear regression analysis of fibrinogen and clinical indicators in patients with IMN who were SAb+/GAg+.

Fib
	one-way correlation analysis		multiple linear regression analysis
Indicators	r	p	β (95% CI)	p
Anti-PLA2R Antibodies	0.459	<0.001	0.002(0.000, 0.003)	0.015
Alb	−0.457	<0.001	−0.072(−0.119, −0.025)	0.003
SCR	0.219	0.047	―	―
TC	0.227	0.039	―	―
TG	0.293	0.007	―	―
eGFR	−0.228	0.038	―	―
Urinary protein	0.388	<0.001	―	―

IMN: idiopathic membranous nephropathy; SAb: serum anti-phospholipase A2 receptor antibody; GAg: glomerular phospholipase A2 receptor antigen; PLA2R: phospholipase A2 receptor; Fib: fibrinogen; Alb: serum albumin; SCR: serum creatinine; TC: total cholesterol; TG: triacylglycerol; eGFR: estimated glomerular filtration rate.

Table 5. Multiple Linear regression analysis of the MA value and clinical indicators in patients with IMN who were SAb+/GAg+.

MA
	one-way correlation analysis		multiple linear regression analysis
Indicators	r	p	β (95% CI)	p
Anti-PLA2R Antibodies	0.324	0.002	0.006(0.001,0.012)	0.02
Alb	−0.320	0.003	―	―
eGFR	−0.304	0.005	―	―
Urinary protein	0.306	0.004	―	―
PLT	0.479	<0.001	0.032(0.02,0.044)	<0.001
HCT	−0.316	0.003	―	―
Hb	−0.344	0.001	―	―

IMN: idiopathic membranous nephropathy; SAb: serum anti-phospholipase A2 receptor antibody; GAg: glomerular phospholipase A2 receptor antigen; PLA2R: phospholipase A2 receptor; Alb: serum albumin; eGFR: estimated glomerular filtration rate; PLT: platelet count; HCT: hematocrit; Hb: hemoglobin.

Data availability statement

The data underlying this article will be shared upon reasonable request to the corresponding author.