Association of circulating proprotein convertase subtilisin/kexin type 9 concentration with coagulation abnormalities in patients with primary membranous nephropathy

Figures & data

Table 1. General characteristics of the study participants at diagnosis.

Characteristics	Healthy controls	Patients with PMN	p Value
Number	30	87	–
Age (mean ± SD) (years)	45.2 ± 12.8	49.2 ± 13.4	0.153
Sex, Male (%)	15 (50.0%)	48 (55.2%)	0.624
Albumin (mean ± SD) (g/L)	45.9 ± 2.2	27.0 ± 5.5	<0.001
Urinary protein (mean ± SD) (g/24h)	–	5.4 ± 4.4	–
Nephrotic proteinuria, n (%)	–	57 (65.5%)	–
Scr (mean ± SD) (μmol/L)	68.9 ± 12.7	65.5 ± 35.1	0.604
eGFR (mean ± SD) (ml/min/1.73 m^2)	107.7 ± 21.2	118.8 ± 31.5	0.076
PLA2R Abs (median, quartile) (RU/mL)	–	24.42 (2.47,83.98)	–
TC (mean ± SD) (mmol/L)	4.4 ± 0.8	7.2 ± 2.3	<0.001
TG (mean ± SD) (mmol/L)	0.9 ± 0.2	2.3 ± 1.5	<0.001
LDL-C (mean ± SD) (mmol/L)	2.5 ± 0.6	4.6 ± 1.7	<0.001
Leukocytes (mean ± SD) (×10^9/L)	2.0 ± 0.5	6.4 ± 2.3	0.701
Neutrophils (mean ± SD) (×10^9/L)	3.2 ± 0.8	3.7 ± 1.7	0.130
Platelets (mean ± SD) (×10^9/L)	218.0 ± 52.1	257.7 ± 59.4	0.002

PMN: primary membranous nephropathy; SD: standard deviation; Scr: serum creatinine; eGFR: estimated glomerular filtration rate; PLA2R: phospholipase A2 receptor; Abs: antibodies; TC: total cholesterol; TG: Triglycerides; LDL-C: low density lipoprotein cholesterol.

Figure 1. Scatter plot shows the distributions of coaugulation-related parameters. (a) Fibrinogen levels in PMN and health controls. (b–d) Plasma factor VIII, factor IX and factor XI activity in PMN. (e) Tissue factor levels in PMN and health controls. (f–h) Activity of protein C, protein S and AT III in PMN. (i,j) PT and APTT levels in PMN and health controls. PMN, Primary membranous nephropathy; AT III, antithrombin-III; PT, Prothrombin time; APTT, Activated partial thromboplastin time.

Figure 2. Scatter plot shows the levels of PCSK9 in PMN patients and health controls. PCSK9 was highly skewed, so natural log transformation was used for the analysis. PMN, Primary membranous nephropathy; PCSK9, proprotein convertase subtilisin/Kexin type 9.

Figure 3. Association of PCSK9 and coagulation-related indicators in PMN patients. PMN, Primary membranous nephropathy; PCSK9, proprotein convertase subtilisin/Kexin type 9; AT III, antithrombin-III.

Table 2. Independent determinants of clotting factors to log-transformed PCSK9.

Parameters	Factor VIII				Factor IX				Factor XI				Log-transformed TF
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	Beta	p Value	Beta	p Value	Beta	p Value	Beta	p Value	Beta	p Value	Beta	p Value	Beta	p Value	Beta	p Value
Age	0.206	0.057			−0.070	0.521			−0.039	0.725			0.066	0.556
Sex	0.054	0.622			−0.082	0.452			−0.019	0.861			0.013	0.906
Albumin	−0.502	<0.001	−0.439	<0.001	−0.310	0.004			−0.217	0.045			−0.206	0.065
LDL-C	0.308	0.004			0.305	0.004			0.328	0.002			0.167	0.136
Scr	0.387	<0.001	0.284	0.003	0.377	<0.001	0.265	0.004	0.141	0.195			0.261	0.019
Proteinuria	0.419	<0.001			0.416	<0.001	0.254	0.007	0.314	0.003	0.202	0.046	0.198	0.079
Protein C	0.257	0.021			0.412	<0.001	0.212	0.028	0.472	<0.001	0.338	0.001	0.279	0.015
Protein S	0.189	0.090			0.379	<0.001			0.385	<0.001	0.241	0.019	0.266	0.021
AT III	−0.149	0.177			0.042	0.706			0.093	0.400			−0.059	0.608
LnPCSK9	0.267	0.013	0.186	0.047	0.496	<0.001	0.325	0.001	0.217	0.045			0.584	<0.001	0.531	<0.001

LDL-C: low density lipoprotein cholesterol; Scr: serum creatinine; TF: tissue factor; AT-III: antithrombin-III.

Table 3. Independent determinants of PT to log-transformed PCSK9.

	PT
	Beta	p Value
Model 1^a	−0.426	<0.001
Model 2^b	−0.392	0.001
Model 3^c	−0.343	0.011

The multivariable regression stepwise models are shown. The log-transformed PCSK9 is the dependent variable.

^aUnivariable regression analysis of log-transformed PCSK9.

^bAdjusted for age and sex, albumin, LDL- C, Scr and proteinuria.

^cAdjusted for age and sex, albumin, LDL-C, Scr, proteinuria, protein C, protein S, log-transformed TF and AT III.

PT: Prothrombin time; LDL-C: low-density lipoprotein cholesterol; Scr: serum creatinine; TF: tissue factor; AT III: antithrombin-III.

Data availability statement

The datasets used during the current study are available from the corresponding author on reasonable request.