Cholinesterase is a Potential Biomarker with High Accuracy for the Nephrotic Syndrome Diagnosis in Minors

Figures & data

Table 1 Demographic Data and Laboratory Parameters of NS, Nephritis and Healthy Minors

Parameters	NS			Nephritis	Healthy
	Total	First Episode	Relapsers
N	138	101	37	104	109
Age (Year)	8.6 ± 6.0	7.4 ± 5.9*^▲	11.9 ± 5.4**^▲▲	9.6 ± 3.9	8.8 ± 3.8
CHE (KU/L)	14.0 ± 3.5**^▲▲	14.7 ± 3.4**^▲▲	12.2 ± 3.1**^▲▲	8 ± 2.0	9.4 ± 1.7
ALT (U/L)	14 (10, 21)*	13 (10, 20)	17 (11, 23)*^▲	12 (8, 9)	12 (10, 17)
AST (U/L)	30 (22, 39)**^▲▲	31 (26, 41)**^▲▲	24 (20, 33)	23 (19, 31)	25 (21, 29)
ALP (U/L)	217 (126, 282)^▲▲	238 (150, 290)^▲▲	155 (81, 244)*^▲▲	209 (139, 267)	273 (239, 339)
GGT (U/L)	12 (9, 21)	11 (9, 18)	18 (12, 33)**^▲▲	12 (9, 15)	12 (10, 15)
GLU (mmol/L)	5.2 ± 1.2	5.2 ± 1.1	5.3 ± 1.5	5.5 ± 0.9	5.0 ± 0.5
TP (g/L)	40 (37, 44)**^▲▲	40 (37, 43)**^▲▲	43 (36, 54)**^▲▲	67 (61, 72)	71 (68, 74)
ALB (g/L)	16 (14, 19)**^▲▲	16 (14, 18)**^▲▲	17 (14, 33)**^▲▲	40 (35, 44)	47 (45, 49)
PA (mg/dL)	13 (10, 18)**^▲▲	12 (9, 15)**^▲▲	16 (12, 21)*^▲▲	19 (14, 23)	23 (21, 26)
Scr (μmol/L)	41 (27, 70)**	40 (26, 58)**^▲	56 (35, 78)^▲	65 (43, 75)	43 (34, 58)
BUN (mmol/L)	4.5 (3.5, 6.5)	4.3 (3.4, 5.9)	4.9 (3.8, 7.6)^▲▲	4.7 (3.9, 6.4)	4.3 (3.6, 5.0)
UA (μmol/L)	330 (271, 426)^▲▲	324 (267, 403)^▲▲	385 (273, 491)*^▲▲	313 (240, 398)	267 (232, 336)
TC (mmol/L)	10.6 (8.2, 12.5)**^▲▲	10.7 (8.6, 12.1)**^▲▲	9.2 (5.4, 13.8)**^▲▲	3.9 (3.4, 4.4)	4.0 (3.5, 4.5)
TG (mmol/L)	2.6 (1.9, 4.1)**^▲▲	2.5 (1.9, 4.1)**^▲▲	3.1 (1.8, 4.2)**^▲▲	1.0 (0.8, 1.5)	0.9 (0.7, 1.3)
TB (μmol/L)	3.6 (2.4, 5.2)**^▲▲	3.1 (2.3, 4.4)**^▲▲	5.2 (3.8, 6.8)**^▲▲	6.6 (4.6, 9.0)	8.4 (6.3, 12.2)
DB (μmol/L)	0.7 (0.4, 1.2)**^▲▲	0.6 (0.4, 1.0)**^▲▲	1.1 (0.7, 1.6)**^▲▲	2.4 (1.6, 3.2)	3.0 (2.1, 4.3)

Notes: *Means a P value < 0.05, **P < 0.01 when Total / First episode / Relapsers vs Nephritis; ^▲Means a P value < 0.05, ^▲▲P < 0.01 when Total / First episode / Relapsers vs Healthy.

Abbreviations: CHE, Cholinesterase; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALP, Alkaline phosphatase; GGT, γ-glutamyl transpeptidase; GLU, Glucose; TP, Total protein; ALB, Albumin; PA, Prealbumin; Scr, Serum creatinine; BUN, Blood urea nitrogen; UA, Uric acid; TC, Total cholesterol; TG, Triglyceride; TB, Total bilirubin; DB, Direct bilirubin.

Table 2 Association of Laboratory Parameters with the Risk of NS (Univariable Logistic Regression Analysis)

Parameters	Total		First Episode		Relapsers
	OR	95% CI	OR	95% CI	OR	95% CI
Age (Year)	0.98	0.93–1.02	0.92	0.87–0.97**	1.17	1.07 −1.28**
CHE (KU/L)	2.43	2.02–2.92**	2.89	2.62–3.69**	1.83	1.45–2.24**
ALT (U/L)	1.01	1.00–1.03	1.01	1.00–1.03	1.01	1.00–1.04
AST (U/L)	1.02	1.01–1.04**	1.03	1.01–1.05**	1.00	0.97–1.02
ALP (U/L)	1.00	0.99–1.00	1.00	0.99–1.00	0.99	0.99–1.00
GGT (U/L)	1.01	1.00–1.02	1.01	0.99–1.02	1.03	1.01–1.04**
GLU (mmol/L)	0.97	0.78–1.22	0.94	0.72–1.24	1.03	0.71–1.51
TP (g/L)	0.78	0.75–0.82**	0.72	0.67–0.79**	0.83	0.79–0.87**
ALB (g/L)	0.77	0.73–0.81**	0.66	0.58–0.75**	0.82	0.78–0.87**
PA (mg/dL)	0.83	0.79–0.87**	0.81	0.76–0.85**	0.88	0.83–0.93**
Scr (μmol/L)	0.99	0.98–1.00	0.98	0.96–0.99**	1.01	0.99–1.02
BUN (mmol/L)	1.03	0.96–1.12	0.99	0.96–0.99**	1.10	0.99–1.02
UA (μmol/L)	1.00	1.00–1.01	1.00	1.00–1.01	1.01	1.00–1.01
TC (mmol/L)	3.22	2.46–4.22**	4.22	2.91–6.11**	2.21	1.69–2.89**
TG (mmol/L)	4.08	2.97–5.61**	4.24	3.00–6.12**	2.96	2.08–4.22**
TB (μmol/L)	0.63	0.57–0.71**	0.52	0.44–0.61**	0.80	0.70–0.90**
DB (μmol/L)	0.17	0.11–0.25**	0.10	0.06–0.18**	0.27	0.17–0.44**

Notes: **Means a P value<0.01. Nephritis and healthy minors as control group.

Abbreviations: CHE, Cholinesterase; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALP, Alkaline phosphatase; GGT, γ-glutamyl transpeptidase; GLU, Glucose; TP, Total protein; ALB, Albumin; PA, Prealbumin; Scr, Serum creatinine; BUN, Blood urea nitrogen; UA, Uric acid; TC, Total cholesterol; TG, Triglyceride; TB, Total bilirubin; DB, Direct bilirubin.

Table 3 The Risk Factors for NS by Logistic Regression Analysis (Multivariate Logistic Regression Analysis)

Parameters	Total		First Episode		Relapsers
	OR	95% CI	OR	95% CI	OR	95% CI
CHE (KU/L)	2.23	1.57–3.18**	4.02	1.47–11.08**	2.04	1.42–2.93**
TP (g/L)	0.83	0.77–0.89**	0.75	0.63–0.90**	0.84	0.78–0.91**
PA (mg/dL)	–	–	–	–	0.86	0.76–0.98*
DB (μmol/L)	0.44	0.22–0.88**	–	–	–	–

Notes: *Means a P value<0.05, **P<0.01. Nephritis and healthy minors as control group.

Abbreviations: CHE, Cholinesterase; TP, Total protein; PA, Prealbumin; DB, Direct bilirubin.

Table 4 Correlations Between CHE and Laboratory Parameters in Total/First Episode/Relapsing NS

Parameters	Total		First Episode		Relapsers
	r value	P value	r value	P value	r value	P value
Age (Year)	−0.185	0.030	−0.111	0.270	−0.006	0.973
ALT (U/L)	−0.238	0.005	−0.258	0.009	−0.267	0.111
AST (U/L)	−0.026	0.758	−0.132	0.187	−0.033	0.847
ALP (U/L)	0.138	0.107	0.034	0.739	0.102	0.549
GGT (U/L)	−0.050	0.567	0.070	0.496	0.068	0.704
GLU (mmol/L)	0.082	0.349	0.144	0.165	0.003	0.986
TP (g/L)	−0.171	0.048	0.078	0.450	−0.297	0.074
ALB (g/L)	−0.359	<0.001	−0.286	0.004	−0.345	0.037
PA (mg/dL)	−0.320	<0.001	−0.312	0.002	−0.157	0.352
Scr (μmol/L)	−0.119	<0.001	−0.094	0.353	0.105	0.535
BUN (mmol/L)	0.076	0.376	0.086	0.392	0.309	0.063
UA (μmol/L)	0.119	0.172	0.157	0.127	0.319	0.054
TC (mmol/L)	0.429	<0.001	0.510	<0.001	0.385	0.019
TG (mmol/L)	0.151	0.084	0.165	0.109	0.218	0.196
TB (μmol/L)	−0.162	0.061	0.000	0.998	−0.114	0.502
DB (μmol/L)	−0.153	0.076	−0.020	0.845	−0.238	0.157

Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALP, Alkaline phosphatase; GGT, γ-glutamyl transpeptidase; GLU, Glucose; TP, Total protein; ALB, Albumin; PA, Prealbumin; Scr, Serum creatinine; BUN, Blood urea nitrogen; UA, Uric acid; TC, Total cholesterol; TG, Triglyceride; TB, Total bilirubin; DB, Direct bilirubin.

Table 5 The Diagnostic Value of CHE for Total/First Episode/Relapsing NS

NS	Cut-Off Value (KU/L)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	AUC	95% CI for AUC	Youden Index (%)
Total	11	87.0	88.7	83.3	91.3	0.93	0.91, 0.96	75.7
First episode	11	94.1	88.7	79.8	96.9	0.96	0.94, 0.98	82.8
Relapsers	11	67.6	88.7	51.0	94.0	0.85	0.78, 0.92	56.3

Abbreviations: PPV, Positive predictive value; NPV, Negative predictive value; AUC, Area under the curve; CI, confidence interval.

Figure 1 ROC curve demonstrating sensitivity and specificity of the CHE to detect total NS.

Figure 2 ROC curve demonstrating sensitivity and specificity of the CHE to detect the first episode of NS.

Figure 3 ROC curve demonstrating sensitivity and specificity of the CHE to detect relapsing NS.