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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2019, Vol. 13 Issue (5) : 618-625    https://doi.org/10.1007/s11684-018-0620-5
RESEARCH ARTICLE
Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model
Hanyu Zhu1, Bo Fu1, Yong Wang1(), Jing Gao2, Qiuxia Han3, Wenjia Geng1, Xiaoli Yang1, Guangyan Cai1, Xiangmei Chen1, Dong Zhang1()
1. Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing 100853, China
2. Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China
3. Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Abstract

This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.
Keywords multiparameter analysis      diagnosis      model      membranous nephropathy     
Corresponding Author(s): Yong Wang,Dong Zhang   
Just Accepted Date: 24 April 2018   Online First Date: 09 August 2018    Issue Date: 14 October 2019
 Cite this article:   
Hanyu Zhu,Bo Fu,Yong Wang, et al. Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model[J]. Front. Med., 2019, 13(5): 618-625.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0620-5
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I5/618
Index full name Abbreviation Reference range
Anti-phospholipase A2 receptor antibodies Anti-PLA2R antibodies 0−20 RU/mL
Alanine aminotransferase ALT 0−40 U/L
Aspartate aminotransferase AST 0−40 U/L
Total protein TP 55−80 g/L
Albumin ALB 35−50 g/L
Total bilirubin TB 0−21 mmol/L
Direct bilirubin DB 0−8.6 mmol/L
Alkaline phosphatase ALP 0−130 U/L
g-Glutamyltransferase GGT 0−50 U/L
Glucose GLU 3.4−6.2 mmol/L
Urea nitrogen UN 1.8−7.5 mmol/L
Creatinine Cr 30−110 mmol/L
Uric acid Ua 104−444 mmol/L
Total cholesterol CH 3.1−5.7 mmol/L
Triglyceride TG 0.4−1.7 mmol/L
Creatine kinase CK 2−200 U/L
Lactate dehydrogenase LDH 40−250 U/L
High-density lipoprotein cholesterol HDL 1−1.6 mmol/L
Low-density lipoprotein cholesterol LDL 0−3.4 mmol/L
Thrombin time TT 16.0−18.0 s
Prothrombin time PT 11.0−15.0 s
Plasma fibrinogen FIB 200−400 mg/dL
D-dimer D2 0.0−0.5 mg/L
Immunoglobulin A IgA 70−180 mg/dL
Immunoglobulin G IgG 700−1600 mg/dL
Immunoglobulin M IgM 40−230 mg/dL
Immunoglobulin E IgE 0−100 IU/mL
Complement 3 C3 90−180 mg/dL
Complement 4 C4 10−40 mg/dL
Body mass index BMI 18.5−24.99
Activated partial thromboplastin time APTT 30−45 s
Prothrombin activity PTA 70%−150%
Tab.1  Biological parameters assessed in the present study
Clinicopathologic features Number of cases (n, %) MN group (n, %) Non-MN group (n, %) c2 P value
Total 798 (100) 248 (31.08) 550 (68.92)
Age (year) 49.115 0.000
<45 464 (58.15) 99 (39.91) 365 (66.36)
≥45 334 (41.85) 149 (60.09) 185 (33.64)
Hypertension 13.537 0.000
Yes 370 (46.37) 91 (36.69) 279 (50.73)
No 428 (53.63) 157 (63.31) 271 (49.27)
Gender 1.714 0.190
Male 487 (61.03) 143 (57.66) 344 (65.55)
Female 311 (38.97) 105 (42.34) 206 (37.45)
Diabetes 1.562 0.211
Yes 115 (14.41) 30 (12.10) 85 (15.45)
No 683 (85.59) 218 (87.90) 465 (84.55)
NS 154.875 0.000
Yes 311 (38.97) 176 (70.97) 135 (24.55)
No 487 (61.03) 72 (29.03) 415 (75.45)
IgAN 164.466 0.000
Yes 280 (35.09) 7 (2.82) 273 (49.64)
No 518 (64.91) 241 (97.18) 277 (50.36)
Tab.2  Differences in clinicopathological features between MN and non-MN groups
Parameter Mean±SD
MN group non-MN group
BMI 25.89±4.69 25.22±4.23
Anti-PLA2R antibodies 97.56±183.78** 2.73±8.75
ALT (U/L) 21.05±16.64 23.69±25.27
AST (U/L) 18.53±9.06 19.13±12.13
TP (g/L) 49.36±9.94* 61.07±11.70
ALB (g/L) 26.98±6.99* 36.10±8.90
TB (mmol/L) 7.77±3.57* 8.96±4.63
DB (mmol/L) 1.49±1.15* 2.16±1.33
ALP (U/L) 58.95±16.55* 69.50±36.20
GGT (U/L) 35.42±48.55 33.97±55.55
GLU (mmol/L) 4.91±1.21 4.98±1.90
UN (mmol/L) 5.21±2.41** 6.83±3.97
Cr (mmol/L) 75.86±25.93** 115.20±75.14
Ua (mmol/L) 345.78±95.38 374.43±104.02
CH (mmol/L) 7.08±2.33 5.38±2.23
TG (mmol/L) 2.54±1.86 2.09±1.38
CK (U/L) 101.31±135.22 93.31±76.94
LDH (U/L) 194.79±58.53 179.47±59.33
HDL (mmol/L) 1.45±0.52 1.22±0.95
LDL (mmol/L) 4.86±2.02* 3.55±1.86
TT (s) 17.24±1.62 16.43±1.52
APTT 36.27±5.99 37.45±4.61
PT (s) 12.96±2.10 13.21±1.16
PTA 107.92±15.88 100.74±13.56
Serum fibrinogen 4.88±1.49 4.03±1.49
D2 (mg/L) 1.28±2.32* 0.86±1.48
IgA (mg/dL) 215.11±84.46* 276.09±123.41
IgG (mg/dL) 622.33±280.82** 935.78±380.02
IgM (mg/dL) 115.39±77.72 112.30±139.87
IgE (IU/mL) 124.77±187.59** 262.64±1071.52
C3 (mg/dL) 113.95±24.64 105.47±26.91
C4 (mg/dL) 27.99±9.68 25.91±9.40
Tab.3  Differences in biological parameters between MN and non-MN groups
Fig.1  Diagnostic values of anti-PLA2R antibodies, UN, Cr, IgG, and IgE were analyzed in 798 patients through ROC analysis. (A) The diagnostic value of anti-PLA2R antibodies; (B) the diagnostic values of UN, Cr, IgG, and IgE. The AUCs of anti-PLA2R antibodies, UN, Cr, IgG, and IgE were 0.854, 0.640, 0.730, 0.755, and 0.481, respectively.
B S.E. Wald df Sig. Exp (B) 95% CI for EXP(B)
Lower Upper
Anti-PLA2R antibodies 0.080 0.014 32.146 1 0.000 1.083 1.054 1.113
Cr -0.030 0.005 38.813 1 0.000 0.971 0.962 0.980
IgG -0.002 0.000 30.439 1 0.000 0.998 0.998 0.999
Constant 2.290 0.477 23.043 1 0.000 9.872
Tab.4  Parameters used in multivariate logistic regression analysis for diagnostic model establishment
Fig.2  Diagnostic value of the “anti-PLA2R antibodies+ IgG+ Cr” combination in MN was examined through ROC analysis. The ROC curve revealed that the “anti-PLA2R antibodies+ IgG+ Cr” combination could be used to distinguish between patients with MN and patients without MN, with an AUC value of 0.917, a cutoff value of 0.34, a sensitivity of 79.9%, and a specificity of 89.4%.
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