Prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy: a retrospective study of 420 biopsy-proven cases

Figures & data

Figure 1. The study flowchart. GN: glomerulonephritis; HBV, hepatitis B virus; MN: membranous nephropathy.

Figure 2. Detection of viral antigens and particles in renal tissues. Immunohistochemical staining of frozen renal tissue sections. (A) HBsAg and (B) HBcAg antigens are located in the glomeruli as indicated by brown staining in the glomeruli.

Table 1. Distribution of serum HBV markers among patients with pathologically proven glomerulonephritis (N = 420).

HBV markers
Seropositive, n(%)	230(54.8)
HBsAg, HBeAg, HBcAb (+)	16(3.8)
HBsAg, HBeAb, HBcAb (+)	13(3.1)
HBsAb, HBeAb, HBcAb (+)	38(9.1)
HBsAb (+)	73(17.4)
HBeAb, HBcAb (+)	47(11.2)
Others	43(10.2)
Seronegative, n(%)
HBsAg, HBeAg, HBsAb, HBeAb, HBcAb (−)	190(45.2)

Notes: HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBsAb: hepatitis B surface antibody; HBcAg: hepatitis B core antigen; HBcAb: hepatitis B core antibody; HBeAg: hepatitis B e antigen; HBeAb: hepatitis B e antibody.

Table 2. Demographic And baseline characteristics of the study subjects.

Variables	All	Seropositive HBV-MN	Seronegative HBV-MN	p
N	420	230	190	.35
Age, years
Mean (SD)	45.1(15.6)	46.4(16.1)	43.6(14.8)	.56
Range	14,82	14,79	14,82
Gender
Male	234(55.7%)	137(59.6%)	96(50.5%)	.64
Course of disease, months
Mean (SD)	7.76(15.17)	7.40(15.27)	7.45(14.32)	.95
Range	0.1, 144	0.2,144	0.1,120
24-h urinary protein excretion, g/day
Mean (SD)	4.73(2.59)	4.84(2.61)	4.61(2.44)	.34
Range	0.37,14.38	0.37,14.38	0.63,12.57
Serum creatinine(μmol/L)
Mean (SD)	67.1(26.1)	70.42(26.73)	63.63(21.68)	.008
Range	30,307	30,307	33,220
Hypertension, n(%)	144(34.3)	77(33.5)	67(35.3)	.70
Hematuria, n(%)	338(80.5)	182(79.1)	156(82.1)	.44
History of hepatitis B, n(%)	17(4.0)	17(7.4)	0
ALT > 40 U/L, n(%)	20(4.8)	16(7.0)	4(2.1)	.02
eGFR, mL/min/1.73 m^2
CKD1	355(84.5%)	188(81.7%)	167(87.9%)	.47
CKD2	45(10.7%)	28(12.2%)	17(8.9%)
CKD3a	13(3.1%)	9(3.91%)	4(2.1%)
CKD3b	3(0.7%)	2(0.9%)	1(0.5%)
CKD4	4(1.0%)	3(1.3%)	1(0.5%)
CKD5	0	0	0
Clinical manifestation^a
Nephrotic syndrome	286(68.1%)	159(69.1%)	127(66.8%)	.92
Chronic glomerulonephritis	129(30.7%)	68(29.6%)	61(32.1%)
Latent glomerulonephritis	4(1.0%)	2(0.9%)	2(1.1%)
Rapidly progressive glomerulonephritis	1(0.2%)	1(0.4%)	0

Notes: ALT: alanine aminotransferase; CKD: chronic kidney disease; eGFR: estimated glomerular filtration; MN: membranous nephropathy; HBV: hepatitis B virus.

^aNephrotic syndrome is a group of symptoms including protein in the urine (more than 3.5 g/24h), Low serum albumin levels(less than 30 g/L), high cholesterol levels, high triglyceride levels, and swelling. Chronic glomerulonephritis refers to proteinuria, hematuria, hypertension, edema as the basic clinical manifestations, the condition is prolonged, the lesion slowly progresses, can varying degrees of renal function decline; Latent glomerulonephritis, also known as asymptomatic proteinuria or hematuria, has abnormal urine routine examination findings, but no edema, hypertension or renal dysfunction such as performance. Rapidly progressive glomerulonephritis (RPGN) is a clinical and pathological syndrome; a term used to describe the following Rapid loss of renal function over a very short period (days to weeks). Nephritic urine analysis: proteinuria, micro or macroscopic hematuria, dysmorphic red blood cells (RBC), RBC casts. Histopathological characteristic on renal biopsy finding; cellular crescent formation in the glomeruli.

Table 3. Pathological characteristics of the study population.

	All	Seropositive HBV-MN	Seronegative HBV-MN	p
Membranous nephropathy, n(%)	420(100)	230	190
Simple	392(93.3)	215(93.5)	177(93.2)	.90
Complicated	28(6.7)	15(6.5)	13(6.8)
ischemic nephropathy	13(3.1)	8(3.5)	5(2.6)
tubulointerstitial lesion	9(2.1)	6(2.6)	3(1.6)
IgA nephropathy	3(0.7)	1(0.4)	2(1.1)
obesity-related glomerulopathy	2(0.5)	0	2(1.1)
diabetic nephropathy	1(0.2)	0	1(0.5)
Immune fluorescence distribution of IgG subtypes, n(%)	348(100)	197	151
IgG1(+)	1(0.3)	1	0	.97
IgG2 or IgG3(+)	0(0)	0	0
IgG4(+)	7(2.0)	5	2
IgG1, IgG4(+)	34(9.8)	20	14
IgG1, IgG2, IgG4(+)	173(49.7)	99	74
IgG1, IgG3, IgG4(+)	37(10.6)	19	18
IgG1, IgG2, IgG3, IgG4(+)	89(25.6)	49	40
Others	7(2.0)	4	3

Notes: MN, membranous nephropathy; HBV, hepatitis B virus.

Table 4. Comparative analysis of the clinicopathological data between the anti-PLA2R antibody-positive and negative groups.

Parameters	anti-PLA2R antibody-negative(n = 155)	anti-PLA2R antibody-positive(n = 125)	p
Age(years)	47.6 ± 14.9	48.4 ± 13.7	.616
Gender(male/%)	95(61.3%)	72(57.6%)	.532
Hematuria, n (%)	36(23.2%)	25(20.0%)	.516
Hypertension, n (%)	72(46.5%)	52(41.6%)	.417
Serum albumin (g/L)	30.2 ± 6.5	26.1 ± 4.3	<.001
Serum creatinine(μmol/L)	80.2 ± 29.1	78.3 ± 30.7	.752
eGFR (ml/min/1.73m^2)	96.8 ± 25.0	94.8 ± 23.9	.503
Proteinuria (g/24h)	5.7 ± 3.6	6.7 ± 3.3	.018
Uric acid(umol/L)	385.9 ± 96.2	375.6 ± 98.6	.419
Triglycerides (mmol/L)	2.6 ± 1.6	2.8 ± 2.0	.329
Cholesterol (mmol/L)	6.8 ± 2.0	8.1 ± 2.5	<.001
Serum-IgG (mg/dl)	751.9 ± 321.7	614.9 ± 230.1	<.001
Serum-IgM (mg/dl)	109.8 ± 54.2	111.4 ± 52.5	.791
Serum-IgA (mg/dl)	225.7 ± 104.6	225.8 ± 110.8	.995
Serum-C3 (mg/dl)	102.1 ± 22.9	99.8 ± 22.1	.387
Serum-C4 (mg/dl)	24.6 ± 7.2	25.5 ± 7.0	.270
IgG deposit, n (%)	152(98.1%)	124(99.2%)	.772
IgM deposit, n (%)	115(74.2%)	98(78.4%)	.412
IgA deposit, n (%)	141(91.1%)	115(92.0%)	.759
C3 deposit, n (%)	148(95.5%)	122(97.6%)	.343
C1q deposit, n (%)	142(91.6%)	114(91.2%)	.902
IgG1 deposit, n (%)	153(98.7%)	122(97.6%)	.487
IgG2 deposit, n (%)	132(85.2%)	97(77.6%)	.103
IgG3 deposit, n (%)	29(18.7%)	21(16.8%)	.678
IgG4 deposit, n (%)	142(91.6%)	123(98.4%)	.012

Note: The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula [16].

Stevens LA, Claybon MA, Schmid CH, et al. Evaluation of the chronic kidney disease epidemiology collaboration equation for estimating the glomerular filtration rate in multiple ethnicities. Kidney Int. 2011;79(5):555–562. doi: 10.1038/ki.2010.462.

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