Mercury-Induced Membranous Nephropathy: Clinical and

Pathological Features
Shi-Jun Li, Su-Hua Zhang, Hui-Ping Chen, Cai-Hong Zeng, Chun-Xia Zheng, Lei-Shi Li,
and Zhi-Hong Liu
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, P.R China

Background and objectives: Long-term contact with mercury may induce membranous nephropathy (MN); however, the
clinical pathologic features and pathogenesis of mercury-induced MN have not been investigated.
Design, setting, participants, & measurements: The present study retrospectively evaluated 11 cases of mercury-induced MN
to analyze its causes and its clinical and pathologic features.
Results: A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused
by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and
mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury
concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal
function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly
proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings
showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q.
IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached
complete remission in follow-up after withdrawal from mercury exposure.
Conclusions: Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs
from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible
cause of membranous nephropathy.
Clin J Am Soc Nephrol 5: 439 – 444, 2010. doi: 10.2215/CJN.07571009

M
embranous nephropathy (MN), a disease character-
ized by an accumulation of immune deposits on the
outer aspect of the glomerular basement mem-
brane, is the common cause of idiopathic nephrotic syndrome
in adults (1). MN may be classified as an idiopathic type and a
secondary type associated with other clinical conditions or
diseases, which include infections, autoimmune diseases, toxin
or drugs, cancer, etc. (2).
Mercury-containing compounds have historically been used
in dental amalgams, Chinese traditional medicines, and skin-
lightening creams. Mercury can be absorbed into the human
body by inhalation, ingestion, or intact skin. It has toxicities for
kidneys, nerves, and gastrointestinal tracts. Some literature
reported that exposure to mercury caused acute and chronic
renal lesions (3). Long-term use of mercury-containing skin
lightening cosmetics or occupational contact with mercury
caused MN in sporadic cases (4 – 6). This study evaluated 11
cases of MN diagnosed by renal biopsy that were associated
with chronic mercury exposure, to analyze its clinical and
pathologic features, as well as the relationship between them to
investigate the pathogenesis for better understanding of the
mercury-induced MN.
Materials and Methods
Patient Selection
We retrospectively analyzed 11 cases of MN diagnosed by renal
biopsy in our hospital from June 2004 to June 2008. The selected cases
were required to meet the following criteria: (1) The histologic and
immunopathologic changes of the patient were consistent with those of
MN. (2) The patient had a clear history of contact with mercury-
containing preparations or staying in a mercury-containing environ-
ment. (3) The patient had no history of renal diseases or abnormal
urinary tests before mercury exposure. (4) Systemic lupus erythemato-
sus, hepatitis B, hepatitis C, and tumor associated with MN were
excluded; the patients who had a history of rheumatoid arthritis had no
evidence of prior proteinuria before mercury exposure. No nonsteroi-
dal anti-inflammatory agents, gold preparations, or penicillamine was
ever used. (5) Quantification of urinary mercury concentration was ⬎8
␮g/L, and there was resolution of proteinuria after cessation of expo-
sure to mercury.

Received October 23, 2009. Accepted December 4, 2009.

Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Dr. Zhihong Liu, Professor of Medicine, Research Institute of
Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing
21002, China. Phone: 86-25-80860218; Fax: 86-25-84801992; E-mail: zhihong--
liu@hotmail.com
Data Collection
General Information. Gender, age, duration of contact with mer-
cury-containing preparations, the duration of renal diseases, hyperten-
sion, ultrasound of bilateral kidneys, and extrarenal presentations were
recorded.

Copyright © 2010 by the American Society of Nephrology ISSN: 1555-9041/503–0439

440 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 439 – 444, 2010

Urinalysis. Hematuria under light microscope was defined as a
red blood cell count ⬎10,000/ml in urinary sediment. Proteinuria was
defined as urine protein ⬎0.4 g/24 hours. The urinary N-acetyl-pd
glucosaminidase enzyme (NAG) enzyme was normal when it was less
than 16.5 U/g per creatinine. The urinary retinol-binding protein (RBP)
was normal when it was less than 0.5 mg/dl. The normal urinary
osmolality was higher than 800 mOsm/kg H2O after fasting.
Blood Tests. Hemoglobin, serum creatinine, urea nitrogen, blood
uric acid, albumin, and globulin were recorded. Antinuclear antibody
(ANA), anti-double-stranded DNA antibody, rheumatoid factors (RFs),
anti-ribonuclear protein antibody, anti-SSA antibody, anti-SSB anti-
body, anticardiolipin antibody, complements, and immunoglobulins
were also recorded.
Quantification of Urinary Mercury. The normal concentration
was less 8 ␮g/L by using the cold vapor atomic fluorescence spectrom-
etry.
Pathology. A percutaneous renal biopsy was performed under the
guidance of the ultrasound. Each renal sample contained more than 10
glomeruli. The procedure of renal biopsy was specified as follows: the
samples were embedded in paraffin and sectioned at 2 ␮m, followed by
hematoxylin-eosin, Masson, periodic acid-Schiff, and periodic acid-
silver methenamine (PASM) staining. For immunofluorescence stain-
ing, the samples were sectioned in frozen conditions, followed by
staining for IgG, IgA, IgM, C3, C4, and C1q. The deposits, staining
intensity, and distribution of various immunoglobulins and comple-
ments were observed. The immunofluorescence intensity of immuno-
globulins and complements was graded as negative, 1⫹, or 2⫹. The
electron microscopy observations were done with the Hitachi 7500
electron microscope after routine sections from renal tissues, followed
by double staining with uranyl acetate and lead citrate.
Deposits of IgG Subclass. Indirect immunofluorescence assay
was adopted as previously reported. The slides were prepared in
frozen conditions and dried, sealed with 10% fetal serum, and rinsed
with PBS for 5 minutes. The primary antibodies, including mouse
anti-human IgG1 monoclonal antibody (clone 8c/6-39; Sigma-Aldrich),
mouse anti-human IgG3 monoclonal antibody (clone HP-6050; Sigma-
Aldrich), and mouse anti-human IgG4 monoclonal antibody (clone
HP-6025; Sigma-Aldrich), diluted at 1:400, were added respectively
before culturing for 2 hours. After the slides were rinsed with PBS for
5 minutes, the FITC-labeled rabbit anti-mouse IgG secondary antibody
(1:50; DAKO) was added before culturing for 30 minutes. The slides
were dried and sealed with glycerin for observation under the fluores-
cence microscope. The immunofluorescence intensity of IgG subtypes
was graded as negative, 1⫹, or 2⫹.
Results
General Information
The present research enrolled 10 women and one man rang-
ing in age from 15 to 45 years. The duration of contact with
mercury ranged from 2 to 60 months, and the urinary mercury
concentration ranged from 12 to 400 ␮g/L after hospitalization.
See Table 1.
The causes of 11 cases of mercury-induced MN are listed in
Table 1. Three patients with rheumatoid arthritis (who met
American College of Rheumatology criteria for rheumatoid
arthritis) and one patient with still disease were medicated with
the “antirheumatoid pill” prepared by a hospital; the routine
urine test results were normal before medication. One course of
medication included 120 pills; laboratory analyses indicated
that the pills contained mercury; six pills dissolved in 100 ml of
water amounted to a concentration higher than 0.4 mg/L mer-
cury. Four instances involved use of skin-lightening cream
prepared by a beauty salon; the cream was confirmed to con-
tain 0.8% mercury by weight. One instance involved adminis-
tration of mercury-containing drugs (confirmed by the urinary
mercury concentration) for tuberculosis of breast. One instance
resulted from contact with mercury-containing hair-dyeing
agents (confirmed by the urinary mercury concentration). One
patient worked in a fluorescence light bulb factory and had
contact with mercury vapor for 7 months.
Clinical Presentations
Five patients had red needlepoint-like skin rash with mild
pruritus after administration or contact with mercury-contain-
ing compounds, of whom two patients used skin-lightening

Table 1. General clinical characteristics and etiology in patients of mercury-induced MN

Urinary Duration of
Duration of
Age, Etiology of Mercury Mercury Renal
Case Gender Primary Disease Mercury
yr Poisoning Concentration, Symptoms,
Exposure, mo ␮g/L mo

1 F 24 rheumatoid arthritis antirheumatoid pill 60 ⬎400 12

2 F 45 rheumatoid arthritis antirheumatoid pill 6 200 7
3 F 42 rheumatoid arthritis antirheumatoid pill 5 48 2
4 M 15 still disease antirheumatoid pill 60 22 2
5 F 37 no skin-lightening cream 12 100 6
6 F 39 no skin-lightening cream 8 12 1
7 F 33 no skin-lightening cream 4 120 4
8 F 43 no skin-lightening cream 8 18 3
9 F 38 no mercury-containing 36 27 12
hair dye
10 F 30 tuberculosis of mercury-containing 2 ⬎400 2
breast drugs
11 F 18 no mercury vapor 7 35 3
Clin J Am Soc Nephrol 5: 439 – 444, 2010 Mercury-Induced Membranous Nephropathy 441

cream, two patients were administered the antirheumatoid pill,

g/24 h g/L mg/dl

0.50
0.61
0.52
0.61
0.43
0.58
0.58
0.68
0.58
0.64
0.46
SCr,
and one patient had contact with hair-dyeing agents. A patient

nuclear antibody; NAG, N-acetyl-pd-glucosaminidase enzyme; N, negative; DMPS, sodium dimercaptopropane sulfonate; ACEI, angiotensin-converting enzyme inhibitor;
Last Follow-Up
using skin-lightening cream apparently suffered from a sleep

Hb, hemoglobin; BUN, blood urea nitrogen; SCr, serum creatinine; UA, uric acid; Alb, albumin; Glo, globulin; TC, total cholesterol; TG, total triglyceride; ANA, anti-
disorder. One patient with tuberculosis of the breast had an

45.1
38.5
49.0
43.9
47.1
41.2
41.2
43.5
45.8
48.6
36.9
Protein, Alb,
apparent alanine aminotransferase/aspartate aminotransferase
increase (no history of receiving antituberculosis antibiotics,

mOsm/kg ANA Treatment Follow- Urinary

0.18
0.78
0.11
0.12
0.15
0.13
0.36
0.10
0.10
0.10
1.78
such as rifampin). The other patients had no nervous system
symptoms, such as apparent abnormal feeling, convulsion,
tremor, etc. No patients had dental ulcer, alopecia, or digestive

Up, mo
or respiratory irritation. Apparent anemia occurred in two fe-

48
6
30
18
24
12
14
12
48
36
6
male patients with rheumatoid arthritis; normal peripheral
blood white cell count and platelet count were observed in all
patients. Four patients were ANA-positive. All patients were

DMPS
DMPS

DMPS

DMPS
ACEI
ARB

ARB
ARB

ARB
negative for anti-double-stranded DNA, anti-SSA, anti-SSB,
and anti-ribonuclear protein antibody. Two patients with rheu-
matoid arthritis were rheumatoid factor-positive. Normal C3

1:128

1:512
1:16

1:4
and C4 were noted in all patients.

N
N

N
N

N
N
All patients initially reported edema and proteinuria. No

Urinary Urinary Osmolality,

microscopic or macroscopic hematuria was observed. No pa-
tients had hypertension. The serum creatinine was normal in all

594
541
1002
1158
782
772
739
666
667
604
682
H2O
patients. Nine patients had hypoalbuminemia; three patients
had nephrotic syndrome. The urinary protein spectrum indi-
cated that low-molecular weight proteins existed in nine pa-

mg/L
RBP,

0.38
0.23

0.21
0.17
0.05
0.08
0.09
0.12
2.77
0.13
tients, in two of whom low-molecular weight proteins ac-

0.6
counted for more than 10%. All patients had elevated a urinary
Table 2. Clinical findings at biopsy and follow-up in patients of mercury-induced MN

NAG enzyme content. Increased urinary RBP was observed in

g/24 h creatinine
U/g per

two patients. The urinary osmolality in nine patients was lower

NAG,

40.4
42.2
22.2
35.3
29.3
46.3
37.1
27.5
23.9
85.5
52.3
than the normal range. No urinary glucose or amino acid was
found in any patients (Table 2).
Urinary
mg/dl mg/dl ␮mol/L g/L g/L mmol/L mmol/L Protein,

2.08
1.86

1.49
3.82
3.17
2.39
3.52
1.43

4.76
1.2

3.1
Histologic Findings
Stiff glomerular peripheral capillary loops, slightly thickened
glomerular basement membrane and, occasionally, subepithe-
1.29
0.79
1.83
2.24
1.86
2.77
0.91
0.96
1.01
2.17
2.96
TG,

lial fuchsinophilic deposits on PASM-Masson staining were

observed under light microscopy (Figure 1A). Mild prolifera-
tion of mesangial cells and matrix was observed. No evidence
4.03
5.54
9.78
4.79
7.25
3.86
5.25
5.15
5.47

10.56
TC,

4.4
of fibrinoid necrosis, crescents, or endocapillary proliferation
was observed. Patient nos. 1, 2, 3, and 11 had few glomerular
infiltrating cells, among which neutrophil granulocytes and
24.8
17.2
24.3
27.5
16.2
23.2
17.6
15.1
22.8
22.8
21.7
Alb, Glo,

monocytes counted for the majority. Observed for patient nos 1,

2, and 10 were acute focal tubulointerstitial injuries, partial loss
27.5
31.6
35.5

21.3
29.9

26.1
34.1
27.2
21.1

of the tubular brush border, granular degeneration of epithelial

42

25

cells, and focal concentration of monocyte and neutrophil gran-

ulocyte infiltration (Figure 1B). The other patients had no ap-
UA,

244
180
257
286
347
369
213
406
396
348
271

ARB, angiotensin II receptor blocker.

parent tubulointerstitial injury. Some patients had hyaline de-

generation of afferent arterioles but without infiltration of
inflammatory cells.
0.41
0.70
0.47
0.51
0.56
0.63
0.49
0.85
0.87
0.64
0.51
SCr,

All patients had granular deposits of IgG and C3 along the

capillary loop of glomeruli on immunofluorescence analysis.
Hb, BUN,

6.35

8.52
7.34

8.12
5.23

Additional codeposits of C4 were observed in two patients,

28.2
13.5
10.2
10.5

11.3
14.1

whereas additional codeposits of C4 and C1q were observed in

another six patients. The finding of positivity for all of IgG, IgA,
Case g/dl

9.7
9.0
13.6
14.8
12.8
12.5
12.2
13.1
13.2
12.1
14.1

and IgM, together with C3, C4, and C1q, was present in two
patients (See Table 3). Two patients only had deposits of IgG1,
whereas there were deposits of both IgG1 and IgG4 (predom-
1
2
3
4
5
6
7
8
9
10
11

inantly IgG1) in the others. Two patients showed deposits of

442 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 439 – 444, 2010

tensive effacement of the foot processes of the visceral epithelial

cells.

Treatment and Prognosis

All patients abstained from mercury-containing preparations
after definitive diagnosis. Four patients with a urinary mercury
concentration higher than 100 ␮g/L were treated with sodium
dimercaptopropane sulfonate for mercury detoxification. Five
patients were treated with angiotensin-converting enzyme in-
hibitor/angiotensin II receptor blocker. In follow-up, two pa-
tients were lost in 6 months, for whom the urine protein de-
creased, the serum albumin recovered to a normal range, and
the renal functions remain normal. Nine patients reached com-
plete remission in follow-up 1 to 4 years (see Table 2).

Figure 1. Pathologic findings in mercury-induced MN. (A) Discussion

Thickened glomerular basement membrane, as well as subep-
ithelial fuchsinophilic deposits along the epithelium. Patient
no. 2 (PASM staining; magnification, ⫻400). (B) Loss of the
tubular brush border and focal concentration of interstitial
infiltrating cells. Patient no. 10 (periodic acid-Schiff staining;
magnification, ⫻400). (C) Deposits of IgG1 in the glomerular
basement membrane (2⫹). Patient no. 2 (immunofluorescence
staining; magnification, ⫻400). (D) Deposits of IgG4 in the
glomerular basement membrane (1⫹). Patient no. 2 (immuno-
fluorescence staining; magnification, ⫻400).
IgG1, IgG3, and IgG4 along the capillary loop of glomeruli on
immunofluorescence analysis (Figure 1, C and D; Table 3).
Among 11 patients, two were classified as stage I MN, seven
were stage II MN, one was stage III MN, and one was stage IV
MN according to the electron microscopic finding. Electron
microscopy showed numerous scattered subepithelial deposits
in all patients; some of the deposits were separated from each
other by basement membrane spikes, whereas five patients had
electron-dense deposits in the mesangium. Intramembranous
and subendothelial deposits were not present. There was ex-
Mercury-containing compounds have been used commer-
cially and medically for centuries; it was a common constituent
of Chinese traditional medicines (7). Long-term mercury poi-
soning usually damages several systems, and common symp-
toms include nervous system symptoms, digestive symptoms,
respiratory symptoms, and kidney symptoms (3). In this study,
a few patients had skin rash, elevated liver enzymes, or insom-
nia, and the others did not have apparent nervous system
symptoms, such as abnormal feeling, convulsion, and tremor,
indicating that the majority of the patients’ extrarenal organs or
systems were not obviously implicated. Epidemiologic data
showed that mercury poisoning mainly resulted from occupa-
tional contact with mercury, abuse of mercury-containing com-
pounds, or skin-lightening cosmetics (8,9). In recent years, renal
diseases from mercury poisoning have apparently decreased in
developed countries, but mercury exposure is still not rare in
developing countries, which deserves concern. In this study,
the mercury poisoning instances mainly were related to mer-
cury-containing skin-lightening cream or the mercury-contain-
ing Chinese traditional medicine antirheumatoid pill. The uri-
nary concentrations of mercury in our patients were 1.5 to 50
times higher than reference values for nonexposed populations.

Table 3. Immunofluorescence findings in patients with mercury-induced MN

Case IgG IgA IgM C3 C4 C1q IgG1 IgG3 IgG4

1 1⫹ N N 2⫹ 1⫹ 1⫹ 2⫹ N 1⫹
2 2⫹ 1⫹ 1⫹ 1⫹ 1⫹ 1⫹ 2⫹ N 1⫹
3 2⫹ N N 2⫹ N N 2⫹ 1⫹ 1⫹
4 2⫹ N N 2⫹ 1⫹ N 2⫹ N 1⫹
5 2⫹ 1⫹ 1⫹ 2⫹ 1⫹ 1⫹ 2⫹ N N
6 2⫹ N N 2⫹ N N 1⫹ 1⫹ 1⫹
7 2⫹ N N 1⫹ 1⫹ 1⫹ 2⫹ N 1⫹
8 2⫹ N N 2⫹ 1⫹ N 2⫹ N 1⫹
9 2⫹ N N 1⫹ N N 2⫹ N N
10 2⫹ N N 2⫹ 1⫹ 1⫹ 2⫹ N 1⫹
11 2⫹ N N 1⫹ 1⫹ 1⫹ 2⫹ N 1⫹
N, negative.
Clin J Am Soc Nephrol 5: 439 – 444, 2010
The diagnosis of mercury poisoning rests mainly on a history of
mercury-containing compound exposure; supporting evidence
may be provided by a raised urinary concentration of mercury.
Kidney is the main mercury accumulation and excretion
organ. Acute mercury poisoning mainly results in acute tubular
necrosis, especially with involvement of the proximal tubules
(10), whereas chronic mercury exposure mainly causes immune
complex nephritis, especially MN (11). In this study, all patients
showed membranous nephropathy in pathologic findings;
most of the patients in this study were young and female,
which is not consistent with the epidemiologic finding for
idiopathic MN (2). It is thus hypothesized that they had sec-
ondary MN. In our patients, all patients had long-standing
mercury exposure before proteinuria appeared; none of them
had any other secondary cause of nephropathy, such as sys-
temic lupus erythematosus, malignancies, or viral hepatitis,
and no nonsteroidal anti-inflammatory agent, gold, or penicil-
lamine was ever used. Therefore, membranous nephropathy
was probably related to mercury exposure. It must be indicated
that three patients had a history of rheumatoid arthritis. Be-
cause both rheumatoid arthritis and mercury poisoning may
cause MN, whether their MN results from rheumatoid arthritis
or mercury poisoning is not clear in light of clinical presenta-
tions or pathologic changes. However, considering the fact that
no abnormal urine tests existed before administration of the
mercury-containing traditional medicine antirheumatoid pill,
and that edema, proteinuria, and increased urinary mercury
appear within 6 to 60 months of exposure, one is able to relate
the MN to chronic mercury poisoning rather than rheumatoid
arthritis. In this study, the urinary mercury concentration has
predictive values in diagnosis and treatment for chronic mer-
cury poisoning. The patients were in complete remission after
withdrawal from mercury exposure or the mere therapy of
mercury detoxification without immune suppression, indicat-
ing that chronic mercury poisoning is the ultimate cause of MN.
All patients presented normal kidney function and an in-
creased level of urinary NAG enzyme. The NAG enzyme is a
lysosomal enzyme that is commonly regarded to be predictive
of renal tubular epithelial cell injuries when its level escalates.
In the research, the consistent increase of urinary NAG enzyme
in all patients may be associated with the direct poisoning of
mercury compounds for renal tubular epithelial cells. The uri-
nary NAG enzyme thus tends to be more sensitive than urinary
RBP, and it is thus a preferred factor reflecting the intensity of
injuries of renal tubular epithelial cells in cases of mercury
poisoning (12). Three patients who were recently managed
with mercury-containing traditional medicines demonstrated
acute focal injuries of renal tubules. The other patients had no
apparent tubular interstitial lesions, which is consistent with
the finding in a previous study that the interstitial lesions were
mild in patients using skin-lightening cosmetics (4).
The immunofluorescence findings showed that eight patients
had codeposits of C4 and/or C1q associated with Ig in glomer-
ular deposits. In two patients, a “full house” pattern, which is
often observed in lupus nephritis (none of our patients showed
any feature of systemic lupus erythematosus at the time of
biopsy or follow-up), indicating activation of the classical com-
Mercury-Induced Membranous Nephropathy 443
plement pathway, as opposed to only deposits of IgG and C3 in
idiopathic MN. It is considered that the pathogenesis of mer-
cury-induced MN differs from that of idiopathic MN. To fur-
ther investigate the pathogenesis of mercury-induced MN, the
glomerular IgG subclass was observed. The deposits of both
IgG1 and IgG4 (predominantly IgG1) were observed for mer-
cury-induced MN, which differed from the feature of deposits
of IgG4 in idiopathic MN (13) but was similar to the secondary
MN due to malignancy (14). The distribution of IgG subclass
varies because of the Th1 and Th2 predominant immune re-
sponses: IgG1 and IgG3 are involved in the Th1-type predom-
inant immune response, whereas IgG4 is more active in the
Th2-type predominant immune response (15). In idiopathic
MN, the Th2-type response predominates and moderates the
humoral immune response, whereas the deposits of glomerular
both IgG1 and IgG4 in mercury-induced MN indicate that both
Th1 and Th2 participate in the immune response. The research
on the animal model also demonstrated that Th1 and Th2 were
both involved in mercury-induced autoimmunity (16). The dis-
tribution of glomerular IgG subclass further confirms the diag-
nosis of mercury-induced MN rather than idiopathic MN for
patients in the research.
The mechanism of mercury-induced MN is still uncertain. In
highly susceptible mice, the mercury-induced autoimmune dis-
ease is characterized by a T cell-dependent polyclonal B cell
activation, by mainly increased serum levels of IgG and IgE
antibodies, by the production of ANA, and by the formation of
renal immune complex deposits, and thus induced MN in
susceptible mice and rats (17–20). In this study, four female
patients were ANA-positive, of whom two were rheumatoid
arthritis patients, whereas the other two suffered no autoim-
mune diseases before mercury exposure, implying that mer-
cury exposure might induce autoimmune antibodies. Theoret-
ically, a small fraction of humans may be susceptible to the
development of autoimmunity; T cell-dependent polyclonal B
cell activation might result in the production of antibodies
against membrane proteins of podocyte similar to those in
idiopathic MN. Such antibodies render specificity to M-type
phospholipase A2 receptor, an antigen normally expressed on
the podocyte cell membrane in humans (21). Whether the mer-
cury-induced renal immune complex deposits are formed by
accumulation of circulating immune complexes in the kidney
or by direct binding of autoantibodies to the self-components of
podocytes, then in situ immune complex formation remains to
be elucidated.
Conclusions
The clinical and pathologic features of mercury-induced MN
are not significantly different from those of idiopathic MN.
Because mercury-containing compounds are still widely avail-
able in developing countries, it is important that clinicians are
aware that mercury exposure should be considered a possible
cause of membranous nephropathy, because it is likely to be
missed unless specifically enquired for. In clinical practice, it is
thus necessary to observe deposits of complements and IgG
subclasses, inquire specifically about the history of use of mer-
cury-containing skin lightening cosmetics or traditional medi-
444 Clinical Journal of the American Society of Nephrology
cines, and conduct urine tests in appropriate patients to exclude
renal injuries due to mercury exposure. Once a definitive diag-
nosis is reached, patients should abstain from the mercury
exposure, and immune suppression should be carefully
avoided.
Disclosures
None.
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