letters to the editor

372 N efrologia 2011;31(3):358-78

Membranous
glomerulonephritis
in a patient with syphilis
N efrologia 2011;31(3):372-3
doi:10.3265/N efrologia.pre2011.M ar.10819
To the Editor,
La glomerulonefritis membranosa Mem-
branous glomerulonephritis (MGN)
1
is
the second most prevalent renal patho-
logy to be identified in biopsies. One of
the most common causes of nephrotic
syndrome in the adult population, it is
characterised by the formation of immu-
ne complexes, predominantly IgG and
complement, on the subepithelial side of
the glomerular capillaries, and this is as-
sociated with increased proteinuria.
2
In general, its aetiology is idiopathic or
primary and, less frequently, secondary
(immunological, infectious, drug and
medication-related, or neoplastic).
Unfortunately, it is difficult to distinguish
primary from secondary forms by histo-
logical means,
2
so explicit clinical infor-
mation, including the age of the patient,
history of exposure to medicines or toxic
substances, serological tests and suspect-
ed neoplasias which are linked to the
pathology, is required.
The importance of serological tests lies in
their ability to confirm the diagnosis. In the
case of syphilis screening, non-treponemal
tests are performed: the VDRL (Venereal
Disease Research Laboratory) and RPR (rap-
id plasma reagin) tests. If the results are pos-
itive, the more specific treponemal tests are
performed to confirm the diagnosis: FTA-
ABS (absorption of fluorescent antibodies by
Treponema) and MHA-TP(Treponema pal-
lidum microhaemagglutination). They must
be repeated three and six months later to en-
sure the response to treatment.
The case which concerns us is relevant,
owing to the small number of publica-
tions on the association between
syphilis and MGN.
The patient was a 27-year-old, white,
Caucasian male with a history of cryp-
sis was confirmed by transbronchial
biopsy. The analytical profile was indica-
tive of sarcoidosis (hypercalcaemia, hy-
percalciuria, high levels of vitamin D and
ACE and substantial iPTH suppression).
Renal function impairment in sarcoidosis
is generally due to hypercalcaemia, hyper-
calciuria and nephrocalcinosis, although
nephrolithiasis, glomerulopathies and in-
terstitial nephritis (with or without sarcoid
granuloma) form part of the spectrum of
renal pathologies in sarcoidosis.
1
Corticosteroids
5
are the treatment of
choice and in the case presented here a
good response was obtained. Renal in-
volvement without the lungs being af-
fected is very rare
2
and in this case it was
not possible to establish that this was the
case until the lung biopsy was per-
formed. When we are faced with a case
of renal failure associated with hypercal-
caemia, sarcoidosis should be suspected,
even though there is no clinical manifes-
tation of lung pathology.
1. G obel U , Kettritz R, Schneider W , Luft F.
The protean face of renal sarcoidosis. J A m
Soc Nephrol 2001;12(3):616-23.
2. Baughm an RP, Teirstein A S, Judson M A ,
Rossm an M D, Yeager H Jr, Bresnitz EA, et al.
C linical characteristics of patients in a case
control study of sarcoidosis. Am J Respir Crit
Care M ed 2001;164(10 Pt 1):1885-9.
3. Sharm a O P. Vitam in D , calcium , and
sarcoidosis. Chest 1996;109(2)535-9.
4. Rom er FK. A ngiotensin-converting enzym e
in sarcoidosis. A cta M ed Scand 1979;206(1-
2):27-30.
5. N unes H BD , Valeyre D . Sarcoidosis
treatm ent. Rev Prat 2008;58(10):1099-104.
O. Ibrik
1
, R. Samon
1
, A. Roda
1
, R. Roca
1
,
J.C. Gonzlez
1
, J. Viladoms
1
, J. Vilaseca
2
,
M. Serrano
2
1
Servicio de N efrologa. H ospital de M ollet.
M ollet del Valls. Barcelona.
2
Servicio de N eum ologa. H ospital de M ollet.
M ollet del Valls. Barcelona.
Correspondence: O. Ibrik
Servicio de N efrologa. H ospital de M ollet.
Pau C asals, 20, 3.-1..
08150 M ollet del Valls. Barcelona.
22721aii@ com b.cat
oibrik@ yahoo.es
torchidism, adenoidectomy and amyg-
dalectomy in childhood. He was an ac-
tive smoker, a social drinker and a ho-
mosexual. Two months before being
assessed by our department and, coin-
ciding with a slight pharyngodynia, an
induration had appeared in the patients
right groin, as well as ulcerated serpigi-
nous lesions on the penis and a whitish
urethral discharge, which was initially
treated with azithromycin. While wait-
ing for the serological results, maculo-
papular lesions were observed in the
surrounding area on the thighs and
trunk. They spread to the patients feet
and hands, progressing through differ-
ent phases with no signs of fever, and
accompanied by oedema of the lower
limbs and genitals, with a slight increase
in the abdominal perimeter and a de-
crease in diuresis, which is why the case
was reported to us. The patients urine
was normal in colour, with no evidence
of dysuria or blood in the urine. Blood
pressure (BP) was within normal limits.
The analytical findings of note were
as follows: urea: 61mg/dl; creatinine:
1.73mg/dl; normal ions; total protein:
4.4g/dl; albumin: 1.8g/dl; total cho-
lesterol: 295mg/dl, HDL: 61mg/dl,
LDL: 206mg/dl, triglycerides:
140mg/dl and normal hepatic enzyme
levels. Significant findings in the
urine analysis included proteinuria:
13.4g at 24h, 250 red blood cells per
microlitre and a negative leukocyte
count. The haemogram and coagula-
tion were normal, except for an FTP
of 762g/l. Autoimmunity assays: anti-
nuclear antibodies (ANA) and anti-
neutrophil cytoplasmic antibodies
(ANCA) negative; complement and
protein tests were normal. Serology
tests for hepatitis B (HBV), hepatitis
C (HCV) and human immunodefi-
ciency (HIV) viruses were negative.
Positive 1/32 titre RPR (rapid plasma
reagin) and FTA (anti-Treponema an-
tibody) results.
Renal ultrasound showed the kidneys to
be normal in size. The echocardiogram
was within normal limits and no lung
parenchyma changes were detected in the
chest X-ray.
letters to the editor
373 N efrologia 2011;31(3):358-78
syphilis appears months or years after in-
fection if it has not been properly treated.
In developed countries, largely due to the
discovery of penicillin, syphilis was prac-
tically wiped out in the 1950s.
4
In the
1980s, owing to the concern about the
AIDS epidemic, sexual behaviour changed
and an even greater decrease in its inci-
dence was observed. In recent years we
have been witnessing a resurgence of this
disease in Spain, with an increase in its in-
cidence from 2.57 cases per 100 000 in-
habitants in 1995 to 5.70 per 100 000 in
2008,
5
and this is also happening in other
European countries and the United States.
The new cases occur predominantly in
young homosexual men and a large pro-
portion of them present coinfection with
HIV (20%-70%, depending on the area in
question).
6
Perhaps this is due to a relax-
ation in sexual behaviour as a result of a re-
duction in protective measures following
the appearance of highly active antiretro-
viral therapy (HAART) against HIV.
4-7
Although the association between
syphilis and renal disease has been known
for over 100 years,
8
there are few cases re-
ported in Spain in reviews on the subject,
which makes diagnosis more difficult, as
it is seldom suspected in clinical practice.
Syphilis can cause a wide variety of
clinical and pathological forms of renal
disease. In addition to MGN, rapidly
progressive GN, diffuse endocapillary
GN with or without extracapillary for-
mation or minimal change GN have
been described.
8
Proteinuria is the most
common clinical manifestation. The de-
finitive diagnosis is confirmed by renal
biopsy.
It is important to know the age of the pa-
tient and to obtain a detailed clinical his-
tory when dealing with nephrotic syn-
drome. Although it is more common for
MGN to be associated with HBV than
syphilis, we must not forget that, in the
battery of serological tests requested in a
case of nephrotic syndrome, diagnostic
tests for syphilis should be included, more
so knowing that there has been a substan-
tial increase in the number of cases in
Spain in recent years.
Given that the data indicated a nephrotic
syndrome, a renal biopsy was performed
and 13 glomeruli were counted. They
were very slightly enlarged with perme-
able capillary lumens and no mesangial
proliferation or associated inflammatory
component. When Massons trichrome
procedure was used, frequent fuchsin-
stained deposits were observed on the
subepithelial side of the capillary walls.
With methenamine silver no spikes were
recognised. There was no increase in fi-
brous tissue in the interstitium. There were
areas of chronic inflammatory infiltration,
predominantly containing dispersedly dis-
tributed lymphocytes and eosinophils, lo-
cated around the glomerulus. The tubules
contained occasional hyaline cylinders
and haematic material. The blood vessels
were normal. Immunofluorescence re-
vealed intense granular IgG deposits on
the capillary walls and non-specific traces
of IgM. Anatomopathological diagnosis:
stage 1 MGN.
Treatment was initiated by administering
2.4 million units of intramuscular peni-
cillin G benzathine, intravenous diuretics,
and anti-thrombotic and lipid (choles-
terol)-lowering prophylactic drugs.
The patient responded favourably and
blood volume and renal function returned
to normal values (urea 43mg/dl, creati-
nine 1.28mg/dl) with a clearance rate of
85ml/min/1.73m
2
. At a check-up the fol-
lowing month the proteinuria had disap-
peared. 1/2 titre RPR values were ob-
tained at three months and they were
negative at six months.
Syphilis is a sexually transmitted disease
(STD) which is caused by a spirochete
called T. Pallidum. It can be transmitted
by sexual contact (the most common
form of transmission), congenitally via
the placenta, or as a result of an infected
blood transfusion or accidental inocula-
tion. It is known as the great simulator,
owing to its range of clinical presenta-
tions.
3
Primary syphilis manifests as an
ulcerated lesion or chancre, which ap-
pears two-six weeks after infection. Sec-
ondary syphilis is the result of its dissem-
ination via the blood or lymph and its
symptoms are highly varied. Tertiary
In our case, the patient had been diag-
nosed with syphilis before and its associ-
ation with nephropathy facilitated the ae-
tiological diagnosis of MGN. After
starting specific treatment (penicillin G
benzathine) to eliminate the triggering
factor, the nephrotic syndrome remitted.
This experience has made us see that it is
of vital importance to conduct a detailed
assessment when dealing with a case of
nephrotic syndrome. Once we have an ex-
act result and diagnosis, this will enable
us to adopt an economic, effective and,
above all, curative approach.
1. Registros glom erulonefritis por la Sociedad
Espaola de Nefrologa. Pam plona, 2009.
2. Satoskar AA, Kovach P, O Reilly K, Nadasdy T.
A n uncom m on cause of m em branous
glom erulonephritis. A m J Kidney D is
2010;55:386-90.
3. Lucas C osta A , Belinchn Rom ero I. La sfilis
hoy. Piel 2008;22:1-3.
4. Ibarra V, O teo JA . O tra vez la sfilis? M ed
Clin (Barc) 2003;120:295-6.
5. Servicio de Vigilancia Epidem iolgica. Centro
N acional de Epidem iologa. Vigilancia
epidem iolgica de las infecciones de
transm isin sexual 1995-2008, Feb 2010, 2-
6.
6. Sim m s I, Fenton K, A shton M , Turner KM E,
C raw ley-Boevey EE, G orton R, et al. The re-
em ergence of syphilis in the U nited
Kingdom : the new epidem ic phases. Sex
Trans Dis 2005;32:220-6.
7. M enndez B, Ballesteros J, C lavo P, D el
Rom ero J. A um ento de la sfilis y de la
infeccin genoccica en varones
hom osexuales o bisexuales en M adrid. M ed
Clin (Barc) 2005;125:756.
8. Hunte W , Al-G hraoui F, Cohen RJ. Secondary
syphilis and the nephrotic syndrom e. J A m
Soc Nephrol 1993;3:1351-5.
M.T. Mora Mora, M.S. Gallego Domnguez,
M.I. Castellano Cervio, R. Novillo Santana,
J.R. Gmez-Martino Arroyo
N ephrology D epartm ent.
H ospital of San Pedro de A lcntara. C ceres,
Spain
Correspondence: M.S. Gallego Domnguez
Seccin de N efrologa.
H ospital San Pedro de A lcntara. C ceres.
sgallegodom inguez@ hotm ail.com