Original
©2013 Dustri-Verlag Dr. K. Feistle
ISSN 0301-0430
DOI 10.5414/CN107863
e-pub: March 5, 2013
Received
August 14, 2012;
accepted in revised form
October 19, 2012
Correspondence to
Sultan Ozkurt, MD
Division of Nephrology,
Faculty of Medicine,
Eskisehir Osmangazi
University, Eskisehir,
Turkey
dr.s.guvenir@hotmail.com
Key words
nephrotic syndrome –
thromboembolic
complications – heredi-
tary thrombophilia
Assessment of genetic risk factors for
thromboembolic complications in adults with
idiopathic nephrotic syndrome
Melisa Sahin, Sultan Ozkurt, Nevbahar Akcar Degirmenci, Ahmet Musmul,
Gokhan Temiz and Mehmet Soydan
Division of Nephrology, Faculty of Medicine, Eskisehir Osmangazi University,
Eskisehir, Turkey
Abstract. Aims: Nephrotic syndrome
(NS) may occur with acquired hypercoagula-
bility, however, the fact that it is accompanied
by an underlying hereditary thrombophilia,
especially combined hereditary thrombo-
philia, would lead to thrombotic events. In
this study, we aimed to evaluate the contribu-
tion of genetic thrombophilia to development
of thrombotic events in adult patients with
NS. Material and methods: Factor V Leiden
(FVL), prothrombin, and methylenetetrahy-
drofolate reductase (MTHFR) gene mutation
were studied in 51 newly diagnosed idiopathic
NS patients and age- and gender-matched 20
healthy control subjects included in the study.
Renal vein Doppler ultrasound was conducted
in order to investigate the prevalence of sub-
clinical renal vein thrombosis. Results: Of 51
patients, 6 (11.8%) were established to have
thromboembolic (TE) complications at the
time of diagnosis (4 symptomatic, 2 subclini-
cal), and no recurring thrombotic episode was
observed. Genetic mutation was established in
all patients that were found to have TE com-
plications. Acquired hypercoagulability fac-
tors were similar in patients without and with
TE complication. Conclusions: The coexis-
tence of inherited thrombophilia in NS may
facilitate thromboembolic complications. If
the cause of thrombosis cannot be explained
by the usual factors attributed to the occur-
rence of thrombosis in NS, screening for the
other factors, such as FVL, MTHFR, and pro-
thrombin gene mutation, may be benefcial.
Introduction
The hemostatic system is activated in ne-
phrotic syndrome, with an increased tendency
toward thrombosis [1]. Abnormalities of the
coagulation system result from a complex in-
terplay between increased hepatic synthesis
and intravascular consumption of coagulation
factors and accelerated thrombin generation [1,
2]. The acquired hypercoagulability associated
with nephrotic syndrome could, however, coin-
cide with underlying inherited thrombophilia,
thereby resulting in a thrombotic event [3]. In
literature, there exists information as to the fact
that underlying genetic thrombophilia cause
earlier-presenting, life-threatening thrombotic
complications in the presence of such a facili-
tating factor as nephrotic syndrome [4, 5]. In
adult nephrotic syndrome patients, however,
the genetic aspect of thrombotic events has not
been studied much and was reported more like
case studies [6, 7]. Resistance to activated pro-
tein C, caused by a single-point mutation in the
Factor V gene (Factor V Leiden), has been re-
ported as the most common hereditary cause of
venous thrombosis [8]. This mutation has been
found in 30 – 60% of cases of familial throm-
bophilia and in 3 – 7% healthy people in two
White populations [9]. Among individuals with
inherited hyperhomocysteinemia, those homo-
zygous for methylenetetrahydrofolate reduc-
tase have elevated plasma homocysteine levels
and an important genetic risk factor for vascu-
lar disease [10]. The transition 20210G →A in
the 3’ untranslated region of the prothrombin
gene was associated with higher prothrombin
levels and with a threefold greater risk of ve-
nous thrombosis [11]. In this study, we aimed
to evaluate the contribution of genetic risk fac-
tors frequently observed for vascular thrombo-
sis in patients with adult nephrotic syndrome to
the development of thrombosis.
Patients and methods
The study was prospectively conducted
between January 2010 and December 2011
at the Nephrology Clinic of the Medical
Clinical Nephrology, Vol. 79 – No. 6/2013 (454-462)