Renal vein thrombosis
 Patients with the nephrotic syndrome
are at increased risk of developing
venous and arterial
thromboembolism, particularly RVT
 The mechanism of thromboembolism
in nephrotic syndrome and optimal
diagnostic and anticoagulant
management strategies remain
controversial
Prevalence of renal vein thrombosis according to
underlying disease in nephrotic syndrome
Study
Membranous GN
MPGN
MCD
FSGS
Other
Overall
Llach, et al. Am J Med
1980
29.0 (69)
22.2 (27)
20.0 (10)
25.0 (4)
9.8 (41)
21.9 (151)
Chugh, et al. Postgrad
Med J 1981
42.9 (7)
20.0 (5)
26.3 (19)
0 (5)
25.0 (8)
25.0 (44)
Velasquez, et al. Am J
Nephrol 1988
60.0 (5)
40.0 (10)
0 (0)
28.6 (7)
50.0 (4)
42.3 (26)
Wagoner, et al. Kidney
Int 1983
51.9 (27)
0 (0)
0 (0)
0 (0)
0 (0)
51.9 (27)
Bennett, et al. Ann
Intern Med 1975
–
–
–
–
–
28.6 (21)
Overall
37.0 (108)
26.2 (42)
24.1 (29)
18.8 (16)
15.1 (53)
27.9 (269)
Singhal et al, Thrombosis Research (2006) 118, 397—407
 A retrospective study involving 298
patients with mean follow up of 10
years showed annual incidences of
VTE and ATE of 1.02% and 1.48%
respectively
 Risks of both VTE and ATE were
particularly high within the first 6
months of NS (annual incidences
9.85% and 5.52% respectively)
Mahmoodi et. Al Circulation. 2008 Jan 15;117(2):224-30
Clinical features
 RVT may be unilateral or bilateral and
may extend into the inferior vena cava
 RVT most often has an insidious onset
and produces no symptoms referable
to the kidney
 Acute RVT is usually due to trauma, severe
dehydration or a generalized hypercoagulable
state
 It typically presents with symptoms of renal
infarction, including flank pain, microscopic
or gross hematuria, a marked elevation in
serum lactate dehydrogenase, and an
increase in renal size on radiographic study
 Bilateral RVT may present with acute renal
failure
Pathogenesis
Increased platelet aggregation
 Thrombocytosis, decreased red blood cell
deformability, and increased von Willebrand
factor levels in NS favor platelet transport
towards the vessel wall and increase
platelet adhesion
 Hypoalbuminemia results in increased
availability of normally albumin-bound
arachidonic acid, leading to increased
formation of thromboxane A2 in platelets, a
stimulus for platelet aggregation
 Elevated levels of LDL cholesterol may
increase platelet aggregation
Activation of the coagulation
system
 Patients with nephrotic syndrome
demonstrate urinary loss of plasma proteins
that include factors IX, X, and XII,
prothrombin, antithrombin, and α2antiplasmin
 In contrast, proteins of higher molecular
weight, including factor V, factor VIII, von
Willebrand factor, fibrinogen, and α2macroglobulin accumulate, presumably
because of increased synthesis
 Factor VIII levels are typically increased as
much as 2- to 3-fold compared to controls and
increased factor VIII may be a risk factor for
venous thromboembolism
 There is an inverse correlation between serum
albumin and fibrinogen levels in nephrotic
syndrome
 Hyperfibrinogenemia may contribute to the
procoagulant state by providing more substrate
for fibrin formation and by promoting platelet
hyperaggregability, increased blood viscosity,
and red blood cell aggregation
Decreased endogenous
anticoagulants
 Antithrombin deficiency occurs in 40% to
80% of patients with NS
 Plasma levels of antithrombin correlate
negatively with proteinuria and positively
with serum albumin level, presumably due
to urinary loss of this factor
 The association between antithrombin
deficiency and venous thromboemolism is
inconsistent among different studies
Additional factors predisposing to
thromboembolism in NS
 Intravascular volume depletion and
exposure to steroids
 Loss of fluid across the glomerulus causing
hemoconcentration in the postglomerular
circulation which is worsened by diuretic
therapy
 Clotting activation and thrombin formation
might occur in the diseased kidney
 The nature of immunologic injury itself
Factors reported to be associated with RVT in the
absence of nephrotic syndrome
 Trauma (including kidney biopsy)
 Oral contraceptives
 Hypovolemia
 Inherited procoagulant defects
Screening
Routine screening for RVT is not
recommended in patients with nephrotic
syndrome
No proven benefit to diagnosing occult
disease
A patient with a negative study may
develop RVT at a later time
It is also not useful to evaluate for RVT in a patient who
experiences an overt embolic event such as PE
It cannot be proven that the pulmonary embolus
originated in the renal veins
In situ pulmonary thrombosis may occur
Patients will be treated with anticoagulants whether or
not RVT is present
Diagnosis
 Estimated sensitivity and specificity of CT with
contrast was 92.3% and 100%, respectively
 Only a small number of studies have evaluated the
value of MRI with or without contrast enhancement in
the identification of RVT
 Only one study has prospectively evaluated Doppler
ultrasonography in the diagnosis of RVT and found it
to be 85% sensitive and 56% specific
 Intravenous pyelography was found to have a
sensitivity of 34.1% and a specificity of 87.2%
 Selective renal venography is the reference standard
diagnostic test for RVT
Treatment
 The risks associated with asymptomatic
RVT have not been compared to the risks of
long term anticoagulation therefore
prophylactic anticoagulation is not
recommended
 There are no definitive studies that have
evaluated the role of anticoagulation in
patients with an asymptomatic RVT, but
case series report treating such patients
 Patients with a symptomatic RVT or a thromboembolic
event in the absence of RVT are treated with low
molecular weight heparin and then warfarin
 Some patients are partially resistant to heparin
therapy due to severe antithrombin deficiency
 Warfarin therapy is given for a minimum of 6 to 12
months and some people recommend continuing
treatment for as long as the patient remains nephrotic
 Local thrombolytic therapy with or without
thrombectomy in patients who have signs of acute
RVT has been successfully performed in small
numbers of patients
Can renal vein thrombosis cause the
nephrotic syndrome?
 Animal studies in which main renal vein
occlusion was produced experimentally,
have failed to demonstrate the
development of heavy proteinuria unless
the contralateral normal kidney is removed
 RVT in the absence of nephrotic syndrome
has been reported in the literature
 Nephrotic patients with RVT who have
undergone histologic evaluation show
evidence of an identifiable glomerulopathy
 In a case report of a patient with unilateral
RVT and nephrotic syndrome due to
membranous nephropathy, bilateral ureteral
catheterization studies showed no
difference in protein excretion or creatinine
clearance between the two kidneys
 In retrospective studies, the sequence of
nephrotic syndrome leading to renal vein
thrombosis was clearly established
 However bilateral RVT has been reported to
cause nephrotic syndrome
References
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Radhakrishnan, J. Renal vein thrombosis and hypercoagulable state in
nephrotic syndrome. Uptodat May 2009
Singhal, R, Brimble, KS. Thromboembolic complications in the
nephrotic syndrome: Pathophysiology and clinical management.
Thromb Res 2006; 118:397
F. Llach, S. Papper and S.G. Massry, The clinical spectrum of renal vein
thrombosis: acute and chronic, Am J Med 69 (1980), pp. 819–827
K.S. Chugh, N. Malik, H.S. Uberoi, V.K. Gupta, M.L. Aggarwal and P.C.
Singhal et al., Renal vein thrombosis in nephrotic syndrome—a
prospective study and review, Postgrad Med J. 57 (1981), pp. 566–570
F.F. Velasquez, P.N. Garcia and M.N. Ruiz, Idiopathic nephrotic
syndrome of the adult with asymptomatic thrombosis of the renal vein,
Am J Nephrol 8 (1988), pp. 457–462
R.D. Wagoner, A.W. Stanson, K.E. Holley and C.S. Winter, Renal vein
thrombosis in idiopathic membranous glomerulopathy and nephrotic
syndrome: incidence and significance, Kidney Int 23 (1983), pp. 368–
374
W.M. Bennett, Renal vein thrombosis in nephrotic syndrome, Ann
Intern Med 83 (1975), pp. 577–578
References
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