Victoria Socha

DocwireNews

Primary 
membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. 
Therapy for primary MN focuses on the prevention of end-stage renal disease 
(ESRD). ESRD commonly occurs several years following presentation with primary 
MN; however, other complications may occur much earlier in the course of the 
disease.Early 
complications of primary MN include venous thromboembolic events (VTEs) such as 
deep venous thrombosis (DVT), renal vein thrombosis (RVT), and pulmonary 
embolism (PE). These complications are associated with significant morbidity 
and mortality. Hypoalbumineia is the most significant indicator of risk of VTE. 
Patients with primary MN also experience increased high absolute risk of 
arterial thromboembolic events (ATEs) within 6 months of presentation. 
Predictors of ATEs include severe proteinuria, estimated glomerular filtration 
rate, and smoking. Primary cardiovascular events include acute coronary 
syndrome (ACS) and ischemic stroke (IS).Given the need to 
carefully manage anticoagulants and antiplatelet agents and to tailor 
therapeutic regimens to an individual&rsquo;s risk of thromboembolic events, the 2012 
Kidney Diseases Improving Global Outcomes (KDIGO) evidence supporting 
prophylactic and therapeutic anticoagulation is, according to researchers, too 
weak to meet the needs of primary MN patients with hypoalbuminemia. Honghong 
Zou and Yebei Li, PhD, conducted a review to provide suggestions to 
help guide decision making on the management of anticoagulation in patients 
with primary MN at high risk of thrombosis or with thromboembolic 
complications. Results of the review were reported online in BMC Nephrology.The researchers 
extracted relevant studies by searching the Cochrane Library, Medline, PubMed, 
and Web of Science from March 1968 to March 2018. Eligible publications 
included guidelines, reviews, case reports, and clinical trial studies 
regarding the rational management of anticoagulation therapy in the primary MN 
population.The review 
demonstrated that the risk of thromboembolic events is particularly high in 
primary MN when compared with other pathological types of nephrotic syndrome 
and that most patients remain asymptomatic. This finding suggests considering 
the prophylactic use of anticoagulants or antiplatelet agents to prevent VTEs 
and ATEs in this patient population. The findings also suggest that the 
rational management of therapeutic anticoagulation and antiplatelet agents in 
patients with primary MN and thromboembolic complications may result in the 
reduction in the risk of recurrent cardiovascular events.Low serum albumin 
is a strong independent risk factor for VTEs in patients with primary MN. The 
increasing risk was proportionally associated with declining albumin levels in 
a retrospective study accessed by the review. There was an association between 
each 1.0-g/dL increase in albumin level and a 2.13-fold increase risk of VTE. 
The study identified the threshold albumin level for the overall risk of VTEs 
as 2.8 g/dL (i.e., a serum albumin level &lt;2.8 g/dL indicated a high risk of 
a VTE). In another study, anticoagulation was indicated in patients with 
primary MN who initially presented with thrombotic events due to the high risk 
of thromboembolic complications. However, the use of prophylactic 
anticoagulation therapy remains controversial in primary MN.The 2012 KDIGO 
guidelines indicate that prophylactic oral warfarin can be considered in 
primary MN patients when serum albumin is &lt;2.5 g/dL in the presence of 
additional risks for thrombosis; some physicians believe prophylactic 
anticoagulation should be initiated earlier. Studies have shown that aspirin 
has a therapeutic benefit for the prevention and recurrence of VTEs and 
significantly reduces the rate of major vascular events with no apparent 
increase in the risk of major bleeding. Some of the researchers in the reviewed 
studies felt that patients with primary MN could receive antiplatelet agents 
such as aspirin for the primary prevention of thrombotic events at an early 
stage of the disease.The studies also 
indicated that the benefits of anticoagulation in the prevention of VTEs should 
be weighed against the risk of hemorrhage complications in individual patients. 
Researchers in one study developed a Markov-based decision analysis model to 
estimate the possibility of benefit based on an individual&rsquo;s bleeding risk 
profile, serum albumin level, and acceptable benefit-to-risk ratio.The treatment 
regimen for thromboembolic complications in patients with primary MN was 
similar to that in patients in the general population with thromboembolic 
events. D-dimer level may be affected by proteinuria and may not be an 
independent predictor of stopping anticoagulant therapy in patients with 
primary MN and VTEs. Further, the reduction of proteinuria and the increase of 
serum albumin are important goals for the treatment of primary MN with VTEs. 
Clinicians should continue the previous steroid therapy or combine it with 
immunosuppressive agents over the entire treatment period until the primary MN 
treatment protocol is completed. There are no clinical trial data regarding the 
optimal length of anticoagulation therapy in this patient population; one 
potential approach is to treat patients with anticoagulation therapy at least 3 
to 6 months (if there are no contraindications) until serum albumin levels 
normalize and patients achieve remission.The researchers 
cited some limitations to the review, including the majority of the evidence 
for prophylactic anticoagulation recommendations being derived from retrospective 
studies.&ldquo;The utility of 
prophylactic aspirin or warfarin may have clinical benefits for the primary 
prevention of thromboembolic events in primary MN patients with 
hypoalbuminemia,&rdquo; the researchers said. &ldquo;It is necessary to perform large 
randomized controlled trials and to formulate relevant guidelines to support 
the present review,&rdquo; they added.Takeaway 
Points<ol class="wp-block-list">
<li>Patients with primary membranous nephropathy (MN) 
are at increased risk for thromboembolic complications, including venous thromboembolic 
events (VTEs).</li>
<li>Researchers conducted a literature review to 
provide suggestions on decision making regarding anticoagulant management in 
patients with primary MN at high risk of thrombosis or with thromboembolic 
complications.</li>
<li>The use of prophylactic aspirin or warfarin may 
have clinical benefits for the primary prevention of thromboembolic events in 
patients with primary MN with hypoalbuminemia.</li>
</ol>

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