What is the incidence of thromboembolic events in patients with nephrotic syndrome and hypoalbuminemia?

From the Guidelines

Thromboembolic events occur in approximately 20-30% of adult patients with nephrotic syndrome and low albumin levels, with the highest risk observed in those with albumin levels below 2.0 g/dL, particularly in patients with membranous nephropathy 1. The risk of thromboembolic events in patients with nephrotic syndrome and hypoalbuminemia is a significant concern, as it can lead to increased morbidity and mortality.

Key Factors

• The risk is particularly high in patients with membranous nephropathy, where the incidence can reach up to 37% 1.
• The risk increases significantly when serum albumin levels fall below 2.5 g/dL, with the highest risk observed in those with albumin levels below 2.0 g/dL 1.
• Renal vein thrombosis is the most common manifestation, but deep vein thrombosis, pulmonary embolism, and arterial thrombosis can also occur 1.

Pathophysiology

• The hypercoagulable state in nephrotic syndrome results from urinary loss of anticoagulant proteins (particularly antithrombin III), increased production of procoagulant factors by the liver, platelet hyperactivity, and hyperfibrinogenemia 1.

Management

• Prophylactic anticoagulation should be considered in patients with serum albumin below 2.0-2.5 g/dL, particularly those with membranous nephropathy or additional risk factors for thrombosis 1.
• Treatment doses of unfractionated or low-molecular-weight heparin or warfarin are the preferred agents for treatment or prevention in those felt to have thromboembolic risk greater than bleeding risk 1.
• Regular monitoring for symptoms of thrombosis is essential in all nephrotic patients with hypoalbuminemia 1.

Important Considerations

• Factor Xa inhibitors and direct thrombin inhibitors have significant/moderate albumin binding and are therefore lost in nephrotic urine, and pharmacokinetics are not well studied 1.
• Despite several favorable clinical case reports detailing the use of factor Xa inhibitors in the nephrotic syndrome, these popular agents are not recommended at this time 1.

From the Research

Incidence of Thromboembolic Events

• The incidence of thromboembolic events in patients with nephrotic syndrome and hypoalbuminemia is a significant concern, with studies suggesting an increased risk of thromboembolic complications 2, 3, 4, 5, 6.
• A study published in 2022 found that no patients experienced thromboembolic events during direct oral anticoagulant treatment, while five patients had a minor bleeding episode 2.
• Another study published in 2019 found that significantly more thromboembolic events were observed in the non-prophylactic anticoagulation group compared to the prophylactic anticoagulation group (4 versus 0 episodes, P = 0.035) 3.
• The risk of thromboembolism in nephrotic syndrome depends on various factors, including the severity and cause of nephrotic syndrome, with primary membranous nephropathy having the highest reported rates 4.
• Serum albumin concentration is an indicator for the risk of thrombosis in nephrotic syndrome patients, with a concentration of less than 25 g/l and at least one additional thrombogenic risk factor being a recommendation for primary prophylactic anticoagulation 5.

Risk Factors and Prophylaxis

• The severity of proteinuria and degree of hypoalbuminemia are common predictors of risk for thromboembolism in patients with nephrotic syndrome 6.
• Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with thromboembolic complications in patients with nephrotic syndrome 6.
• The duration of treatment and choice of therapeutic agent depend on several factors, including the degree of hypoalbuminemia, risk factors for thrombosis, and risk of bleeding 6.
• Prophylactic anticoagulation strategies for nephrotic syndrome currently rely on expert consensus opinion, such as in the recently published 2021 Kidney Disease Improving Global Outcomes glomerular disease guidelines 4.