Young man with nephrotic syndrome and portal vein thrombus successfully treated with edoxaban − case report
Venous thrombosis is one of the main complications of nephrotic syndrome (NS), though it is most often located in the renal vein. The following case report describes an adult patient with relapsing corticosteroid-dependent minimal change disease complicated by portal vein thrombosis and subsequent successful treatment with edoxaban.
Previous case development
A 38-year-old patient with nephrotic syndrome, presenting among other symptoms with anasarca and a 14 kg weight gain, was referred to the nephrology department of the Tokushima University Hospital in Japan. Based on a renal biopsy, he was diagnosed with minimal change disease. The patient was treated with corticosteroids until complete remission was achieved and subsequently was regularly monitored at the department.
Relapse of nephrotic syndrome
However, 4 years later, he was hospitalized again for bilateral lower limb edema with a weight gain of about 10 kg in the past month.
Initial examination provided the following results:
- Physical examination: TT 36.1°C, BP 121/77 mmHg, RR 20/min, HR 84/min
- Laboratory examination: total protein 37 g/l, serum albumin 13 g/l, total cholesterol 10.1 mmol/l, urinary protein/creatinine ratio approx. 1710 mg/mmol, serum urea 4.3 mmol/l, creatinine 64.5 µmol/l
Given the clinical symptoms and laboratory results, recurrence of nephrotic syndrome was suspected. Therefore, pulse corticosteroid therapy was initiated at a dose of 1 g methylprednisolone/day for 3 days, followed by oral prednisolone at a dose of 45 mg/day.
Complications during hospitalization
After 19 days of therapy, routine blood tests showed ALT and AST levels twice the upper limit of normal, with GGT reaching 15.2 µkat/l. While initial suspicion was drug-induced liver injury, which is a common cause of mild aminotransferase elevation during immunosuppressive or steroid therapy, the combination of nephrotic syndrome in the patient's history and elevated liver enzymes led clinicians to consider other possible causes.
Abdominal ultrasound revealed extensive portal vein thrombosis, which was confirmed by CT scan. No pathologies were observed in the kidneys, liver, inferior vena cava, renal, or subhepatic veins. Coagulation parameters were relatively normal: PT (Quick) 10.3 s, INR 0.85, aPTT 26.6 s, antithrombin III 94.2%, protein C 214%, protein S 82%.
Immediate anticoagulation therapy with edoxaban at a dose of 30 mg/day orally was initiated. It was discontinued after 2 months when complete remission of nephrotic syndrome was achieved (proteinuria < 300 mg/day). Follow-up CT and regular abdominal ultrasounds showed no visible thrombus.
Discussion and conclusion
Portal vein thrombosis is a rare complication of nephrotic syndrome. Its diagnosis is challenging due to nonspecific symptoms and should be considered especially when liver enzymes are elevated.
Currently, anticoagulants (primarily unfractionated or low-molecular-weight heparin, synthetic polysaccharides, and warfarin) are recommended for treating portal vein thrombosis, aside from addressing the triggering cause (likely NS in combination with pharmacotherapy using glucocorticoids and diuretics, and immobilization in this case). Less commonly, thrombolytics, thrombectomy, or transjugular intrahepatic portosystemic shunt (TIPS) implantation are considered. Laboratory monitoring is essential when treating with unfractionated heparin during hospitalization, with a risk of heparin-induced thrombocytopenia. Warfarin poses a high bleeding risk, requires gradual INR-titrated dosing, and problematic dosing in patients with liver insufficiency. Although low-molecular-weight heparin is generally safe, subcutaneous administration can be difficult in patients with anasarca or ascites, as subcutaneous edema can impair absorption.
This case report points to the potential successful use of edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), in treating portal vein thrombosis associated with NS. However, due to the lack of clinical studies evaluating its efficacy and safety for this diagnosis, it is not yet routinely used.
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Source: Obata F., Abe H., Murakami T. et al. Direct oral anticoagulant successfully used to treat an adult nephrotic patient complicated with portal vein thrombosis. CEN Care Rep 2019; 8 (2): 134−138, doi: 10.1007/s13730-019-00381-9.
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