Regular ArticleThromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management
Introduction
The nephrotic syndrome, first described in 1827 [1], is defined by a urinary protein level exceeding 3.5 g/l.73 m2/day occurring in association with edema, hypoalbuminemia, hyperlipidemia, and infectious and thromboembolic complications [2]. Thromboembolic disease is an important complication in patients with nephrotic syndrome, as both arterial and venous complications occur and the consequences are often severe. On the other hand, many patients are asymptomatic, leading to difficulties in establishing the diagnosis and with controversy existing regarding the role of prophylactic anticoagulant therapy. Much evidence suggests that a hypercoagulable state exists in the setting of the nephrotic syndrome, but the exact mechanisms are poorly understood [2].
In this review, we shall discuss the epidemiology and clinical spectrum of thromboembolic disease occurring in the nephrotic syndrome, the pathophysiology of the hypercoagulable state observed in the nephrotic syndrome, the diagnosis of renal vein thrombosis (RVT) in nephrotic syndrome, and the evidence supporting prophylactic and therapeutic anticoagulation for these thromboembolic disorders.
Section snippets
Etiology of the nephrotic syndrome and risk renal vein thrombosis
Venous thromboembolic complications in nephrotic syndrome include deep venous thrombosis, pulmonary embolism and, in particular, RVT. Early observations led researchers to believe that renal vein obstruction itself led to the development of nephrosis [3], [4], [5]. However, advanced roentgenographic techniques and renal vein catheterization have made it clear that RVT is a consequence of the nephrotic syndrome [6], [7], [8].
Nephrotic syndrome of any etiology can be associated with RVT.
Hypercoagulability in patients with the nephrotic syndrome
Maintenance of hemostasis involves a number of processes, including formation of a platelet plug through platelet activation and aggregation, activation of the clotting cascade, initiated by exposure of tissue factor at sites of vessel wall injury, termination of the clotting cascade through a variety of inhibitors, and dissolution of the formed clot via plasmin (fibrinolysis). Abnormalities in any of the steps that promote coagulation may lead to thrombosis. Thrombosis in nephrotic syndrome
Diagnosis of renal vein thrombosis
Selective renal venography is the reference standard diagnostic test for RVT, with demonstration of a persistent filling defect in the renal veins [12], [82]. However, renal venography is invasive, and is associated with complications that include pulmonary embolism due to clot dislodgement, inferior vena cava perforation, and contrast-induced acute renal failure [10]. Consequently, renal venography is not widely used, and non-invasive diagnostic tests which are discussed below are preferred to
Antithrombotic therapy for renal vein thrombosis
Numerous antithrombotic approaches have been assessed for the treatment of RVT. The first reports of successful thrombectomy for bilateral RVT [99] and thrombolysis [100] emerged 35 years ago. Shortly thereafter, in 1972, warfarin was used successfully for unilateral RVT, and anticoagulation was proposed as standard therapy for chronic RVT [101]. Since then, warfarin has been found to be an effective therapy for the prevention and treatment of a broad spectrum of thromboembolic disorders [29],
Prophylactic anticoagulation in patients with the nephrotic syndrome
Controversy exists regarding the use of prophylactic anticoagulation therapy in patients with nephrotic syndrome who do not have RVT or those with a prior history of venous thromboembolism. The high incidence of venous thromboembolism in patients with the nephrotic syndrome suggests a possible role for prophylactic anticoagulant therapy. In view of the higher risk of thromboembolic complications in patients with membranous glomerulonephritis, prophylactic anticoagulation has been suggested for
Summary
The nephrotic syndrome is complicated by the induction of a hypercoagulable state and various venous and arterial thromboembolic phenomena. RVT is the most common of these findings, is usually asymptomatic, and is most commonly identified in patients with membranous glomerulopathy. Untreated RVT can predispose to serious sequelae such as pulmonary embolism, and once identified, should be treated with anticoagulation.
Although many derangements in the hemostatic system have been described in the
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