Venous Thromboembolism in Primary Nephrotic Syndrome - Is the Risk High Enough to Justify Prophylactic Anticoagulation?

Abstract

Background: The reported incidence of venous thromboembolism (VTE) in patients with nephrotic syndrome (NS) varies widely, as does the approach to prophylactic anticoagulation. We aimed to assess the incidence of VTE in patients with primary NS in order to inform a sample size calculation to determine if a future clinical trial will ever be feasible. Methods: All adults undergoing native renal biopsy for NS between 2008 and 2013 yielding a diagnosis of primary glomerulonephritis were identified. Baseline serum albumin, urine protein:creatinine ratio, estimated glomerular filtration rate, date of biopsy and histological diagnosis were recorded. Episodes of objectively verified VTE were identified using the electronic patient record. Sample size calculations were performed based on 2 independent samples with a dichotomous outcome and to achieve a power of 80% and p < 0.05. Results: Two hundred six patients were included of which 60% were male and mean age at biopsy was 55 years (SD 19). Median follow-up was 2.9 years (interquartile range (IQR) 1.6-4.7). Fourteen (6.8%) patients suffered VTE. Median time to diagnosis of VTE from renal biopsy was 36 days (IQR -22 to 178), with 6 VTEs occurring prior to biopsy and 1 during remission. In a total of 270 patient years of NS, there were 7 VTE that could potentially have been avoided if anticoagulation was given for the duration of NS, that is, 2.6% risk per year of NS; this risk was highest for patients with minimal change nephropathy at 13.3% per year of NS, compared to 0.65% per year of NS for those with idiopathic membranous nephropathy. Assuming a 75% reduction in the incidence of VTE with prophylactic anticoagulation, 972 participants would be required for a future clinical trial to have 80% power. Conclusions: Patients with primary NS are at an increased risk of VTE. The timing of VTE means that only half of episodes would be targeted by prophylactic anticoagulation. Given the low frequency of events, a well-powered clinical trial would be challenging to achieve.

Nephrotic syndrome with acute pulmonary embolism in young adults

“…Though there is no guidelines or consensus on the prevention with anticoagulants in patients with nephrotic syndrome, but the study suggested the patients with nephrotic syndrome and combined with hypercoagulation should receive anticoagulants therapy to prevent thrombotic events. [ 15 ] We look forward to the well-powered clinical trials to be achieved.…”

Should We Screen Patients with Unprovoked Venous Thromboembolism for Hyperthyroidism? Report of Several Paradigmatic Clinical Cases from the RIETE Registry

“…According to this defi nition several studies record a nearly 40-50% of unprovoked VTE in real life [5] and according to common thrombotic risk factors suggested by guidelines 2014; yet other clinical conditions are well known as conditions that may predispose for VTE as infl ammatory bowel disease, immunopathological disease and/or connectivitis, nephritic syndrome and others [10][11][12].…”

“…However, the literature does not offer the chance to understand the percentage of other medical condition associated to VTE as minor thrombotic risk factor such as infl ammatory bowel diseases [10], immunopathological disease/connectivitis [11], hormonal disease including hyperthyroidism [17] and so on.…”

“…However, several other clinical conditions may be associated with VTE but, are not usually considered for daily screening as a potential cause of VTE, nor are reported as common cause of VTE in large randomized clinical trials and registries including nephrotic syndrome, infl ammatory bowel disease, connectivitis and others [10][11][12].…”

Direct-Acting Oral Anticoagulants as Prophylaxis Against Thromboembolism in the Nephrotic Syndrome

“… 2 However, although the thrombotic risk is congruous across different samples and studies, the absolute risk estimates for thrombosis appear to vary by study cohort, both overall and by primary form of glomerulonephritis. 20 , 21 Risk also appears to vary by duration of NS, age, etiological glomerular condition (membranous nephropathy being highest risk), personal thrombosis history, degree of proteinuria, central venous catheterization, and coexisting maliganancy. 2 , 21 , 22 Thrombosis appears to be highest risk in the first 6 months of diagnosis or presentation; however, it may occur at any stage.…”