High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome

Abstract

Background-No data are available on the absolute risk of either venous thromboembolism (VTE) or arterial thromboembolism (ATE) in patients with nephrotic syndrome. Reported risks are based on multiple case reports and small studies with mostly short-term follow-up. We assessed the absolute risk of VTE and ATE in a large, single-center, retrospective cohort study and attempted to identify predictive factors in these patients. Methods and Results-A total of 298 consecutive patients with nephrotic syndrome (59% men; mean age, 42Ϯ18 years)were enrolled. Mean follow-up was 10Ϯ9 years. Nephrotic syndrome was defined by proteinuria Ն3.5 g/d, and patients were classified according to underlying histological lesions accounting for nephrotic syndrome. Objectively verified symptomatic thromboembolic events were the primary study outcome. Annual incidences of VTE and ATE were 1.02% (95% confidence interval, 0.68 to 1.46) and 1.48% (95% confidence interval, 1.07 to 1.99), respectively. Over the first 6 months of follow-up, these rates were 9.85% and 5.52%, respectively. Proteinuria and serum albumin levels tended to be related to VTE; however, only the predictive value of the ratio of proteinuria to serum albumin was significant (hazard ratio, 5.6; 95% confidence interval, 1.2 to 26.2; Pϭ0.03). In contrast, neither the degree of proteinuria nor serum albumin levels were related to ATE. Sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate predicted ATE (PՅ0.02). Conclusions-This study verifies high absolute risks of symptomatic VTE and ATE that were remarkably elevated within the first 6 months. Whereas the ratio of proteinuria to serum albumin predicted VTE, estimated glomerular filtration rate and multiple classic risk factors for atherosclerosis were predictors of ATE. (Circulation. 2008;117: 224-230.)

Venous Thromboembolism in Patients with Membranous Nephropathy

“…The clinical impact of undetected asymptomatic VTE is not known, and the frequency and location of VTEs are highly dependent upon the modality and intensity of clinical screening. In our population, RVT accounted for 30% of VTEs, in the range previously reported (13%242%) (5,(18)(19)(20). However, other studies using systematic screening venography reported higher proportions of RVT (50%280%) (2,4).…”

“…Arterial thromboses are predominantly cardiac and cerebrovascular events (20), which are common in the general population, are largely attributable to atherosclerosis or atrial fibrillation, and are greatly affected by traditional cardiovascular risk factors. As a result, determining the independent risk of arterial thrombotic events attributable to the nephrotic syndrome would require a careful assessment of the incidence ratio compared with a control population matched for age, sex, race, blood pressure, and smoking.…”

Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

“…[26][27][28][29] The association between low serum albumin and risk of VTE has been previously described in nephrotic syndrome. 11,12,14,30 Serum albumin is inversely correlated with the degree of urinary protein loss, and may be a surrogate marker for loss of endogenous antithrombotic proteins such as antithrombin III and plasminogen. Serum albumin levels may have direct effects on hemostasis and platelet aggregation 26 and in addition levels may be decreased in critical illness and thus correlate with more advanced disease.…”

“…The nephrotic syndrome, a common presentation of AL, is associated with hypercoagulability and may contribute to the risk of venous thromboembolism (VTE) in this population. [10][11][12][13][14][15] Other potential contributors to thromboembolic risk include monoclonal gammopathy and plasma cell dyscrasia 16 as well as AL treatments, specifically immunomodulatory agents (IMiDs) [17][18][19][20][21][22][23] and those requiring central venous catheters. A means of risk stratification of VTE in this population is needed to guide prophylaxis and treatment strategies.…”

The Treatment of Minimal Change Disease in Adults

“…25,26 Given the risk of adverse events caused by current treatment modalities, one may ask whether MCD patients should be treated or not. However, the significant comorbidities associated with NS (hyperlipidemia, 27 infections, 16,28 skin breakdown from edema, risk of thromboembolic events, 29,30 AKI, and worsened quality of life) prompt most physicians to recommend treatment for MCD patients. Importantly, drug-related adverse events become more common in FR and SD patients because of prolonged and repeated exposure to corticosteroids.…”