Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in patients with idiopathic membranous nephropathy: an observational study

Abstract

BackgroundPatients with nephrotic syndrome are at an increased risk of thromboembolic events (TEs). However, this association has not been thoroughly investigated in adult patients with idiopathic membranous nephropathy (IMN).MethodsA retrospective analysis of all 101 consecutive adult patients with MN diagnosed at our centre during 1995 to 2008 was performed. Pertinent data including thromboembolic events and the risk factors for TEs were recorded.ResultsThe cohort was followed for 7.2 ± 3 years. Out of 78 patients with IMN, 15 (19.2%) had at least one TE. No TEs occurred six months after diagnosis. The incidence of TEs in the first 6 months of diagnosis was 7.69% (95%CI, 2.5-17.0) and all patients except one had venous TEs. At the time of diagnosis of MN, the patients with TEs had lower serum albumin (1.9 ± 0.5 vs. 2.4 ± 0.4 g/dl, TE vs. no TE; p < 0.01) and greater serum cholesterol (414 ± 124 vs. 317 ± 108 mg/dl, TE vs. no TE; p = 0.01) and 24-h proteinuria (10.7 ± 3 vs. 7.1 ± 4 g, TE vs. no TE; p < 0.01). Multivariate logistic regression adjusted for age, sex, cholesterol and creatinine revealed, an odds ratio of 0.8 (95% CI 0.7 – 0.96; p = 0.01) for every one g/dl increase in baseline serum albumin and, an odds ratio of 1.3 (95% CI 1.05-1.58; p = 0.01) for one gram increase in 24-h proteinuria, for TEs.ConclusionsOur study finding confirms IMN as a prothrombotic state particularly in the first six months of diagnosis. Proteinuria, in addition to hypoalbuminemia, is a risk factor for TEs. These results have important implications for clinical care of patients with IMN, particularly with regards to initiation and duration of prophylactic anticoagulation.

Mechanisms of hypercoagulability in nephrotic syndrome associated with membranous nephropathy as assessed by thromboelastography

“…This result confirms previous findings in the literature [15] and suggests a need to strengthen efforts to prevent hypercoagulable state, especially for MN patients with severe hypoalbuminemia. Because of the relatively low correlation coefficient between CI and 24-hour urinary protein excretion, we could not clearly demonstrate urine protein as a risk factor for hypercoagulability [16].…”

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

“…[58][59][60] However, both serum albumin and proteinuria severity have been epidemiologically linked to thrombotic risk. [13][14][15][16][17][18] Thus, if confirmed, proteinuria and/or serum Figure 5. In vivo coagulation is not activated de novo in the setting of massive proteinuria but is more robust when stimulated during PAN nephrosis.…”

“…[10][11][12] Recent epidemiologic studies have revealed that both proteinuria and serum albumin may be associated with the likelihood of thrombosis, with higher proteinuria and lower serum albumin correlating with increased thrombotic risk, suggesting that disease severity may be directly correlated with the severity of coagulation system derangement. [13][14][15][16][17][18] Thus, determining the relationship between hypercoagulopathy and these markers of disease severity may lead to the identification of clinically meaningful urine protein and/or serum albumin levels beyond which prophylaxis with anticoagulants may be warranted.…”

Predictive factors for effectiveness and safety of enoxaparin for total knee arthroplasty in aged Japanese patients: a retrospective review

“…Additionally, hypoalbuminemia is a major complication after surgery, including TKA [25–27]. Kumar et al [28] reported that hypoproteinemia is a risk factor for DVT. These findings suggest that hypoproteinemia is indirectly associated with the efficacy of enoxaparin.…”

“…However, our data lacked information about serum albumin levels, so we could not completely clarify a potential mechanism for serum total protein affecting the effectiveness and safety of enoxaparin. As discussed above, hypoproteinemia seems to be independently associated with the induction of DVT and indirectly affects the efficacy of enoxaparin [28]. Further studies will be needed to identify the pharmacokinetics and pharmacodynamics of enoxaparin in patients with and without hypoalbuminemia.…”