Nephrotic syndrome and risk of venous and arterial thromboembolism

December 30, 2007 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

Overview
Groningen Patients with nephrotic syndrome are at risk for venous (VTE) and arterial thromboembolism (ATE), however the absolute risk of these events was not clearly defined. A retrospective study of patients with nephrotic syndrome has found that the annual incidence of was 1.02% for VTE and 1.48% for ATE.

The investigators performed a retrospective analysis of 298 consecutive patients with nephrotic syndrome, with mean follow-up of 10 years. For almost all patients, nephrotic syndrome was defined by a 24-hour urine protein > 3.5 grams. Thromboembolic events were considered only if objective evidence was available. A variety of risk factors for atherosclerosis or coagulopathy were gleaned from the medical records, as were serum levels of albumin, cholesterol, triglycerides, and creatinine.

The mean patient age was 41, 59% were male, 10% had a thromboembolic event prior to the diagnosis of nephrotic syndrome. The causes of nephrotic syndrome were well-distributed: 24% had membranous glomerulopathy, 16% had minimal change disease, 12% with FSGS, 11% focal segmental glomerulosclerosis, 9% membranoproliferative glomerulonephritis, 11% diabetic nephropathy, and 28% had nephrotic syndrome not otherwise specified.

Overall, the annual incidence 1.02% for VTE and 1.48% for ATE. Calculated over the first 6-months, the annual incidence was 9.85% and 5.53%, respectively. The VTE risk was lowest among patients with diabetic nephropathy (0.58%) and highest in patients with membranous glomerulopathy (1.4%). Arterial thromboembolic events, however, were highest in the patients with diabetic nephropathy (7.43% annual incidence). Low serum albumin (<2.4 g/dL; HR 2.6) and high proteinuria (>8.2 g/day; HR 5.2) were associated with increased risk of VTE, however the ratio of proteinuria to serum albumin was a better predictor or VTE risk (HR 5.6, CI 1.2 to 26.2, p = 0.03). Neither proteinuria nor hypoalbuminemia predicted ATE. Atherosclerotic risk factors - diabetes, age, sex, hypertension, smoking, previous ATE and high creatinine - predicted risk for ATE.

This study demonstrated a high absolute risk of VTE and ATE in patients with nephrotic syndrome. Interestingly, the risk was highest in the 6-months following diagnosis, and the authors suggest that this knowledge might warrant thromboprophylaxis. The lack of association between proteinuria and ATE risk is also of note, as there has been much talk lately of the linear correlation between microalbuminuia below the level of detection by routine urinalysis and coronary heart disease risk.

1. Mahmoodi BK, Ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L, Navis G, van der Meer J. High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome. Results From a Large Retrospective Cohort Study. ''Circulation. 2007 Dec 24; [Epub ahead of print]'' PMID: 18158362