1 “Carol Davila” University of Medicine and Pharmacy, Department of Nephrology, Urology, Transplant Immunology, Dermatology and Allergology, Str. Dionisie Lupu Nr. 37, Sector 1, 020021, Bucharest, Romania, Tel: 0722792429
2 Department of Nephrology, Urology, Transplant Immunology, Dermatology and Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3 Department of Nephrology, “Ovidius” University of Medicine and Pharmacy, Constanta, Romania
Background: The nephrotic syndrome (NS) is associated with an increased incidence of thromboembolic complications due to multiple abnormalities in haemostasis and the coagulation system occurring in these patients. We aimed to assess prospectively the risk of venous thromboembolic events (VTE) in a large cohort of NS patients and to identify predictive factors for VTE, especially haemostasis-related parameters. Methods: We performed a prospective observational study including consecutive adult patients with idiopathic membranous nephropathy and NS. The diagnosis of NS was confirmed by the presence of a daily protein excretion greater than 3.5 g. Clinical and biological data, including coagulation and fibrinolytic system-related parameters, were obtained every 6 months during follow-up. Occurrence of VTE was the primary outcome of the study. Results: We enrolled 56 patients (52±11 years, 64% men). Median follow-up time was 12 [IQR: 12, 33] months. During follow-up 11 VTE occurred, 91 % of them in the first six months. Baseline proteinuria and serum albumin were associated with VTE (p<0.001). As for the haemostatic parameters, antithrombin III (ATIII) activity, protein C activity, plasminogen activator inhibitor-1 (PAI-1) and tisular plasminogen activator (tPA) levels were associated with an increased risk of VTE (all p<0.05), while protein S activity and fibrinogen were not. At multivariable analysis only ATIII activity (Exp(B) 0.86, 95% CI 0.75 to 0.98; p = 0.027) and serum albumin (Exp(B) 0.062, 95% CI 0.01 to 0.37; p = 0.002) remained independently associated with VTE. Conclusion: In this prospective study the risk of VTE was higher in the first 6 months of follow-up. Among the haemostasis-related parameters, only ATIII deficiency emerged as VTE independent risk factor in adult patients with idiopathic membranous nephropathy and NS.
1. Llach F: Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int. 1985; 28:429.
2. Singhal R, Brimble KS: Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res. 2006; 118:397.
3. Wei LQ, Rong ZK, Gui L, Shan RD: CT diagnosis of renal vein thrombosis in nephrotic syndrome. J Comput Assist Tomogr. 1991; 15:454.
4. Llach F, Papper S, Massry SG: The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med. 1980; 69:819.
5. Wagoner RD, Stanson AW, Holley KE, Winter CS: Renal vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome: incidence and significance. Kidney Int. 1983; 23:368.
6. Sarasin FP, Schifferli JA: Prophylactic oral anticoagulation in nephrotic patients with idiopathic membranous nephropathy. Kidney Int. 1994; 45:578.
7. Robert A, Olmer M, Sampol J, Gugliotta JE, Casanova P: Clinical correlation between hypercoagulability and thrombo-embolic phenomena. Kidney Int. 1987; 31:830 - 5.
8. Barbour SJ, Greenwald A, Djurdjev O, Levin A, Hladunewich NA, Nachman PH et al: Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012; 81:190.
9. Lionaki S, Derebail VK, Hogan SL, Barbour SJ, Lee T, Hladunewich NA et al: Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol. 2012; 7:43.
10. Levey AS, Greene T, Kusek JW, Beck GJ, MDRD Study Group: A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol., 2000, 11:A0828.
11. Andrassy K, Ritz E, Bommer J: Hypercoagulability in the nephrotic syndrome. Klin Wochenschr. 1980; 58:1029-36.
12. Cameron JS. The nephrotic syndrome and its complications. Am. J. Kidney Dis. 1987 Sep;10(3):157-71.
13. Di Nisio M, Squizzato A, Rutjes AW, Buller HR, Zwinderman AH, Bossuyt PM: Diagnostic accuracy of Ddimer test for exclusion of venous thromboembolism: A systematic review. J Thromb Haemost 2007; 5: 296 -304.
14. Mannucci PM, Valsecchi C, Bottasso B, D’Angelo A, Casati S, Ponticelli C: High plasma levels of protein C activity and antigen in the nephritic syndrome. Thromb Haemost 1986; 55(1): 31-33.
15. Haifeng Wu, Birmingham DJ, Rovin B, Hackshaw KV, Haddad N, Haden D et al: D-Dimer level and the risk for thrombosis in systemic lupus erythematosus.Clin J Am Soc Nephrol. 2008; 3: 1628-1636.
16. Mahmoodi BK, ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L et al: High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation 2008; 117:224.
17. Glassock RJ: Prophylactic Anticoagulation in Nephrotic Syndrome: A Clinical Conundrum. J Am Soc Nephrol. 2007;18: 2221-2225.
18. Kauffrnann RH, Veltkamp JJ, Van Tilburg NH, Van Es LA: Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med. 1978;65:607-13.
19. Boneu B, Bouissou F, Abbal M, Sie P, Caranobe C, Barthe P: Comparison of progressive antithrombin activity and the concentration of three thrombin inhibitors in nephrotic syndrome. Thromb Haemost. 1981;46:623-5.
20. Chemg SC, Huang WS, Wang YF, Yang SP, Lin YF: The role of lung scintigraphy in the diagnosis of nephrotic syndrome with pulmonary embolism. Clin Nucl Med 2000; 25:167- 72.
21. Citak A, Emre S, Sairin A, Bilge I, Nayir A: Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 2000;14:138- 42.
22. Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH: Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med 1994; 124(1):118-124.
23. Hamano K, Iwano M, Akai Y, Sato H, Kubo A, Nishitani Y et al: Expression of glomerular plasminogen activator inhibitor type 1 in glomerulonephritis. Am J Kidney Dis 2002; 39:695- 705.