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Patients with the nephrotic syndrome are at increased risk of developing venous and arterial thromboembolism, particularly RVT The mechanism of thromboembolism in nephrotic syndrome and optimal diagnostic and anticoagulant management strategies remain controversial
Study
Llach, et al. Am J Med 1980 Chugh, et al. Postgrad Med J 1981 Velasquez, et al. Am J Nephrol 1988 Wagoner, et al. Kidney Int 1983 Bennett, et al. Ann Intern Med 1975
Membranous GN
MPGN
MCD
FSGS
Other
Overall
29.0 (69)
22.2 (27)
20.0 (10)
25.0 (4)
9.8 (41)
21.9 (151)
42.9 (7)
20.0 (5)
26.3 (19)
0 (5)
25.0 (8)
25.0 (44)
60.0 (5)
40.0 (10)
0 (0)
28.6 (7)
50.0 (4)
42.3 (26)
51.9 (27)
0 (0)
0 (0)
0 (0)
0 (0)
51.9 (27)
28.6 (21)
Overall
37.0 (108)
26.2 (42)
24.1 (29)
18.8 (16)
15.1 (53)
27.9 (269)
A retrospective study involving 298 patients with mean follow up of 10 years showed annual incidences of VTE and ATE of 1.02% and 1.48% respectively Risks of both VTE and ATE were particularly high within the first 6 months of NS (annual incidences 9.85% and 5.52% respectively)
Mahmoodi et. Al Circulation. 2008 Jan 15;117(2):224-30
Clinical features
RVT may be unilateral or bilateral and may extend into the inferior vena cava
RVT most often has an insidious onset and produces no symptoms referable to the kidney
Acute RVT is usually due to trauma, severe dehydration or a generalized hypercoagulable state It typically presents with symptoms of renal infarction, including flank pain, microscopic or gross hematuria, a marked elevation in serum lactate dehydrogenase, and an increase in renal size on radiographic study Bilateral RVT may present with acute renal failure
Pathogenesis
Factor VIII levels are typically increased as much as 2- to 3-fold compared to controls and increased factor VIII may be a risk factor for venous thromboembolism There is an inverse correlation between serum albumin and fibrinogen levels in nephrotic syndrome Hyperfibrinogenemia may contribute to the procoagulant state by providing more substrate for fibrin formation and by promoting platelet hyperaggregability, increased blood viscosity, and red blood cell aggregation
Screening
Routine screening for RVT is not recommended in patients with nephrotic syndrome No proven benefit to diagnosing occult disease A patient with a negative study may develop RVT at a later time
It is also not useful to evaluate for RVT in a patient who experiences an overt embolic event such as PE It cannot be proven that the pulmonary embolus originated in the renal veins In situ pulmonary thrombosis may occur Patients will be treated with anticoagulants whether or not RVT is present
Diagnosis
Estimated sensitivity and specificity of CT with contrast was 92.3% and 100%, respectively Only a small number of studies have evaluated the value of MRI with or without contrast enhancement in the identification of RVT Only one study has prospectively evaluated Doppler ultrasonography in the diagnosis of RVT and found it to be 85% sensitive and 56% specific Intravenous pyelography was found to have a sensitivity of 34.1% and a specificity of 87.2% Selective renal venography is the reference standard diagnostic test for RVT
Treatment
The risks associated with asymptomatic RVT have not been compared to the risks of long term anticoagulation therefore prophylactic anticoagulation is not recommended There are no definitive studies that have evaluated the role of anticoagulation in patients with an asymptomatic RVT, but case series report treating such patients
Patients with a symptomatic RVT or a thromboembolic event in the absence of RVT are treated with low molecular weight heparin and then warfarin Some patients are partially resistant to heparin therapy due to severe antithrombin deficiency Warfarin therapy is given for a minimum of 6 to 12 months and some people recommend continuing treatment for as long as the patient remains nephrotic Local thrombolytic therapy with or without thrombectomy in patients who have signs of acute RVT has been successfully performed in small numbers of patients
Animal studies in which main renal vein occlusion was produced experimentally, have failed to demonstrate the development of heavy proteinuria unless the contralateral normal kidney is removed RVT in the absence of nephrotic syndrome has been reported in the literature Nephrotic patients with RVT who have undergone histologic evaluation show evidence of an identifiable glomerulopathy
In a case report of a patient with unilateral RVT and nephrotic syndrome due to membranous nephropathy, bilateral ureteral catheterization studies showed no difference in protein excretion or creatinine clearance between the two kidneys In retrospective studies, the sequence of nephrotic syndrome leading to renal vein thrombosis was clearly established However bilateral RVT has been reported to cause nephrotic syndrome
References
Radhakrishnan, J. Renal vein thrombosis and hypercoagulable state in nephrotic syndrome. Uptodat May 2009 Singhal, R, Brimble, KS. Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Thromb Res 2006; 118:397 F. Llach, S. Papper and S.G. Massry, The clinical spectrum of renal vein thrombosis: acute and chronic, Am J Med 69 (1980), pp. 819827 K.S. Chugh, N. Malik, H.S. Uberoi, V.K. Gupta, M.L. Aggarwal and P.C. Singhal et al., Renal vein thrombosis in nephrotic syndromea prospective study and review, Postgrad Med J. 57 (1981), pp. 566570 F.F. Velasquez, P.N. Garcia and M.N. Ruiz, Idiopathic nephrotic syndrome of the adult with asymptomatic thrombosis of the renal vein, Am J Nephrol 8 (1988), pp. 457462 R.D. Wagoner, A.W. Stanson, K.E. Holley and C.S. Winter, Renal vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome: incidence and significance, Kidney Int 23 (1983), pp. 368 374 W.M. Bennett, Renal vein thrombosis in nephrotic syndrome, Ann Intern Med 83 (1975), pp. 577578
References
Mahmoodi, BK, ten Kate, MK, Waanders, F, 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 R.H. Kauffrnann, J.J. Veltkamp, N.H. Van Tilburg and L.A. Van Es, Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome, Am J Med 65 (1978), pp. 607613 A. Citak, S. Emre, A. Sairin, I. Bilge and A. Nayir, Hemostatic problems and thromboembolic complications in nephrotic children, Pediatr Nephrol 14 (2000), pp. 138142 Fisher Er, Sharkey D, Pardo V, Vuzevski V. Experimental renal vein constriction: Its relation to renal lesions observed in human renal vein thrombosis and the nephrotic syndrome. Lab Invest 1968, 18:689-699 Wagoner, RD, Stanton, AW, Holley, KE, Winter, CS. Renal vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome: Incidence and significance. Kidney Int 1983; 23:368 Kauffmann, RH, de Graeff, J, de la, Riviere GB, van Es, LA. Unilateral renal vein thrombosis and nephrotic syndrome. Report of a case with protein selectivity and antithrombin III clearance studies. Am J Med 1976; 60:1048