Renal vein thrombosis and hypercoagulable state in nephrotic syndrome
- Jai Radhakrishnan, MD, MS
Jai Radhakrishnan, MD, MS
- Professor of Medicine
- Columbia University Medical Center
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
Patients with the nephrotic syndrome are at increased risk for venous thrombosis, particularly deep vein and renal vein thrombosis (DVT and RVT) [1-4]. Pulmonary embolization (mostly asymptomatic) is relatively common, and there are case reports of cerebral venous thrombosis [1-4]. Arterial thromboses (eg, limb and cerebral) also occur with higher frequency than in the general population [4-7].
This topic will review the epidemiology and pathogenesis of hypercoagulability in the nephrotic syndrome, and the clinical features and treatment of renal vein thrombosis in adults. Overviews of the nephrotic syndrome and causes of venous thrombosis are discussed separately. (See "Overview of heavy proteinuria and the nephrotic syndrome" and "Overview of the causes of venous thrombosis".)
The incidence of both venous and arterial thrombosis are much higher in patients with nephrotic syndrome compared with estimates in the general population. The magnitude of this effect was illustrated in a retrospective study of 298 (predominantly adult) patients who presented with the nephrotic syndrome and were followed for a mean of 10 years . The absolute risk of venous thrombosis was 1.0 percent per year, which is eight times higher than the age- and sex-matched annual incidence reported in the Worcester DVT study . The absolute risk of arterial thrombosis was 1.5 percent per year, also approximately eight times that observed in a general population . The risk of both venous and arterial thrombosis was greatest within the first six months of diagnosis (annual incidence 9.9 and 5.5 percent, respectively) .
An increase in thromboembolic risk is also present in children with the nephrotic syndrome. (See "Complications of nephrotic syndrome in children", section on 'Thromboembolism'.)
Risk factors — The risk of thrombosis varies among the causes of nephrotic syndrome and appears to be highest in patients with membranous nephropathy [4,10-13]. This was illustrated in a cohort of 1313 patients with idiopathic glomerular disease due to membranous nephropathy, focal segmental glomerulosclerosis, or IgA nephropathy . The incidence of venous thromboembolic events was much higher in membranous nephropathy (7.9 percent) and focal segmental glomerulosclerosis (3.0 percent) than in IgA nephropathy (0.4 percent). The histologic diagnosis remained a predictive factor for thrombosis after adjustment for the degree of proteinuria (which was much higher at presentation in membranous nephropathy and focal segmental glomerulosclerosis [median 5.6 and 3.7 g/day versus 1.6 g/day in IgA nephropathy]) and the serum albumin concentration. (See "Treatment of idiopathic membranous nephropathy", section on 'Anticoagulation'.)
- Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985; 28:429.
- Rabelink TJ, Zwaginga JJ, Koomans HA, Sixma JJ. Thrombosis and hemostasis in renal disease. Kidney Int 1994; 46:287.
- Crew RJ, Radhakrishnan J, Appel G. Complications of the nephrotic syndrome and their treatment. Clin Nephrol 2004; 62:245.
- Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 2006; 118:397.
- Tarry WC, Moser AJ, Makhoul RG. Peripheral arterial thrombosis in the nephrotic syndrome. Surgery 1993; 114:618.
- Parag KB, Somers SR, Seedat YK, et al. Arterial thrombosis in nephrotic syndrome. Am J Kidney Dis 1990; 15:176.
- 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.
- Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151:933.
- Thom TJ, Kannel WB, Silbershatz H, et al. Incidence, prevalence and mortality of cardiovascular diseases in the United States. In: Hurst's The Heart, 9th ed, Alexander RW, Schlant RC, Fuster V (Eds), McGraw-Hill, New York 1998. p.3.
- Barbour SJ, Greenwald A, Djurdjev O, et al. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int 2012; 81:190.
- Lionaki S, Derebail VK, Hogan SL, et al. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 2012; 7:43.
- Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980; 69:819.
- Chugh KS, Malik N, Uberoi HS, et al. Renal vein thrombosis in nephrotic syndrome--a prospective study and review. Postgrad Med J 1981; 57:566.
- Mercadal L, Montcel ST, Nochy D, et al. Factors affecting outcome and prognosis in membranous lupus nephropathy. Nephrol Dial Transplant 2002; 17:1771.
- Cherng SC, Huang WS, Wang YF, et al. The role of lung scintigraphy in the diagnosis of nephrotic syndrome with pulmonary embolism. Clin Nucl Med 2000; 25:167.
- Kuhlmann U, Steurer J, Bollinger A, et al. [Incidence and clinical significance of thromboses and thrombo-embolic complications in nephrotic syndrome patients]. Schweiz Med Wochenschr 1981; 111:1034.
- Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2007; 2:445.
- Wei LQ, Rong ZK, Gui L, Shan RD. CT diagnosis of renal vein thrombosis in nephrotic syndrome. J Comput Assist Tomogr 1991; 15:454.
- 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.
- Velasquez Forero F, Garcia Prugue N, Ruiz Morales N. Idiopathic nephrotic syndrome of the adult with asymptomatic thrombosis of the renal vein. Am J Nephrol 1988; 8:457.
- Liu YC, Wang HY, Pan JS. [Renal vein thrombosis in nephrotic syndrome--a prospective study of 54 cases]. Zhonghua Nei Ke Za Zhi 1989; 28:208.
- Kayali F, Najjar R, Aswad F, et al. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med 2008; 121:226.
- Andrassy K, Ritz E, Bommer J. Hypercoagulability in the Nephrotic syndrome. Klin Wochenschr 1980; 58:1029.
- Sarasin FP, Schifferli JA. Prophylactic oral anticoagulation in nephrotic patients with idiopathic membranous nephropathy. Kidney Int 1994; 45:578.
- Chen TY, Huang CC, Tsao CJ. Hemostatic molecular markers in nephrotic syndrome. Am J Hematol 1993; 44:276.
- Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med 2013; 368:956.
- Robert A, Olmer M, Sampol J, et al. Clinical correlation between hypercoagulability and thrombo-embolic phenomena. Kidney Int 1987; 31:830.
- Alkjaersig N, Fletcher AP, Narayanan M, Robson AM. Course and resolution of the coagulopathy in nephrotic children. Kidney Int 1987; 31:772.
- Wakui H, Imai H, Komatsuda A, Miura AB. Circulating antibodies against alpha-enolase in patients with primary membranous nephropathy (MN). Clin Exp Immunol 1999; 118:445.
- López-Alemany R, Longstaff C, Hawley S, et al. Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase. Am J Hematol 2003; 72:234.
- Zucchelli P. Renal vein thrombosis. Nephrol Dial Transplant 1992; 7 Suppl 1:105.
- Wysokinski WE, Gosk-Bierska I, Greene EL, et al. Clinical characteristics and long-term follow-up of patients with renal vein thrombosis. Am J Kidney Dis 2008; 51:224.
- Wolak T, Rogachev B, Tovbin D, et al. Renal vein thrombosis as a presenting symptom of multiple genetic pro-coagulant defects. Nephrol Dial Transplant 2005; 20:827.
- Kauffmann RH, de Graeff J, de la Rivière 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.
- Morrissey EC, McDonald BR, Rabetoy GM. Resolution of proteinuria secondary to bilateral renal vein thrombosis after treatment with systemic thrombolytic therapy. Am J Kidney Dis 1997; 29:615.
- Glassock RJ. Diagnosis and natural course of membranous nephropathy. Semin Nephrol 2003; 23:324.
- Rahmouni A, Jazaerli N, Radier C, et al. Evaluation of magnetic resonance imaging for the assessment of renal vein thrombosis in the nephrotic syndrome. Nephron 1994; 68:271.
- Tempany CM, Morton RA, Marshall FF. MRI of the renal veins: assessment of nonneoplastic venous thrombosis. J Comput Assist Tomogr 1992; 16:929.
- Avasthi PS, Greene ER, Scholler C, Fowler CR. Noninvasive diagnosis of renal vein thrombosis by ultrasonic echo-Doppler flowmetry. Kidney Int 1983; 23:882.
- Platt JF, Ellis JH, Rubin JM. Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney. AJR Am J Roentgenol 1994; 162:1367.
- Rostoker G, Durand-Zaleski I, Petit-Phar M, et al. Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin. Nephron 1995; 69:20.
- Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. J Am Soc Nephrol 2007; 18:2221.
- Lee T, Biddle AK, Lionaki S, et al. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. Kidney Int 2014; 85:1412.
- Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58:395.
- Medjeral-Thomas N, Ziaj S, Condon M, et al. Retrospective analysis of a novel regimen for the prevention of venous thromboembolism in nephrotic syndrome. Clin J Am Soc Nephrol 2014; 9:478.
- Sasaki Y, Raita Y, Uehara G, et al. Carotid thromboembolism associated with nephrotic syndrome treated with dabigatran. Case Rep Nephrol Urol 2014; 4:42.
- Dupree LH, Reddy P. Use of rivaroxaban in a patient with history of nephrotic syndrome and hypercoagulability. Ann Pharmacother 2014; 48:1655.
- Wu CH, Ko SF, Lee CH, et al. Successful outpatient treatment of renal vein thrombosis by low-molecular weight heparins in 3 patients with nephrotic syndrome. Clin Nephrol 2006; 65:433.
- Greenfield LJ, Cho KJ, Proctor MC, et al. Late results of suprarenal Greenfield vena cava filter placement. Arch Surg 1992; 127:969.
- Markowitz GS, Brignol F, Burns ER, et al. Renal vein thrombosis treated with thrombolytic therapy: case report and brief review. Am J Kidney Dis 1995; 25:801.
- Laville M, Aguilera D, Maillet PJ, et al. The prognosis of renal vein thrombosis: a re-evaluation of 27 cases. Nephrol Dial Transplant 1988; 3:247.
- Burrow CR, Walker WG, Bell WR, Gatewood OB. Streptokinase salvage of renal function after renal vein thrombosis. Ann Intern Med 1984; 100:237.
- Lam KK, Lui CC. Successful treatment of acute inferior vena cava and unilateral renal vein thrombosis by local infusion of recombinant tissue plasminogen activator. Am J Kidney Dis 1998; 32:1075.
- Kim HS, Fine DM, Atta MG. Catheter-directed thrombectomy and thrombolysis for acute renal vein thrombosis. J Vasc Interv Radiol 2006; 17:815.
- Weger N, Stawicki SP, Roll G, et al. Bilateral renal vein thrombosis secondary to membraneous glomerulonephritis: successful treatment with thrombolytic therapy. Ann Vasc Surg 2006; 20:411.
- Jaar BG, Kim HS, Samaniego MD, et al. Percutaneous mechanical thrombectomy: a new approach in the treatment of acute renal-vein thrombosis. Nephrol Dial Transplant 2002; 17:1122.
- Duffy JL, Letteri J, Clinque T, et al. Renal vein thrombosis and the nephrotic syndrome. Report of two cases with successful treatment of one. Am J Med 1973; 54:663.
- Risk factors
- Renal vein thrombosis
- Deep vein thrombosis
- Pulmonary embolism
- RENAL VEIN THROMBOSIS
- Clinical features
- - Chronic renal vein thrombosis
- - Acute renal vein thrombosis
- Diagnosis and screening
- Prevention of thromboembolism
- - Prophylactic anticoagulation
- Approach to prophylactic anticoagulation
- - Choice of anticoagulant
- - Anticoagulation for asymptomatic RVT
- - Anticoagulation for a thromboembolic event
- - Duration of anticoagulation
- - Inferior vena cava filters
- Direct therapy of RVT
- - Fibrinolytic therapy and catheter thrombectomy
- - Surgery
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS