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Acute Bilateral Renal Vein Thrombosis
IMAGING TEACHING CASE Acute Bilateral Renal Vein Thrombosis Qi Qian, MD,1,2 Nathan A. Saucier, MD,1 and Bernard F. King, MD3 INDEX WORDS: Renal vein thrombosis; renal vein obstruction; kidney biopsy; proteinuria; hematuria.
INTRODUCTION
R
enal vein thrombosis (RVT) in adults can occur in association with or as a consequence of severe nephrotic syndrome, renal cell carcinoma, trauma, infection, and a variety of systemic hypercoagulable states.1-4 Although chronic RVT may act as a source of embolus causing symptoms primarily related to recurrent pulmonary emboli, acute RVT typically presents with additional symptoms of flank pain, hematuria, and proteinuria.5 When bilateral and obstructing, acute RVT can cause sudden onset of gross hematuria, heavy proteinuria, and decreased kidney function. Systemic anticoagulation is the mainstay treatment of choice under such circumstances. Diagnostic kidney biopsy amidst propagating RVT carries a significant risk of postprocedural complications and may not add value to acute management. However, no clear practice guidelines exist for the acceptable timing of kidney biopsy in patients with acute RVT. This case illustrates the importance of the prompt recognition and management of bilateral obstructive RVT and the judicious timing of kidney biopsy to avoid unnecessary complications.
CASE REPORT Clinical History and Initial Laboratory Data A 61-year-old white man with a history of diabetes, hyperlipidemia, ulcerative colitis, obesity, and hypertension was admitted for acute onset of atraumatic gross hematuria, lower extremity swelling, loss of appetite, and dyspnea. His symptoms started a week prior when he noted a sudden onset of gross hematuria associated with lower back discomfort. Two days later, he developed bilateral lower extremity swelling and episodes of shortness of breath. In the succeeding days, his symptoms had become progressively worse with increasing frequency and duration of shortness of breath, which eventuated in the hospital admission. Despite having type 2 diabetes for ⬎20 years, the patient had no known history of albuminuria or serum creatinine level increase. His last routine physical examination was about a year before admission. He had been following a stable regimen of furosemide, glyburide, and atorvastatin for several years. His hypertension was not controlled opti-
mally, evidenced by several recorded systolic blood pressures ranging from 140-170 mm Hg. Initial evaluation showed mild lower extremity pitting edema, microscopic hematuria and heavy proteinuria on urine analysis (estimated urine protein excretion ⬎8 g/24 h), mild serum creatinine level increase of 1.2 mg/dL (106.1 mol/L; estimated glomerular filtration rate, 64 mL/min/ 1.73 m2 [1.07 mL/s/1.73 m2], calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation), and small bilateral pleural effusions on chest radiograph. Although the episodic shortness of breath may have resulted from embolic showers, a helical computed tomographic (CT) angiogram failed to show pulmonary embolism.
Imaging Studies Initial noncontrast images from a CT urogram showed no nephrolithiasis or abdominal masses. After intravenous contrast administration, there was a delay in the venous washout of the parenchyma and a delay in opacification of the collecting system of both kidneys. The delayed images showed bilateral RVT extending into the inferior vena cava. Figure 1A shows bilateral RVT with inferior vena cava extension on a reconstructed coronal image of the CT urogram. Kidney ultrasound showed an increase in echogenicity of the cortexes (Fig 2A). Doppler study of the renal arteries showed a reversed diastolic waveform; the antegrade flow in systole was followed by retrograde flow in diastole (Fig 2B) rather than a normal pattern of antegrade arterial flow throughout the cardiac cycle (Fig 2C). The retrograde flow, representing nonpropulsive rebound blood in the major renal arteries, indicates high resistance in the venous return, in this case, consistent with the presence of renal vein obstruction.6
Diagnosis Acute bilateral obstructive RVT.
From the 1Division of Nephrology and Hypertension and Departments of 2Physiology and Biomedical Engineering and 3Radiology, Mayo Clinic College of Medicine and Mayo Graduate School, Rochester, MN. Received February 19, 2009. Accepted in revised form June 8, 2009. Originally published online as doi: 10.1053/ j.ajkd.2009.06.035 on September 14, 2009. Address correspondence to Qi Qian, MD, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail: qian.qi@ mayo.edu © 2009 by the National Kidney Foundation, Inc. 0272-6386/09/5405-0024$36.00/0 doi:10.1053/j.ajkd.2009.06.035
American Journal of Kidney Diseases, Vol 54, No 5 (November), 2009: pp 975-978
975
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Qian, Saucier, and King
Figure 1. (A) Coronal reconstructed image from the patient’s computed tomographic (CT) urogram shows bilateral renal vein thrombosis (RVT) extending into the inferior vena cava with a delay in venous washout and opacification of the collecting system in both kidneys. (B) Repeated CT scan of the patient after 3 months of anticoagulation therapy shows resolution of RVT. A Gunther-Tulip filter is notable in the suprarenal inferior vena cava.
Clinical Follow-up After the discovery of RVT, intravenous heparin systemic anticoagulation therapy was initiated immediately. However, 10 hours later, this treatment was held because of the recurrence of gross hematuria. Given the high likelihood and ongoing risk of pulmonary embolism, an inferior vena cava filter was placed. Subsequent evaluations, including Doppler ultrasound of the lower extremities, cystoscopy, and bilateral ureteroscopy, showed no evidence of abnormality. Intravenous heparin therapy was then restarted. Given the patient’s heavy proteinuria, hematuria, and serum creatinine level increase, a nephrology consultation was requested for a diagnostic kidney biopsy. The case was reviewed by our nephrology consulting team. After careful appraisal of the patient’s overall status, a unified decision was made to defer the immediate kidney biopsy and continue with full-scale anticoagulation therapy. Three days after the initiation of intravenous heparin therapy, the gross hematuria resolved and lower extremity edema lessened. Repeated laboratory tests showed decreases in proteinuria (protein excretion, 1.4 g/24-h urine collection) and serum creatinine level (1.0 mg/dL [88.4 mol/L]; estimated glomerular filtration rate, 81 mL/min/1.73 m2 [1.35 mL/s/1.73 m2]). The patient was transitioned to warfarin therapy for anticoagulation as an outpatient. At the patient’s 3 month follow-up visit, a repeated abdominal CT scan was obtained, which showed complete resolution of RVT (Fig 1B). However, he was found to have protein excretion of 6.8 g/24-h urine collection. A kidney biopsy, safely carried out, showed membranous nephropathy. Underlying malignancy was ruled out, and he received treatment with cyclosporine and continued with oral warfarin for anticoagulation. One year after the RVT episode, proteinuria decreased to protein excretion of 1.0 g/24 h, and serum creatinine level slightly increased to 1.1 mg/dL (97.2 mol/L; estimated glomerular filtration rate, 72 mL/min/ 1.73 m2 [1.20 mL/s/1.73 m2]). Because the risk of long-term anticoagulation-associated complications outweighed the risk of thrombosis recurrence at that juncture, warfarin therapy
was discontinued, and the patient was scheduled for regular clinical follow-up.
DISCUSSION Acute bilateral RVT is a potentially lifethreatening condition. Prompt diagnosis and management and judicious time selection for kidney biopsy can optimize the patient’s final outcome. As typified in this case, flank pain/discomfort, hematuria, and proteinuria are the principle symptoms and signs of acute RVT. When the enlarging thrombus fills the renal veins bilaterally and becomes obstructive, these clinical manifestations can acutely degenerate into gross hematuria, heavy proteinuria, and varying degrees of acute kidney injury. Such acute manifestations are triggered by a combination of renal vein obstruction and the absence of available collateral tracks for venous return.6,7 The high-pressure kidney arterial inflow and obstructed venous outflow (by the RVT) render the kidneys acutely hyperemic and swollen (up to twice their original sizes in animal studies).7 This is apparent in the Doppler tracing of the renal artery. Normally, there is forward flow throughout the cardiac cycle (Fig 2C), but in RVT with obstruction, the increased venous pressure leads to reversal of flow (negative velocity) during diastole (Fig 2B). Although such a Doppler waveform may also be found in other clinical settings (ie, high-grade renal artery stenosis), in the context of acute RVT, it is a reliable sign of renal vein obstruction.
Acute Renal Vein Thrombosis
Figure 2. (A) Longitudinal ultrasound image of the patient’s right kidney (delineated by*) shows increased echogenicity in the cortex caused by renal vein thrombosis. (B) Transverse image of the left kidney (delineated by*). Note the Doppler gate (red arrow) was centered in the left renal artery with the Doppler waveform showing forward flow during systole (white arrows) and reverse flow during diastole (white arrow heads). (C) Arterial waveform of the right renal artery from a healthy individual shows a normal pattern of arterial peak systolic velocity (arrows) followed by a low-resistance diastolic velocity (arrowheads) with forward flow throughout systole and diastole.
977
The key to management under such circumstance is prompt institution of systemic anticoagulation therapy because untreated RVT carries an alarmingly high (⬎50%) mortality rate.8,9 Continual anticoagulation therapy remits thrombus enlargement, promotes thrombus organization and recannulization, and, in some cases, completely eliminates the thrombus.10,11 These effects are inseparably connected to the patient’s final outcome. In our patient, the CT scan and Doppler ultrasound of the renal vasculature confirmed the presence of bilateral obstructive RVT. At that juncture, the importance of immediate treatment (anticoagulation) surpassed the importance of discerning the underlying renal pathological state for several reasons: a kidney biopsy would require interruption of life-saving anticoagulation therapy,12 the kidney hyperemia renders a high risk of postbiopsy bleeding,9 and last, the biopsy would not yield more pathological information than what could be obtained after clot stabilization. Nephrotic syndrome caused by intrinsic kidney disease, especially membranous nephropathy, is associated with the development of RVT, possibly resulting from excessive urinary loss of anticoagulating proteins.13-15 Conversely, acute RVT with obstruction from nonrenal causes could result in acute-onset heavy proteinuria and decreased kidney function.5 In this patient, the limited history regarding the duration and severity of proteinuria did not permit us to discern with certainty the true cause of RVT. However, the dramatic decrease in proteinuria and improvement in kidney clearance speaks for RVT as the cause of nephrotic-range proteinuria. On the other hand, membranous nephropathy and heavy proteinuria subsequently (3 months later) were diagnosed. He possibly could have had an insidious onset of membranous nephropathy, which could have contributed to some degree to the genesis of the RVT. Clinically, during the acute phase of RVT, attention should dwell on systemic anticoagulation therapy to stabilize the clots, along with other supportive measures, including adequate control of blood pressure regardless of the underlying cause. In summary, our experience in this case convinces us to be vigilant and exercise caution for the diagnosis and management of acute obstructing RVT and avoid untimely kidney biopsy in such circumstance. By prudent time selection
978
Qian, Saucier, and King
and risk stratification, we can accomplish both the treatment of RVT and attainment of kidney biopsy with maximum safety.
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Llach F: Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 28(3):429-439, 1985 2. Shih KL, Yen HH, Su WW, Soon MS, Hsia CH, Lin YM: Fulminant Budd-Chiari syndrome caused by renal cell carcinoma with hepatic vein invasion: report of a case. Eur J Gastroenterol Hepatol 21(2):222-224, 2009 3. Asghar M, Ahmed K, Shah SS, Siddique MK, Dasgupta P, Khan MS: Renal vein thrombosis. Eur J Vasc Endovasc Surg 34(2):217-223, 2007 4. Wysokinski WE, Gosk-Bierska I, Greene EL, Grill D, Wiste H, McBane RD II: Clinical characteristics and longterm follow-up of patients with renal vein thrombosis. Am J Kidney Dis 51(2):224-232, 2008 5. Llach F, Papper S, Massry SG: The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 69(6):819-827, 1980 6. Kribs SW, Rankin RN: Doppler ultrasonography after renal transplantation: value of reversed diastolic flow in diagnosing renal vein obstruction. Can Assoc Radiol J 44(6): 434-438, 1993
7. Robinson G: Researches into the connection existing between an unnatural degree of compression of the blood contained in the renal vessels and the presence of certain abnormal matters in the urine. Med Chir Trans 26:51-79, 1843 8. Kowal J, Figur A, Hitzig WM: Renal vein thrombosis and the nephrotic syndrome with complete remission. J Mt Sinai Hosp N Y 30:47-58, 1963 9. Rosenmann E, Pollak VE, Pirani CL: Renal vein thrombosis in the adult: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 47(4):269335, 1968 10. Suto M, Aviles DH: Treatment of inferior vena cava and renal vein thrombosis with low-molecular-weight heparin in a child with idiopathic membranous nephropathy. Clin Pediatr (Phila) 43(3):851-853, 2004 11. Zigman A, Yazbeck S, Emil S, Nguyen L: Renal vein thrombosis: a 10-year review. J Pediatr Surg 35(11):15401542, 2000 12. Tan TK, Outkerk M, Van Beek EJR: Deep vein thrombosis and pulmonary embolism. In: Hallett JW Jr, Mills JL, Earshaw JJ, Reekers JA, eds. Vascular and Endovascular Surgery. Edinburgh, Scotland, Mosby, 2004:626633 13. Kanfer A, Kleinknecht D, Broyer M, Josso F: Coagulation studies in 45 cases of nephrotic syndrome without uremia. Thromb Diath Haemorrh 24(3):562-571, 1970 14. Thomson C, Forbes CD, Prentice CR, Kennedy AC: Changes in blood coagulation and fibrinolysis in the nephrotic syndrome. Q J Med 43(171):399-407, 1974 15. Singhal R, Brimble KS: Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 118(3):397-407, 2006
INTRODUCTION
R
enal vein thrombosis (RVT) in adults can occur in association with or as a consequence of severe nephrotic syndrome, renal cell carcinoma, trauma, infection, and a variety of systemic hypercoagulable states.1-4 Although chronic RVT may act as a source of embolus causing symptoms primarily related to recurrent pulmonary emboli, acute RVT typically presents with additional symptoms of flank pain, hematuria, and proteinuria.5 When bilateral and obstructing, acute RVT can cause sudden onset of gross hematuria, heavy proteinuria, and decreased kidney function. Systemic anticoagulation is the mainstay treatment of choice under such circumstances. Diagnostic kidney biopsy amidst propagating RVT carries a significant risk of postprocedural complications and may not add value to acute management. However, no clear practice guidelines exist for the acceptable timing of kidney biopsy in patients with acute RVT. This case illustrates the importance of the prompt recognition and management of bilateral obstructive RVT and the judicious timing of kidney biopsy to avoid unnecessary complications.
CASE REPORT Clinical History and Initial Laboratory Data A 61-year-old white man with a history of diabetes, hyperlipidemia, ulcerative colitis, obesity, and hypertension was admitted for acute onset of atraumatic gross hematuria, lower extremity swelling, loss of appetite, and dyspnea. His symptoms started a week prior when he noted a sudden onset of gross hematuria associated with lower back discomfort. Two days later, he developed bilateral lower extremity swelling and episodes of shortness of breath. In the succeeding days, his symptoms had become progressively worse with increasing frequency and duration of shortness of breath, which eventuated in the hospital admission. Despite having type 2 diabetes for ⬎20 years, the patient had no known history of albuminuria or serum creatinine level increase. His last routine physical examination was about a year before admission. He had been following a stable regimen of furosemide, glyburide, and atorvastatin for several years. His hypertension was not controlled opti-
mally, evidenced by several recorded systolic blood pressures ranging from 140-170 mm Hg. Initial evaluation showed mild lower extremity pitting edema, microscopic hematuria and heavy proteinuria on urine analysis (estimated urine protein excretion ⬎8 g/24 h), mild serum creatinine level increase of 1.2 mg/dL (106.1 mol/L; estimated glomerular filtration rate, 64 mL/min/ 1.73 m2 [1.07 mL/s/1.73 m2], calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation), and small bilateral pleural effusions on chest radiograph. Although the episodic shortness of breath may have resulted from embolic showers, a helical computed tomographic (CT) angiogram failed to show pulmonary embolism.
Imaging Studies Initial noncontrast images from a CT urogram showed no nephrolithiasis or abdominal masses. After intravenous contrast administration, there was a delay in the venous washout of the parenchyma and a delay in opacification of the collecting system of both kidneys. The delayed images showed bilateral RVT extending into the inferior vena cava. Figure 1A shows bilateral RVT with inferior vena cava extension on a reconstructed coronal image of the CT urogram. Kidney ultrasound showed an increase in echogenicity of the cortexes (Fig 2A). Doppler study of the renal arteries showed a reversed diastolic waveform; the antegrade flow in systole was followed by retrograde flow in diastole (Fig 2B) rather than a normal pattern of antegrade arterial flow throughout the cardiac cycle (Fig 2C). The retrograde flow, representing nonpropulsive rebound blood in the major renal arteries, indicates high resistance in the venous return, in this case, consistent with the presence of renal vein obstruction.6
Diagnosis Acute bilateral obstructive RVT.
From the 1Division of Nephrology and Hypertension and Departments of 2Physiology and Biomedical Engineering and 3Radiology, Mayo Clinic College of Medicine and Mayo Graduate School, Rochester, MN. Received February 19, 2009. Accepted in revised form June 8, 2009. Originally published online as doi: 10.1053/ j.ajkd.2009.06.035 on September 14, 2009. Address correspondence to Qi Qian, MD, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail: qian.qi@ mayo.edu © 2009 by the National Kidney Foundation, Inc. 0272-6386/09/5405-0024$36.00/0 doi:10.1053/j.ajkd.2009.06.035
American Journal of Kidney Diseases, Vol 54, No 5 (November), 2009: pp 975-978
975
976
Qian, Saucier, and King
Figure 1. (A) Coronal reconstructed image from the patient’s computed tomographic (CT) urogram shows bilateral renal vein thrombosis (RVT) extending into the inferior vena cava with a delay in venous washout and opacification of the collecting system in both kidneys. (B) Repeated CT scan of the patient after 3 months of anticoagulation therapy shows resolution of RVT. A Gunther-Tulip filter is notable in the suprarenal inferior vena cava.
Clinical Follow-up After the discovery of RVT, intravenous heparin systemic anticoagulation therapy was initiated immediately. However, 10 hours later, this treatment was held because of the recurrence of gross hematuria. Given the high likelihood and ongoing risk of pulmonary embolism, an inferior vena cava filter was placed. Subsequent evaluations, including Doppler ultrasound of the lower extremities, cystoscopy, and bilateral ureteroscopy, showed no evidence of abnormality. Intravenous heparin therapy was then restarted. Given the patient’s heavy proteinuria, hematuria, and serum creatinine level increase, a nephrology consultation was requested for a diagnostic kidney biopsy. The case was reviewed by our nephrology consulting team. After careful appraisal of the patient’s overall status, a unified decision was made to defer the immediate kidney biopsy and continue with full-scale anticoagulation therapy. Three days after the initiation of intravenous heparin therapy, the gross hematuria resolved and lower extremity edema lessened. Repeated laboratory tests showed decreases in proteinuria (protein excretion, 1.4 g/24-h urine collection) and serum creatinine level (1.0 mg/dL [88.4 mol/L]; estimated glomerular filtration rate, 81 mL/min/1.73 m2 [1.35 mL/s/1.73 m2]). The patient was transitioned to warfarin therapy for anticoagulation as an outpatient. At the patient’s 3 month follow-up visit, a repeated abdominal CT scan was obtained, which showed complete resolution of RVT (Fig 1B). However, he was found to have protein excretion of 6.8 g/24-h urine collection. A kidney biopsy, safely carried out, showed membranous nephropathy. Underlying malignancy was ruled out, and he received treatment with cyclosporine and continued with oral warfarin for anticoagulation. One year after the RVT episode, proteinuria decreased to protein excretion of 1.0 g/24 h, and serum creatinine level slightly increased to 1.1 mg/dL (97.2 mol/L; estimated glomerular filtration rate, 72 mL/min/ 1.73 m2 [1.20 mL/s/1.73 m2]). Because the risk of long-term anticoagulation-associated complications outweighed the risk of thrombosis recurrence at that juncture, warfarin therapy
was discontinued, and the patient was scheduled for regular clinical follow-up.
DISCUSSION Acute bilateral RVT is a potentially lifethreatening condition. Prompt diagnosis and management and judicious time selection for kidney biopsy can optimize the patient’s final outcome. As typified in this case, flank pain/discomfort, hematuria, and proteinuria are the principle symptoms and signs of acute RVT. When the enlarging thrombus fills the renal veins bilaterally and becomes obstructive, these clinical manifestations can acutely degenerate into gross hematuria, heavy proteinuria, and varying degrees of acute kidney injury. Such acute manifestations are triggered by a combination of renal vein obstruction and the absence of available collateral tracks for venous return.6,7 The high-pressure kidney arterial inflow and obstructed venous outflow (by the RVT) render the kidneys acutely hyperemic and swollen (up to twice their original sizes in animal studies).7 This is apparent in the Doppler tracing of the renal artery. Normally, there is forward flow throughout the cardiac cycle (Fig 2C), but in RVT with obstruction, the increased venous pressure leads to reversal of flow (negative velocity) during diastole (Fig 2B). Although such a Doppler waveform may also be found in other clinical settings (ie, high-grade renal artery stenosis), in the context of acute RVT, it is a reliable sign of renal vein obstruction.
Acute Renal Vein Thrombosis
Figure 2. (A) Longitudinal ultrasound image of the patient’s right kidney (delineated by*) shows increased echogenicity in the cortex caused by renal vein thrombosis. (B) Transverse image of the left kidney (delineated by*). Note the Doppler gate (red arrow) was centered in the left renal artery with the Doppler waveform showing forward flow during systole (white arrows) and reverse flow during diastole (white arrow heads). (C) Arterial waveform of the right renal artery from a healthy individual shows a normal pattern of arterial peak systolic velocity (arrows) followed by a low-resistance diastolic velocity (arrowheads) with forward flow throughout systole and diastole.
977
The key to management under such circumstance is prompt institution of systemic anticoagulation therapy because untreated RVT carries an alarmingly high (⬎50%) mortality rate.8,9 Continual anticoagulation therapy remits thrombus enlargement, promotes thrombus organization and recannulization, and, in some cases, completely eliminates the thrombus.10,11 These effects are inseparably connected to the patient’s final outcome. In our patient, the CT scan and Doppler ultrasound of the renal vasculature confirmed the presence of bilateral obstructive RVT. At that juncture, the importance of immediate treatment (anticoagulation) surpassed the importance of discerning the underlying renal pathological state for several reasons: a kidney biopsy would require interruption of life-saving anticoagulation therapy,12 the kidney hyperemia renders a high risk of postbiopsy bleeding,9 and last, the biopsy would not yield more pathological information than what could be obtained after clot stabilization. Nephrotic syndrome caused by intrinsic kidney disease, especially membranous nephropathy, is associated with the development of RVT, possibly resulting from excessive urinary loss of anticoagulating proteins.13-15 Conversely, acute RVT with obstruction from nonrenal causes could result in acute-onset heavy proteinuria and decreased kidney function.5 In this patient, the limited history regarding the duration and severity of proteinuria did not permit us to discern with certainty the true cause of RVT. However, the dramatic decrease in proteinuria and improvement in kidney clearance speaks for RVT as the cause of nephrotic-range proteinuria. On the other hand, membranous nephropathy and heavy proteinuria subsequently (3 months later) were diagnosed. He possibly could have had an insidious onset of membranous nephropathy, which could have contributed to some degree to the genesis of the RVT. Clinically, during the acute phase of RVT, attention should dwell on systemic anticoagulation therapy to stabilize the clots, along with other supportive measures, including adequate control of blood pressure regardless of the underlying cause. In summary, our experience in this case convinces us to be vigilant and exercise caution for the diagnosis and management of acute obstructing RVT and avoid untimely kidney biopsy in such circumstance. By prudent time selection
978
Qian, Saucier, and King
and risk stratification, we can accomplish both the treatment of RVT and attainment of kidney biopsy with maximum safety.
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Llach F: Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 28(3):429-439, 1985 2. Shih KL, Yen HH, Su WW, Soon MS, Hsia CH, Lin YM: Fulminant Budd-Chiari syndrome caused by renal cell carcinoma with hepatic vein invasion: report of a case. Eur J Gastroenterol Hepatol 21(2):222-224, 2009 3. Asghar M, Ahmed K, Shah SS, Siddique MK, Dasgupta P, Khan MS: Renal vein thrombosis. Eur J Vasc Endovasc Surg 34(2):217-223, 2007 4. Wysokinski WE, Gosk-Bierska I, Greene EL, Grill D, Wiste H, McBane RD II: Clinical characteristics and longterm follow-up of patients with renal vein thrombosis. Am J Kidney Dis 51(2):224-232, 2008 5. Llach F, Papper S, Massry SG: The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 69(6):819-827, 1980 6. Kribs SW, Rankin RN: Doppler ultrasonography after renal transplantation: value of reversed diastolic flow in diagnosing renal vein obstruction. Can Assoc Radiol J 44(6): 434-438, 1993
7. Robinson G: Researches into the connection existing between an unnatural degree of compression of the blood contained in the renal vessels and the presence of certain abnormal matters in the urine. Med Chir Trans 26:51-79, 1843 8. Kowal J, Figur A, Hitzig WM: Renal vein thrombosis and the nephrotic syndrome with complete remission. J Mt Sinai Hosp N Y 30:47-58, 1963 9. Rosenmann E, Pollak VE, Pirani CL: Renal vein thrombosis in the adult: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 47(4):269335, 1968 10. Suto M, Aviles DH: Treatment of inferior vena cava and renal vein thrombosis with low-molecular-weight heparin in a child with idiopathic membranous nephropathy. Clin Pediatr (Phila) 43(3):851-853, 2004 11. Zigman A, Yazbeck S, Emil S, Nguyen L: Renal vein thrombosis: a 10-year review. J Pediatr Surg 35(11):15401542, 2000 12. Tan TK, Outkerk M, Van Beek EJR: Deep vein thrombosis and pulmonary embolism. In: Hallett JW Jr, Mills JL, Earshaw JJ, Reekers JA, eds. Vascular and Endovascular Surgery. Edinburgh, Scotland, Mosby, 2004:626633 13. Kanfer A, Kleinknecht D, Broyer M, Josso F: Coagulation studies in 45 cases of nephrotic syndrome without uremia. Thromb Diath Haemorrh 24(3):562-571, 1970 14. Thomson C, Forbes CD, Prentice CR, Kennedy AC: Changes in blood coagulation and fibrinolysis in the nephrotic syndrome. Q J Med 43(171):399-407, 1974 15. Singhal R, Brimble KS: Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 118(3):397-407, 2006