Version May 2024
INTRODUCTION — Renal vein thrombosis (RVT) describes a condition in which thrombus forms in the renal veins or their branches. RVT is rare and occurs most commonly in adults with nephrotic syndrome and newborn infants with volume contraction or inherited thrombophilia. It may present acutely with associated symptoms (such as flank pain, hematuria, and/or acute kidney injury [AKI]) or may remain asymptomatic and undiagnosed until complicated by pulmonary embolism (PE) or discovered incidentally by imaging studies.
This topic will review the clinical features and treatment of RVT in adults. Overviews of the nephrotic syndrome and causes of venous thrombosis are discussed separately:
●(See "Overview of heavy proteinuria and the nephrotic syndrome".)
●(See "Overview of the causes of venous thrombosis".)
●(See "Hypercoagulability in nephrotic syndrome".)
EPIDEMIOLOGY — There is wide variability in the reported rate of RVT, probably related to the selection of patients for study (eg, degree of nephrotic syndrome, and symptomatic or asymptomatic thrombosis since RVT is often clinically silent or mistakenly attributed to another cause) and methods of detection (since the sensitivities of the available tests differ).
The prevalence of RVT in patients with the nephrotic syndrome ranges from 5 to over 60 percent [1-5]. In studies of consecutive or unselected patients without membranous nephropathy who underwent venography, the prevalence of RVT ranges from 10 to 50 percent, most frequently due to minimal change disease, membranoproliferative glomerulonephritis, and focal segmental glomerulosclerosis [4]. A higher prevalence has been noted in patients with membranous nephropathy (20 to 60 percent) [4,6-10]. In the largest available prospective series of 151 patients with nephrotic syndrome (mean serum albumin 2.1 to 2.4 g/dL [21 to 24 g/L] and protein excretion 5.0 to 5.8 g/day), RVT was detected in 33 patients overall (22 percent) and in 20 of 69 patients with membranous nephropathy (29 percent) [6]. (See "Hypercoagulability in nephrotic syndrome".)
Spontaneous RVT is rare in ambulatory individuals who are not nephrotic or without an underlying renal malignancy [11,12]. Among 218 patients who presented with RVT in a single-center study, 143 had a malignancy (111 with renal cell carcinoma) and 43 patients had the nephrotic syndrome [12]. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma".)
Some reported additional causes include trauma (including kidney biopsy), oral contraceptives, hypovolemia (especially in infants), inherited procoagulant defects, or extrarenal compression of the renal vein [11,13]. These patients did not become nephrotic, which demonstrates the important point that nephrotic syndrome is a cause, not the result, of RVT. RVT has also been reported in patients with coronavirus disease 2019 (COVID-19) [14]. (See "COVID-19: Hypercoagulability".)
CLINICAL FEATURES — RVT may be unilateral or bilateral and may extend into the inferior vena cava (IVC). Although RVT is more often chronic, acute RVT can occur and has a more dramatic presentation [15].
Acute RVT — Acute RVT is most often due to trauma, severe dehydration (especially in infants), or a generalized hypercoagulable state. It is an uncommon complication of the nephrotic syndrome [1]. (See "Overview of the causes of venous thrombosis" and "Hypercoagulability in nephrotic syndrome".)
Acute RVT typically presents with symptoms of renal infarction, including flank pain, microscopic or gross hematuria, a marked elevation in serum lactate dehydrogenase (without change in transaminases), and an increase in renal size on radiographic study [1]. Bilateral RVT can present with acute kidney injury (AKI).
Significant proteinuria is a rare complication of acute RVT in patients without underlying nephrotic syndrome [6,16]. In a case report, a previously healthy individual with bilateral RVT presented acutely with lower abdominal and flank pain and proteinuria (2.3 g over 24 hours); both the thrombus and proteinuria disappeared after two courses of urokinase following intravenous (IV) heparin [16]. The kidney appeared normal on subsequent kidney biopsy.
Chronic RVT — RVT most often has an insidious onset and produces no symptoms referable to the kidney [6,8,9]. In such patients, a pulmonary embolus is usually the only clinical clue to the possible presence of RVT or other deep vein thrombosis (DVT). Abnormal ventilation-perfusion scans (V/Q scans) of the lungs indicative or suggestive of pulmonary emboli have been found in as many as 10 to 30 percent of patients with chronic RVT, most of whom are asymptomatic [1,4,6-9,17,18]. (See "Hypercoagulability in nephrotic syndrome", section on 'Pulmonary embolism'.)
It has been suggested that a chronic RVT in patients with nephrotic syndrome may lead to increased proteinuria or progressively worsening kidney function. However, this has never been clearly documented [8]. Furthermore, 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 [19].
SURVEILLANCE — Routine surveillance for RVT is not recommended in patients with nephrotic syndrome, even in those at high risk for RVT (eg, membranous nephropathy associated with protein excretion above 10 g/day and/or a serum albumin concentration below 2 g/dL [20 g/L]) [2]. In addition, we do not screen nephrotic patients with worsening nephrotic syndrome or slowly rising serum creatinine. However, patients with nephrotic syndrome at high risk for thrombosis should be evaluated for possible prophylactic anticoagulation. (See "Hypercoagulability in nephrotic syndrome".)
Several considerations limit the value of routine surveillance for RVT in asymptomatic patients with nephrotic syndrome: The evaluation of RVT potentially exposes patients to radiation and intravenous contrast; a patient with a negative study may develop RVT at a later time, requiring sequential studies; and there are no data demonstrating a benefit to diagnosing occult disease [2]. However, the detection of occult disease should prompt a reevaluation of the risks and benefit of anticoagulation if the patient is not already receiving such therapy. (See "Hypercoagulability in nephrotic syndrome".)
It is also not particularly useful to evaluate for RVT in a patient who experiences an overt embolic event (such as a pulmonary embolus) for the following reasons:
●It cannot be proven that the pulmonary embolus originated in the renal veins, since a deep vein thrombosis (DVT) in the lower extremities may have coexisted.
●In situ pulmonary thrombosis (not an embolus) may occur in patients with severe nephrotic syndrome and profound hypoalbuminemia.
●Most important, a patient with nephrotic syndrome who has developed a thromboembolic event will be treated with anticoagulants whether or not an RVT is present.
Taking all of these factors into consideration, it is rarely necessary to image the renal veins for a thrombus in patients with the nephrotic syndrome. An important exception occurs in the rare patient suspected of having acute, complete RVT (eg, signs or symptoms of a renal infarct), which will be accompanied by acute kidney injury (AKI) if it is bilateral. (See 'Evaluation and diagnosis' below.)
A separate issue is whether chronic bilateral RVT might be a cause of a rising serum creatinine or increasing proteinuria and, if so, whether anticoagulation might be beneficial. There are no data to support this hypothesis [8]. Opinions of experts vary as to whether or not patients with marked and progressive nephrotic syndrome or a slowly rising serum creatinine should undergo an imaging procedure to screen for RVT.
EVALUATION AND DIAGNOSIS — As previously stated, most RVT is insidious and asymptomatic, and the diagnosis is established by imaging as an incidental finding. (See 'Chronic RVT' above.)
However, a diagnosis of acute, complete RVT should be suspected in patients with nephrotic syndrome who present with one of more of the following findings:
●New onset of flank pain or generalized abdominal pain
●New onset of gross hematuria
●New increase in serum creatinine that is otherwise unexplained
There are no specific laboratory tests to diagnose RVT. In patients who are suspected of having acute, complete RVT, imaging should be performed to confirm the diagnosis. Although the gold standard diagnostic test for RVT is selective renal venography (image 1), less invasive procedures are typically used, including computed tomography (CT) angiography and magnetic resonance (MR) venography [4,5,20-23].
Our approach to the selection of imaging modality is as follows:
●In patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, CT angiography is the preferred initial exam. The sensitivity and specificity of CT angiography for detecting RVT are approximately 92 and 100 percent, respectively, when compared with selective renal venography [5]. If CT angiography cannot be performed (eg, in patients who cannot receive iodinated intravenous [IV] contrast) or is unavailable, gadolinium-enhanced MR venography is the second-line option for initial imaging. When compared with CT angiography as a reference standard, the sensitivity and specificity of MR venography for RVT detection are approximately 94 and 100 percent, respectively [24].
●In patients with an eGFR <30 mL/min/1.73 m2 or with acute kidney injury (AKI), we avoid CT angiography since such patients may be at risk for contrast-induced nephropathy. We offer MR venography to the patient and discuss the potential risks and benefits of gadolinium contrast administration in patients with severe kidney function impairment. If the patient agrees to undergoing MR venography, group II gadolinium agents should be used, and group I agents should be avoided.
We do not routinely use Doppler ultrasonography to diagnose RVT in the native kidneys in view of the lower sensitivity with this technique. However, Doppler ultrasonography may be the only option if neither CT angiography nor MR venography is available. In one small study of 12 patients with suspected acute RVT, the absence or reversal of diastolic flow in the renal vein on Doppler ultrasonography had a sensitivity and specificity of only 40 and 47 percent, respectively, for detecting RVT when compared with renal venography or MR imaging (without gadolinium) [21]. There are no studies comparing the diagnostic accuracy of Doppler ultrasonography with that of CT angiography or MR venography. Although Doppler ultrasonography should not be used to evaluate for RVT in native kidneys, it is the exam of choice to detect RVT in the kidney allograft of kidney transplant recipients. (See "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction", section on 'Vascular thrombosis'.)
PREVENTION — Certain patients with the nephrotic syndrome may benefit from anticoagulation to prevent the development of thromboembolic events, including RVT. This issue is discussed in more detail elsewhere. (See "Hypercoagulability in nephrotic syndrome" and "Hypercoagulability in nephrotic syndrome", section on 'Prevention of thromboembolism'.)
TREATMENT
Patients with acute RVT — Management of an acute RVT depends upon whether the patient presents with acute kidney injury (AKI). In general, patients without AKI can be treated with therapeutic anticoagulation (unless contraindicated), whereas those with AKI should undergo dissolution or removal of the thrombus with thrombolytic therapy with or without thrombectomy.
Without acute kidney injury — Patients with an acute RVT or RVT with an associated thromboembolic event (deep vein thrombosis [DVT] or pulmonary embolism [PE]) who present without AKI are treated the same as patients who have a DVT or PE. Treatment typically consists of anticoagulation, unless contraindicated (table 1), initially with unfractionated or low-molecular-weight heparin and then warfarin [25,26]. Some patients with nephrotic syndrome are partially resistant to heparin therapy due to severe antithrombin deficiency.
●(See "Venous thromboembolism: Initiation of anticoagulation".)
●(See "Venous thromboembolism: Anticoagulation after initial management".)
Warfarin therapy is given for a minimum of 6 to 12 months. In patients with nephrotic syndrome, most experts feel that warfarin should be continued for as long as the patient remains nephrotic with a serum albumin concentration <3 g/dL [1,2].
The goal international normalized ratio (INR) is 2.0 to 3.0. This level of anticoagulation is associated with a modest increase in risk of bleeding; a higher bleeding risk, compared with less intense therapy, is observed particularly among older adults.
There is a paucity of data on the use of oral and parenteral direct thrombin inhibitors (eg, dabigatran, argatroban) and factor Xa inhibitors (eg, rivaroxaban, fondaparinux) in patients with nephrotic syndrome, and, in general, patients with impaired kidney function have been excluded from studies of these agents. In a retrospective study of 21 patients with nephrotic syndrome treated with direct oral anticoagulants (19 for thromboprophylaxis and 2 for thromboembolic events), none of the patients experienced thromboembolism and five patients experienced minor bleeding episodes [27]. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Settings in which a heparin or vitamin K antagonist may be preferable'.)
In patients who cannot receive therapeutic anticoagulation due to a contraindication, suprarenal inferior vena cava (IVC) filters have occasionally been used and are thought to be relatively safe [28]. It is unclear if patients with a documented RVT without PE and contraindications to anticoagulation should receive an IVC filter. (See "Placement of vena cava filters and their complications".)
With acute kidney injury — In patients with an acute RVT or RVT with an associated thromboembolic event (DVT or PE) who present with AKI, we favor local thrombolytic therapy with or without catheter thrombectomy. A combined approach is preferred for patients with bilateral RVT, a solitary kidney or transplanted kidney, or a large thrombus burden. Patients should then be maintained on therapeutic anticoagulation [15], as discussed above for patients with acute RVT who do not have AKI (see 'Without acute kidney injury' above). Systemic fibrinolysis has been used in patients with RVT but carries the risk of bleeding, including intracranial bleeding, and is not recommended [16,29-31]. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Complications'.)
Successful outcomes have been reported using local thrombolytic therapy with or without extraction catheter thrombectomy in nephrotic patients with acute RVT [32-35]. The potential efficacy of this approach was illustrated in a report of six patients (five of whom had proteinuric kidney disease, but level of proteinuria or serum albumin was not reported) with acute RVT who had percutaneous catheter thrombectomy followed by local thrombolysis for a mean of 22 hours [33]. Renal venous flow was restored in all patients, and the mean serum creatinine declined postprocedure from 3.3 to 1.9 mg/dL (292 to 168 micromol/L). At two years, kidney function was stable, and there were no further episodes of RVT.
Surgical thrombectomy is rarely performed given the availability of less invasive interventions such as catheter-directed thrombolysis and catheter thrombectomy. However, surgery is an alternative option for the rare patient with acute bilateral RVT and AKI who cannot be treated with percutaneous thrombectomy and/or thrombolysis [36].
Patients with chronic RVT — Chronic (asymptomatic) RVT is detected in one of two ways: during screening, which we do not recommend, and during imaging for some other reason. (See 'Chronic RVT' above and 'Surveillance' above.)
Therapeutic anticoagulation should be provided to patients with an incidentally discovered RVT, unless contraindicated. The approach to therapeutic anticoagulation in these patients is the same as that in patients with acute RVT or nonrenal thromboembolism. (See 'Without acute kidney injury' above.)
There are no randomized trials or definitive observational studies that have evaluated the role of anticoagulation in patients with nephrotic syndrome who have an asymptomatic RVT, but case series report treating such patients [6,8]. Possible benefits include prevention of extension of the RVT (eg, to the IVC), DVT, or PE, while the major risk is bleeding [6].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)
SUMMARY AND RECOMMENDATIONS
●Overview – Renal vein thrombosis (RVT) describes a condition in which thrombus forms in the renal veins or their branches. RVT is rare and occurs most commonly in adults with nephrotic syndrome and newborn infants with volume contraction or inherited thrombophilia. (See 'Introduction' above.)
●Epidemiology – The reported prevalence of RVT in patients with the nephrotic syndrome varies widely. Spontaneous RVT is rare in ambulatory individuals who are not nephrotic or without an underlying renal malignancy. Some reported additional causes of RVT include trauma (including kidney biopsy), oral contraceptives, hypovolemia (especially in infants), and inherited procoagulant disorders. (See 'Epidemiology' above.)
●Clinical features – Acute RVT typically presents with symptoms of renal infarction, including flank pain, microscopic or gross hematuria, a marked elevation in serum lactate dehydrogenase (without change in transaminases), and an increase in kidney size on radiographic study. Bilateral acute RVT can present with acute kidney injury (AKI). By contrast, chronic RVT most often has an insidious onset and produces no symptoms referable to the kidney. In such patients, a pulmonary embolus is usually the only clinical clue to the possible presence of RVT or other deep vein thrombosis (DVT). (See 'Clinical features' above.)
●Surveillance – Routine surveillance for RVT is not recommended in patients with nephrotic syndrome, even in those at high risk for RVT (eg, membranous nephropathy associated with protein excretion above 10 g/day and/or a serum albumin concentration below 2 g/dL [20 g/L]). In addition, we do not screen nephrotic patients with worsening nephrotic syndrome or slowly rising serum creatinine. (See 'Surveillance' above.)
●Evaluation and diagnosis – A diagnosis of acute, complete RVT should be suspected in patients with nephrotic syndrome who present with new onset of flank pain or generalized abdominal pain, new onset of gross hematuria, or new increase in serum creatinine that is otherwise unexplained. There are no specific laboratory tests to diagnose RVT. In patients who are suspected of having acute, complete RVT, imaging should be performed to confirm the diagnosis. Although the gold standard diagnostic test for RVT is selective renal venography, less invasive procedures are typically used, including computed tomography (CT) angiography and magnetic resonance (MR) venography. (See 'Evaluation and diagnosis' above.)
●Treatment
•Acute RVT – Management of an acute RVT depends upon whether the patient presents with AKI. In general, patients without AKI can be treated with therapeutic anticoagulation (unless contraindicated), whereas those with AKI should undergo dissolution or removal of the thrombus with thrombolytic therapy with or without thrombectomy.
-In patients with an acute RVT or RVT with an associated thromboembolic event (DVT or pulmonary embolism [PE]) who present without AKI, we recommend therapeutic anticoagulation rather than no anticoagulation (Grade 1B). Anticoagulation should be continued for as long as the patient remains nephrotic, for a minimum of 6 to 12 months. The goal international normalized ratio (INR) is 2 to 3. The role of direct oral anticoagulation in treating RVT has not been established. (See 'Without acute kidney injury' above.)
-In patients with an acute RVT or RVT with an associated thromboembolic event (DVT or PE) who present with AKI, we suggest local thrombolytic therapy with or without catheter thrombectomy (Grade 2C). Patients should then be maintained on therapeutic anticoagulation as is administered to patients with acute RVT who do not present with AKI. (See 'With acute kidney injury' above.)
•Chronic RVT – In patients with an incidentally discovered RVT, we suggest therapeutic anticoagulation rather than no anticoagulation (Grade 2C). The approach to therapeutic anticoagulation in these patients is the same as that in patients with acute RVT or nonrenal thromboembolism. (See 'Patients with chronic RVT' above.)
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