Renal vein thrombosis (RVT) most commonly occurs in patients with nephrotic syndrome (defined as urinary protein loss >3 g/day, hypoalbuminemia, hypercholesterolemia, and edema) due to the loss of antithrombin III (ATIII) in the urine, which in turn leads to an increase in hypercoagulability.[1] Other common causes of RVT include malignancies (eg, renal cell carcinoma [RCC]), instrumentation to the area, and any hypercoagulable state. These hypercoagulable states can be transient (eg, from pregnancy, oral contraceptives, or traumatic injury) or chronic (eg, from factor V Leiden, systemic lupus erythematosus [SLE], or deficiency of protein C or S).[2]
Treatment of RVT depends on the severity of symptoms but is typically managed with therapeutic anticoagulation to prevent potential thromboembolic complications. Intravenous (IV) unfractionated heparin (UFH) is often the first-line agent in the acute hospital setting, before transition to warfarin or a novel oral anticoagulant (NOAC) such as rivaroxaban or apixaban.[3, 4] In severe cases (eg, bilateral RVT with impending renal failure), thrombolysis or mechanical thrombectomy can be performed. In the most severe cases, in which RVT has caused capsular rupture of the kidney, urgent nephrectomy is performed to stop life-threatening hemorrhage.
In general, the fundamental principles of thrombosis apply to RVT, and any pathologic condition contributing to an aspect of the Virchow triad (endothelial disruption, stasis, hypercoagulability) will increase the risk that RVT will develop.[5] The left renal vein is three times more likely to be involved than the right renal vein, probably because of its greater length.
The most common etiology of RVT is the hypercoagulability resulting from nephrotic syndrome, with membranous nephropathy being the most common pathology. Membranous nephropathy is idiopathic in most cases, but it can also be caused by membranoproliferative glomerulonephritis, minimal change disease, rapidly progressive glomerulonephritis, amyloid, focal sclerosis, or lupus nephritis. RVT tends to be more common in patients with a primary nephropathy than in those with a secondary nephropathy.
Initially, nephrotic syndrome was believed to be a consequence of RVT; however, the following observations showed that this belief was mistaken:
In nephrotic syndrome, lower-molecular-weight proteins such as ATIII are lost in the urine, and this leads to hypercoagulability. Additionally, low oncotic pressure gradients may lead to hemoconcentration, which can further contribute to hypercoagulability. Other specific aspects of the underlying nephropathy not listed above may also cause systemic hypercoagulability.
Tumors (most commonly RCC) have a tendency to invade the renal vein and cause RVT. If the tumor is large, it can extend into the inferior vena cava (IVC). Extrinsic compression from mass effect may also cause a prothrombotic environment, even without direct invasion of the vein.
Other systemic diseases or processes associated with RVT include but are not limited to the following:
In cases of hypercoagulability resulting from systemic causes, thrombosis typically begins in the arcuate and intralobular venules and propagates outward. In cases resulting from extrinsic compression or instrumentation, thrombosis typically begins in the main renal vein or its primary tributaries.
The prevalence of RVT in the United States has been difficult to establish. Studies have shown a high degree of variability in the presence of RVT among patients with nephrotic syndrome, with reported rates ranging from 5% to 62%. Other studies have shown that RVT may develop in as many as 20% of patients with nephrotic syndrome, though it is often subclinical.
Age is a factor in RVT. For example, membranous nephropathy, which is most commonly associated with RVT, is also the most common cause of nephrotic syndrome in adults. RVT peaks in the fourth through sixth decades of life and rarely affects children. In infants, more than 80% of cases of RVT are diagnosed within the first month of life, typically resulting from severe dehydration, prolonged hypotension, inherited coagulable states, or some combination thereof. RVT from RCC typically affects older age groups but can also occur at any age with a history of malignancy, surgical instrumentation, or extrinsic compression.
No sex-specific data are available for the frequency of RVT. Theoretically, however, membranous nephropathy has a male-to-female ratio of 2:1; therefore, a male preponderance may exist for RVT.
Currently, there is little evidence to suggest that RVT has any a predilection for certain races or ethnicities.
The prognosis of patients with RVT is predicated on several factors, including the following:
Unilateral RVT will have a better prognosis than bilateral RVT. Sufficient collateralization and recanalization can slow and prevent the development of renal dysfunction.
Usually, however, morbidity and mortality are secondary to the effects of the underlying condition causing RVT (eg, nephrotic syndrome, malignancy,[9] trauma, or a hypercoagulable disorder). The prognosis of any glomerular disease may be worsened by the superimposition of an acute RVT, but it is unclear whether the slow development of chronic RVT accelerates renal functional loss.
In RVT secondary to malignant etiology, morbidity and mortality result from either thromboembolism or the cancer itself and may act as a signal of dissemination of the malignancy. In the setting of transplantation, RVT may lead to loss of the graft. When morbidity and mortality are directly caused by sequelae of RVT, they are typically due to thromboembolism resulting in caval thrombosis and pulmonary embolism (PE) or to renal dysfunction or failure. In severe cases where RVT causes capsular distention and rupture, morbidity is secondary to life-threatening retroperitoneal hemorrhage.
The presentation of renal vein thrombosis (RVT) is variable. Patients are often asymptomatic, with symptoms related only to the primary disease process, which may contribute to an RVT that is discovered incidentally on further workup.
If the condition is acute and giving rise to symptoms, patients may exhibit general malaise, abdominal distention, flank pain, hematuria, proteinuria, or hypertension. If the condition is severe, a thromboembolic complication with pulmonary embolism (PE) may be the initial presenting symptom. In rare severe cases (often bilateral), acute kidney injury (AKI; or acute renal failure [ARF]) or hemorrhage may be encountered.
In chronic cases, patients may remain asymptomatic and suddenly present with thromboembolism, a slow decline in renal function, or worsening proteinuria.
Potential complications of RVT include the following:
No specific laboratory studies are indicated for renal vein thrombosis (RVT) except those specific for nephrotic syndrome or other associated factors (eg, trauma or a coexisting hypercoagulable state[11] ). Studies that may be helpful include the following:
Computed tomography (CT) with intravenous (IV) contrast is regarded as the imaging modality of choice for diagnosing RVT, having nearly 100% sensitivity and specificity.[12] It tends to be the study most often ordered, given the typical presenting symptoms. The CT scan will directly show the thrombus and possible caval extension but can indirectly show kidney enlargement and perirenal densities indicative of dilated collaterals; it can also simultaneously provide information on potential causes of RVT. It must be kept in mind, however, that the IV contrast used in the procedure may be nephrotoxic and lead to worsening renal function.
Renal ultrasonography (US) is safe and noninvasive and remains an accurate and highly sensitive method of diagnosing RVT. Defining characteristics of RVT on US include renal enlargement without hydronephrosis, renal vein dilation, or visualized thrombus. Color Doppler may also show low or no flow or an obstructive signal. Renal US also allows the clinician to visualize the thrombus and determine its acuity on the basis of its echogenicity. Ultrasonograms are low-cost and easy to acquire; however, quality may vary, depending on the performing technician and on patient-specific factors (eg, body mass index [BMI] or bowel gas).
![]() View Image | CT scan shows renal vein thrombosis secondary to renal cell cancer. Arrow is pointed at thrombosed renal vein. |
Magnetic resonance imaging (MRI) is capable of imaging and diagnosing RVT with high definition and of differentiating soft-tissue structures with high accuracy (see the image below); however, it is expensive and time-consuming and often involves the use of gadolinium-based contrast agents that could cause nephrogenic systemic sclerosis in patients with a very low glomerular filtration rate (GFR).
![]() View Image | MRI is from patient with renal cell cancer and renal vein thrombosis. Arrow is on thrombosed renal vein. |
In RVT, intravenous pyelography (IVP) with an abdominal plain film may reveal an enlarged kidney. If the renal pelvis is observed, it is usually distorted. An infrequent but characteristic finding of RVT is “notching” of the ureter, which occurs when collateral veins near the ureters become tortuous. IVP is seldom used to aid in the diagnosis.
Inferior vena cavography may help provide a diagnosis of RVT. Occasionally, it is nondiagnostic, in which case selective renal vein catheterization can be performed. Renal arteriography may be useful in situations where RVT is secondary to trauma or tumor, in which case renal artery involvement is common. In general, any selective catheter-based imaging technique for diagnosis is reserved for situations where an intervention is planned.
With any of the aforementioned imaging techniques, significant venous collaterals will indicate a more chronic process.
Renal biopsy plays an essential role in the evaluation of patients who are nephrotic and who have RVT. Renal histologic features of these patients reflect the primary renal disease responsible. Membranous nephropathy is the most common finding (see the image below).
![]() View Image | Renal biopsy shows membranous nephropathy. Light (hematoxylin and eosin) stain shows thickened capillary loops via electron microscopy, with subepithe.... |
Treatment of renal vein thrombosis (RVT) is typically aimed at preventing further thromboembolism, as well as preserving renal function.[13] This is accomplished by initiating anticoagulation with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), followed by a transition to a vitamin K antagonist (VKA) such as warfarin. Some studies have demonstrated the efficacy of switching to a novel oral anticoagulant (NOAC) such as rivaroxaban[14] or apixaban.
Therapy is typically continued for 3-6 months in conjunction with treatment of the underlying cause. Anticoagulation should be prescribed for as long as the underlying cause is not treated. If the thrombosis is idiopathic or due to an irreversible cause, lifelong anticoagulation may be indicated.
Treatment of the underlying disease process remains a critical aspect of management. For example, symptomatic treatment includes diuretics and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) to reduce proteinuria from nephrotic syndrome; urinary protein is injurious to the renal tubules. Reduction of protein loss in the urine also decreases hypercoagulability. ACEIs and ARBs reduce urine protein by exerting an effect on efferent arteriolar pressure and are titrated to as high a dose as the patient can tolerate. If a combination of ACEIs and ARBs lowers protein excretion more than either does alone, then the two medications should be used together.
Atorvastatin may also be a useful adjuvant therapy. Bianchi et al suggested that atorvastatin could decrease the rate of progression of kidney disease, proteinuria, and hypercholesterolemia.[15]
Cyclosporine has also demonstrated benefit in early trials for treatment of membranous nephropathy. Cure of the underlying nephropathy reverses nephrotic syndrome and RVT.
Indications for systemic thrombolysis in the setting of RVT are unclear. No data are available comparing thrombolytic therapy with anticoagulation in this setting.[16] In pulmonary embolism (PE) from other causes, thrombolytics are indicated in the setting of pulmonary hypertension (diagnosed on examination or by echocardiography). Catheter-based techniques for rapid delivery of thrombolytics in the setting of acute or refractory RVT have also been described.[17, 18, 19, 20]
Surgical treatment of RVT is rare. When it is carried out, it is more commonly in the form of endovascular techniques performed by vascular surgeons or interventional radiologists. If there is a contraindication to anticoagulation, an inferior vena cava (IVC) filter can be placed to prevent PE; however, this would require suprarenal filter placement, which could cause morbid consequences if it were to thrombose.[21]
Other endovascular techniques include catheter-directed thrombolysis and thrombectomy, which are reserved for patients with bilateral RVT, acutely declining renal function, or caval involvement. The procedure typically involves obtaining percutaneous access to the venous system and deploying a series of wires and catheters in the IVC and the renal vein. Contrast-enhanced imaging directly diagnoses the thrombus and defines its extent, after which thrombolytics can be administered or mechanical/suction thrombectomy performed.
Some studies have described percutaneous access to the arterial system, whereby tissue plasminogen activator (t-PA) is locally administered into the renal artery to aid in restoring patency of the arcuate and intralobar vessels.
Open surgical management is rarely indicated and tends to be reserved for cases involving tumor resection, where a partial or total nephrectomy is performed. Prompt open nephrectomy is also indicated in extremely rare circumstances in which RVT has caused capsular rupture and life-threatening hemorrhage is present.
Many nephrologists recommend normal protein intake for patients with nephrotic syndrome. Protein restriction may benefit patients who do not excrete massive amounts of protein (~10 g or more over 24 hr) or in those who have chronic renal failure.[22]
Activity is allowed as tolerated.
Consultation with a nephrologist and a hematologist is likely to be immediately necessary, depending on the presentation. If surgical intervention is required, consultation with a urologist, a vascular surgeon, an interventional radiologist, a cardiac surgeon (for severe PE), or a transplant surgeon may be indicated, depending on the specific circumstances.
Reduction in proteinuria is essential in the treatment of renal vein thrombosis (RVT) in patients who are nephrotic. The current standard is to use angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs). Pulmonary emboli from RVT should be diagnosed and treated exactly as they are when resulting from other sources (ie, heparin, warfarin). If RVT is associated with pulmonary emboli, anticoagulation must be continued as long as nephrotic syndrome is present.
The indicators for thrombolysis in the setting of RVT are unclear. No data are available comparing thrombolytic therapy with anticoagulation. In pulmonary embolic disease from other causes, thrombolytics are indicated in the setting of pulmonary hypertension (diangosed on examination or 6by echocardiography).
Warfarin, ARBs, and ACEIs are unsafe in pregnancy. Pregnant patients with RVT are best treated with heparin alone.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
Clinical Context: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This increases levels of plasma renin and reduces aldosterone secretion. In kidney, the drug decreases glomerular hydraulic pressure, thereby decreasing filtration of protein.
These agents reduce urine protein excretion by decreasing glomerular hydraulic pressure. Decrease efferent arteriolar constriction, thereby decreasing the pressure, resulting in the filtration of protein. The filtered protein, per se, is injurious to the kidney.
Clinical Context: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACEIs.
Clinical Context: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACEIs.
Clinical Context: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACEIs.
Clinical Context: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACEIs.
Clinical Context: Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACEIs.
Clinical Context: Prodrug that produces direct antagonism of angiotensin II receptors. Displaces angiotensin II from AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. May induce more complete inhibition of renin-angiotensin system than ACEIs, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. For use in patients unable to tolerate ACEIs.
These agents reduce urine protein excretion by decreasing glomerular hydrostatic pressure.
Clinical Context: Intravenously (therapeutic dose) or subcutaneously (prophylactic dose) administered medication that is unfractionated and binds to several proteins (including antithrombin) in order to activate thrombin, a clotting factor. This ultimately blocks the clotting cascade, preventing clot formation and prolonging blood clotting time. Heparin dosing is variable among patients and must be monitored with activated partial thromboplastin time (aPTT) blood test.
Clinical Context: Low-molecular-weight heparin that is usually subcutaneously administered. It binds and potentiates antithrombin III indirectly to inhibit the coagulation cascade. Unlike heparin, enoxaparin has better activity against factor Xa and less inhibition towards thrombin; thus there is a decreased chance of heparin-induced thrombocytopenia. Enoxaparin also has better bioavailability than heparin and thus is dosed on the basis of weight without the need for level monitoring.
Clinical Context: Oral anticoagulant that inhibits vitamin K epoxide reductase complex 1, which decreases functional vitamin K and ultimately reduces synthesis of clotting factors. Dose response of warfarin is variable and depends on several patient factors, including diet, genetics, concurrent disease states, and drug interactions. Therefore, dosing of warfarin must be monitored via international normalized ratio (INR) levels.
Clinical Context: Novel oral anticoagulant that directly and reversibly binds to factor Xa to inhibit it, thereby also impeding the coagulation cascade. Metabolism of the medication occurs in the liver and thus is contraindicated in patients with liver failure. Monitoring of medication dosing is not needed.
Clinical Context: Novel oral anticoagulant that directly inhibits factor Xa, thereby eventually impeding the coagulation cascade. Apixaban can affect both free and clot-bound factor Xa. Monitoring of medication dosing is not needed.