AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Although renal vein thrombosis (RVT) has numerous etiologies, it occurs most commonly in patients with nephrotic syndrome (ie, > 3 g/d protein loss in the urine, hypoalbuminemia, hypercholesterolemia, edema).

The syndrome is responsible for a hypercoagulable state. The excessive urinary protein loss is associated with decreased antithrombin III, a relative excess of fibrinogen, and changes in other clotting factors; all lead to a propensity to clot. Numerous studies have demonstrated a direct relationship between nephrotic syndrome and both arterial and venous thromboses. Why the renal vein is susceptible to thrombosis is unclear.

The renal vein also may contain thrombus after invasion by renal cell cancer. Other less common causes include renal transplantation, Behçet syndrome, hypercoagulable states, and antiphospholipid antibody syndrome.

Pathophysiology

Hypercoagulability is the etiology for both arterial and venous thromboses. In the setting of malignant invasion of the vein by cancer, the presence of the tumor cells elicits thrombosis of the renal vein only.

Frequency

United States

Prevalence of RVT 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 of 5-62%.

Mortality/Morbidity

• The morbidity and mortality of RVT usually is secondary to the effects of nephrotic syndrome (including arterial thrombosis), renal dysfunction and/or failure, or the complications resulting from thromboembolism. If the etiology of the RVT is malignancy, morbidity and mortality are a result of either thromboembolism or the cancer itself. In the setting of transplantation, RVT may lead to loss of the graft. If the RVT eventuates from the other causes discussed, thromboembolism is the source of complications.

Race

• No race predilection exists.

Sex

• No specific numbers are available. However, theoretically, membranous nephropathy, the most commonly associated disease for RVT, has a male-to-female ratio of 2:1. Therefore, a male preponderance may exist.

Age

• Age is a factor in RVT only as associated with any age-related risk of glomerular disease. For example, membranous nephropathy, the lesion most associated with RVT, is the most common cause of nephrotic syndrome in adults, but it is rare in children. Membranous nephropathy peaks in the fourth through sixth decade, thus making RVT more likely in this specific age group. However, exact incidence or prevalence is not available.
• RVT from renal cell carcinoma occurs in older age groups.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The presentation of RVT is variable, and patients may be asymptomatic. When RVT occurs as a result of malignancy, the signs of the renal malignancy (eg, hematuria, weight loss) predominate.

• The more common chronic form of RVT generally is covert.
• The less frequent acute form usually occurs in younger patients, with flank pain and macroscopic hematuria.
• Patients may present with thrombosis and/or embolism.

Physical

Observe for signs of nephrotic syndrome (edema or anasarca).

Causes

• In patients who are nephrotic, the most common underlying nephropathy associated with RVT is membranous nephropathy. For a renal biopsy of membranous nephropathy, see Image 1. The tumor association for RVT is renal cell carcinoma. However, most cases of membranous nephropathy are idiopathic.
• RVT also may be the result of nephrotic syndrome from membranoproliferative glomerulonephritis, minimal change disease, rapidly progressive glomerulonephritis, amyloid, focal sclerosis, or lupus nephritis. RVT is more common in patients with primary rather than secondary nephropathy.
• Findings relative to the causative disease may be present (eg, systemic lupus erythematosus [SLE]/antiphospholipid antibody syndrome, cancer).
• Theories for the putative relationship between nephrotic syndrome and RVT have evolved. Initially, nephrotic syndrome was believed to be a consequence of RVT. However, this presumed sequence was incorrect.
• • Experimentally induced RVT causes only mild proteinuria.
  • RVT in the absence of nephrotic syndrome has been reported in the surgical literature.
  • Nephrotic patients with RVT who have undergone histologic evaluation show evidence of an identifiable glomerulopathy.
  • RVT is known to occur after the onset of nephrotic syndrome. Thus, nephrotic syndrome is not a direct result of RVT but rather leads to RVT.
• SLE also has been associated with RVT.
• • In general, patients with lupus and documented RVT have membranous lupus nephritis (World Heath Organization class V).
  • Generally, thrombophlebitis and circulating anticoagulants (anticardiolipin antibodies) are believed to be much less important than nephrotic syndrome as predisposing factors of RVT in SLE.
• RVT is an uncommon but definite problem in neonates. A possible association exists between RVT and the factor V Leiden mutation in this age group.
• Other diseases or situations that have been associated with RVT include antithrombin III deficiency, protein C or S deficiency, antiphospholipid antibody syndrome, pregnancy or estrogen therapy (all hypercoagulable states), renal vein invasion by malignant cells, post–renal transplantation, Behçet syndrome, and extrinsic compression (eg, lymph nodes, tumor, retroperitoneal fibrosis, aortic aneurysm). Other than renal cell cancer, the other associations are uncommon.
• Trauma, ingestion of oral contraceptive agents, dehydration (infants), and steroid administration also have been associated with RVT.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Renal colic (acute RVT)
Pulmonary embolism from lower extremity veins
Renal papillary necrosis
Loin pain hematuria syndrome
Renal infarction

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No specific lab studies are indicated for RVT except those specific for nephrotic syndrome or other associated factors such as trauma or coexisting hypercoagulable state.
• • Hypercholesterolemia
  • Hypoalbuminemia
  • Serum complement levels
  • Urine protein and loss renal function studies, including serum creatinine and blood urea nitrogen (BUN) - Necessary because RVT may present as unexplained acute renal failure or sudden increase in proteinuria
  • Review of renal biopsy

Imaging Studies

• In RVT, an intravenous pyelogram (IVP) with an abdominal plain film may reveal an enlarged kidney. If the renal pelvis is observed, it usually is distorted. An infrequent but characteristic finding of RVT is notching of the ureter, which occurs when collateral veins near the ureters become tortuous. IVP seldom is used to help make the diagnosis.
• Inferior vena cavography may help provide a diagnosis of RVT. Occasionally, inferior vena cavography is not diagnostic, at which point selective renal vein catheterization can be performed.
• Renal arteriography may be useful in situations in which RVT is secondary to trauma or tumor, in which case renal artery involvement is common.
• Renal ultrasound is a safe noninvasive technique. With underlying RVT, the kidneys swell and become echogenic, with prominent echo-poor medullary pyramids. Color Doppler scanning also may provide information. However, ultrasound usually is not sensitive enough to assist in making the diagnosis.
• CT scan currently is the procedure of choice for diagnosing RVT noninvasively (see Image 2). Intravenous infusion of contrast material assists in visualizing the renal veins. CT scan also demonstrates the presence of renal cell cancer.
• In the future, magnetic resonance imaging (MRI) may become the procedure of choice for the diagnosis of RVT (see Image 3). MRI produces high-contrast images between flowing blood, vascular walls, and surrounding tissue. The major benefit is the avoidance of radiation and intravenous contrast material. MRI also may help detect RVT and the presence of tumor.

Procedures

• Renal biopsy has an essential role in the evaluation of patients who are nephrotic and who have RVT.

Histologic Findings

Renal histologic features of patients who are nephrotic and who have RVT are representative of the responsible primary renal disease. Membranous nephropathy is the most common finding.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Treatment of nephrotic syndrome: Measures may include steroids and immune-suppression therapy. Treatment of underlying renal cell cancer includes surgery for early-stage disease.
• Symptomatic treatment includes diuretics and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) to decrease proteinuria from nephrotic syndrome. If a combination of ACEIs and ARBs lowers protein excretion more than either alone, they should be used together. Decreasing protein loss in the urine decreases hypercoagulability.
• Anticoagulation with warfarin has been recommended in some studies for prophylaxis against pulmonary embolism. Treat hypercholesterolemia according to accepted national guidelines (ie, using appropriate low-density lipoprotein targets for primary or secondary prevention).
• A recent study by Bianchi suggests that atorvastatin decreases the rate of progression of kidney disease, proteinuria, and hypercholesterolemia.

Surgical Care

• Surgical treatment for RVT rarely is used today.
• Surgery has been used in the presence of bilateral RVT or if pulmonary emboli have occurred and anticoagulation is contraindicated. Inferior vena caval filters may be used in this instance.
• Surgery may be necessary for RVT of renal cell cancer, particularly for cure of malignancy.
• Hypernephroma or renal cell cancer is unique in that intraluminal tumor extends into the renal vein and inferior vena cava (IVC) and sometimes extends into the right atrium. In such cases, radical nephrectomy and removal of the tumor from the IVC and right atrium affords the chance of cure. This is not distant metastasis; rather, this is tumor extension within the renal vein and IVC.

Consultations

• Consult a nephrologist and interventional radiologist (only when medical therapy does not prevent pulmonary emboli).
• A surgeon (urologist) can assist in the staging and potential surgery for renal cell carcinoma (early-stage disease).
• A combined team that consists of a urologist, vascular surgeon, cardiac surgeon, transplant surgeon, or a combination thereof works together in complex cases of renal cancer with extension into renal vein, IVC, and right atrium.

Diet

• Many nephrologists recommend normal protein intake for patients with nephrotic syndrome.
• Protein restriction may be used with benefit (Maroni, 1998) in patients who are nephrotic who do not spill massive amounts of protein (approximately 10 g or more over 24 h) or in those who have chronic renal failure.

Activity

Activity is allowed as tolerated.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Reduction in proteinuria is essential in the treatment of RVT in patients who are nephrotic. The current standard is ACE inhibition and/or 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 to anticoagulation. In pulmonary embolic disease from other causes, thrombolytics are indicated in the setting of pulmonary hypertension (as found during examination or discovered by echocardiography).

Warfarin, ARBs, and ACEIs are unsafe in pregnancy. Patients with RVT in pregnancy are treated best with heparin alone.

Drug Category: Angiotensin-converting enzyme inhibitors

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.

Drug Category: Angiotensin receptor blockers

Reduce urine protein excretion by decreasing glomerular hydraulic pressure.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Further inpatient care is as needed for loss of renal function or for the treatment of pulmonary emboli.

Further Outpatient Care

• Further outpatient care is as needed for loss of renal function or for the treatment of pulmonary emboli.

In/Out Patient Meds

• For nephrotic syndrome, see Medical Care. The primary abnormality in nephrotic syndrome is excessive urinary protein loss. Urinary protein is injurious to the renal tubules.
• For pulmonary emboli, see Medical Care.
• ACEIs and ARBs decrease urine protein through an effect on efferent arteriolar pressure. Titrate to as high a dose as tolerated. If protein loss decreases, hypercoagulability improves.
• Atorvastatin
• Cyclosporine has demonstrated benefit in early trials for treatment of membranous nephropathy. A cure of the underlying nephropathy reverses nephrotic syndrome and RVT.

Transfer

• For thrombolytics or interventional radiology, transfer patients especially if a vena caval filter is necessary in the event of failure of medical therapy for recurrent thromboembolism. The vena cava filter in these cases has to be placed above the level of renal veins (suprarenal IVC filter). This is unique because, in all other forms of DVT and pulmonary embolism, IVC filters are placed in the infrarenal segment of the IVC. Either the interventional radiologist or the vascular surgeon can perform this.

Complications

• Recurrent thromboembolic phenomena
• Renal failure
• Metastasis from renal cell cancer
• Problems specific to etiologic cause (eg, graft failure after renal transplantation)

Prognosis

• Prognosis of any glomerular disease may be worsened by superimposition of acute RVT, but whether the slow development of chronic RVT accelerates renal functional loss is uncertain.
• The negative prognosis of RVT is related to pulmonary embolic events. If RVT is secondary to cancer, it may signal dissemination of the malignancy.
• Graft survival after transplantation is adversely affected by RVT.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Missing RVT as the source for pulmonary emboli is a medical/legal pitfall.
• When a patient presents with pulmonary embolism (PE) and no evidence of lower extremity deep vein thrombosis (DVT), the patient should be examined for renal vein thrombosis and renal cancer. Renal cell cancer (hypernephroma) is unique in that it may cause PE by 2 mechanisms. The first is an increased secretion of erythropoietin, which increases blood viscosity and hypercoagulability, causing DVT and PE. The other mechanism is tumor extension into the renal vein and IVC (tumor thrombus), which may break loose and cause PE.
• Avoid use of warfarin (Coumadin) for RVT during pregnancy. Heparin should be used instead.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  This renal biopsy shows membranous nephropathy. Light (hematoxylin and eosin) stain shows thickened capillary loops via electron microscopy, with subepithelial deposits.
	View Full Size Image
Media type:  Photo

Media file 2:  This CT scan shows renal vein thrombosis secondary to renal cell cancer. The arrow is pointed at the thrombosed renal vein.
	View Full Size Image
Media type:  CT

Media file 3:  This MRI is from a patient with renal cell cancer and renal vein thrombosis. The arrow is on the thrombosed vein.
	View Full Size Image
Media type:  MRI

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Babu SC, Manoni T, Shah PM. Malignant renal tumor with extension to the inferior vena cava. The American Journal of Surgery. 1998;176:137 -139.
• Bianchi S, Bigazzi R, Caiazza A, Campese VM. A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis. Mar 2003;41(3):565-70. [Medline].
• Borrello JA. Renal MR angiography. Magn Reson Imaging Clin N Am. Feb 1997;5(1):83-93. [Medline].
• Irish AB, Green FR, Gray DW, Morris PJ. The factor V Leiden (R506Q) mutation and risk of thrombosis in renal transplant recipients. Transplantation. Aug 27 1997;64(4):604-7. [Medline].
• Kim HS, Fine DM, Atta MG. Catheter-directed Thrombectomy and Thrombolysis for Acute Renal Vein Thrombosis. J Vasc Interv Radiol. May 2006;17(5):815-22.
• Markowitz GS, Brignol F, Burns ER, et al. Renal vein thrombosis treated with thrombolytic therapy: case report and brief review. Am J Kidney Dis. May 1995;25(5):801-6. [Medline].
• Maroni BJ. Protein restriction in the pre-end-stage renal disease (ESRD) patient: who, when, how, and the effect on subsequent ESRD outcome. J Am Soc Nephrol. Dec 1998;9(12 Suppl):S100-6. [Medline].
• Meehan SM, Limsrichamrern S, Manaligod JR, et al. Platelets and capillary injury in acute humoral rejection of renal allografts. Hum Pathol. Jun 2003;34(6):533-40. [Medline].
• Nickolas TL, Radhakrishnan J, Appel GB. Hyperlipidemia and thrombotic complications in patients with membranous nephropathy. Semin Nephrol. Jul 2003;23(4):406-11. [Medline].
• Orth SR, Ritz E. The nephrotic syndrome. N Engl J Med. Apr 23 1998;338(17):1202-11. [Medline].
• Zini L, Haulon S, Leroy X, et al. Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with retro- or suprahepatic caval thrombus. BJU Int. Jun 2006;97(6):1216-20.

Article Last Updated: Jun 9, 2006