Renal Vein Thrombosis

Etiology

The most common etiology is nephrotic syndrome as it results in a hypercoagulable state. In patients who are nephrotic, the most common underlying nephropathy associated with RVT is membranous nephropathy, followed by minimal change disease, and membranoproliferative glomerulonephritis.[5] Other common systemic and local causes of RVT are as follows:  

Systemic

• Primary hypercoagulability disorders (e.g., antithrombin III deficiency, protein C or S deficiency, factor V Leiden mutation, prothrombin G20210A mutation)
• Antiphospholipid syndrome
• Postrenal transplant/allograft rejection
• Renal vasculitis
• Sickle cell nephropathy[6]
• Systemic lupus erythematosus (SLE)
• Amyloidosis
• Diabetic nephropathy
• Pregnancy or estrogen therapy
• Behcet syndrome
• Severe dehydration or prolonged hypotension (especially in neonates)

Local

• The malignant renal tumors, typically renal cell carcinoma that extends into the renal veins, are associated with thrombus in 4% to 25% of cases.[7]
• Extrinsic compression of the renal vein or IVC due to a tumor, lymph nodes, retroperitoneal disease, or an aortic aneurysm
• Blunt abdominal trauma or trauma during venography

Epidemiology

There is scarce data on the exact US prevalence of RVT in adults as it is often asymptomatic with spontaneous resolution. There is also a high degree of variability as the reported number of cases of RVT in patients with nephrotic syndrome, and membranous nephropathy is 5% to 60%.[8]

In intrauterine life, RVT can occur mostly in the presence of factor V Leiden.[9] In neonates,  RVT is one of the most frequent causes of venous thrombosis and usually follows severe dehydration or prolonged periods of hypotension.[10]

No specific numbers are available for the frequencies of RVT by gender. However, since RVT is commonly associated with membranous nephropathy, a male predominance is reported. This is because membranous nephropathy has a 2:1 male to female ratio. Similarly, age is a factor in RVT only to the extent as any age-related risk of glomerular disease, for example, membranous nephropathy peaks in the fourth through the sixth decade, making RVT likely in this specific age group). Lastly, there is no racial predilection.

Pathophysiology

The pathogenesis of RVT is based on Virchow’s triad which is due to one or more of the following:

• Vascular endothelial damage due to an injury of the vessel wall or in cases of homocystinuria where high levels of homocysteine cause spontaneous microtrauma to the endothelium
• Stasis of blood flow, for example, in severe dehydration/volume depletion in infants
• A hypercoagulable state such as in patients with a nephrotic syndrome where excessive urinary protein loss, decreased antithrombin III levels, a relative excess of fibrinogen, and changes in other clotting factors; all leads to the propensity of a clot

Histopathology

Microscopic examination of renal biopsy in cases of RVT reflects findings of the primary renal disease responsible for the thrombosis. For example, patients who are nephrotic and have RVT will most commonly have histological findings of membranous nephropathy as it is the most common underlying association.

History and Physical

Clinical presentation of renal vein thrombosis varies by the rapidity of venous occlusion and development of venous collaterals. Chronic RVT has an insidious onset and is usually asymptomatic. Rarely, it may present as peripheral edema.

Acute renal vein thrombosis usually presents with symptoms of renal infarction, including flank pain, flank tenderness, rapid deterioration of renal function and worsening proteinuria, micro or macroscopic hematuria. Nausea, vomiting or fever may be present.

In a renal transplant, RVT usually presents within 48 hours of surgery manifesting as sudden anuria and tenderness over the transplanted kidney.

In neonates and infants, acute RVT may present with gross hematuria, flank mass, signs and symptoms of dehydration or shock, and oligo-anuria.

Left-sided RVT can lead to gonadal vein thrombosis manifested as pelvic congestion syndrome in females and whereas in males with painful swelling of the left testis and varicocele.

Evaluation

Most often, RVT has an insidious onset, producing minimal to no symptoms, and is usually diagnosed incidentally during imaging for some other reason. Renal venography is the gold standard diagnostic test for RVT and has the additional advantage of a therapeutic procedure. However, it is rarely used in current practice due to the availability of lesser invasive tests. Renal ultrasonography(USG) is a safe, non-invasive test, though it is usually not sensitive enough to make a diagnosis of RVT. Renal USG shows an enlarged kidney and hyper-echogenic kidney in approximately 90% of the patients in the early phase of acute RVT.[11] Color Doppler or contrast-enhanced ultrasonography may yield better results. Computed tomography (CT) angiography is the test of choice for diagnosing RVT which can demonstrate thrombus in the renal vein and, at times, in the vena cava. The sensitivity and specificity of CT angiography are almost 100%.[12] Contrast-enhanced, magnetic resonance venography (3D-CE-MRV) is as sensitive as CT and has the major benefit of avoidance of radiation and intravenous (IV) contrast. Both CT and MRV can help detect RVT as well as the presence of renal cell cancer.

No specific laboratory studies are indicated for renal vein thrombosis (RVT), except those specific for the underlying etiology (e.g., for nephrotic syndrome or coexisting hypercoagulable state).

Treatment / Management

Generally, RVT is considered as a result of an underlying kidney disease rather than its cause. Therapy is therefore directed at the treatment of the underlying disorder (most commonly nephrotic syndrome) and supporting renal function.

Although no randomized trials exist to evaluate the role of anticoagulation therapy in asymptomatic RVT, anticoagulation therapy should be provided to prevent the risk of progression of thrombus or occurrence of an embolic event. Patients with symptomatic RVT (such as acute RVT) should be treated similarly to patients who have Pulmonary embolism (PE) or deep venous thrombosis (DVT). Typically, initial treatment includes starting unfractionated or low-molecular-weight heparin and then bridged to warfarin, for a goal INR of 2 or 3. Direct thrombin inhibitors and factor Xa inhibitors have not been studied in nephrotic patients with RVT and are not recommended for anticoagulation. Patients with documented RVT and pulmonary embolism who have contraindications for anticoagulation can be effectively treated with suprarenal IVC filters. Anticoagulation is generally given for 6 to 12 months, though most recommendations are to continue as long as a patient remains nephrotic.

Systemic fibrinolysis carries a risk of significant life-threatening bleeding and is usually not recommended. Local thrombolytic therapy with or without catheter-directed thrombectomy in patients with acute RVT is associated with acute renal failure. Surgical thrombectomy can be rarely considered in the setting of acute bilateral RVT and acute renal failure especially if percutaneous thrombectomy and/or thrombolysis cannot be performed.

Differential Diagnosis

Acute RVT presenting with loin pain and hematuria can mimic renal colic, pyelonephritis, renal papillary necrosis, or renal infarction from renal artery thrombosis or embolism. Renal cyst in adult polycystic kidney disease is another condition to consider. Rarely, a tumor thrombus (extension of a tumor into the vein) may be confused with RVT.

Prognosis

Prognosis is favorable with treatment. However, the morbidity and mortality of RVT depend on its underlying cause. For example, in cases of RVT secondary to malignancy, complications can arise from the malignancy itself or result in thromboembolism at other sites such as DVT or PE. Prognosis of RVT due to nephrotic syndrome as per a retrospective cohort study showed a 40% mortality at 6 months in 27 patients with RVT.[13] Survivors appeared to have stable renal function and resolution of nephrotic syndrome. RVT that develops after a renal transplant has a poor prognosis and usually results in graft failure, particularly in the first month post-transplant.[14] 

Complications

Complications include a decline in renal function, leading to chronic kidney disease with a potential to lead to end-stage renal disease. Renal atrophy, hypertension, or extension of thrombus/embolism may occur. Left-sided renal vein thrombosis may cause pelvic congestion syndrome in females and swelling of left testis or varicocele in males. RVT after renal transplant usually occurs early after the surgery and has a reported prevalence of 0.1% to 4.2% and ultimately leads to loss of graft in almost all cases.[15]