Renal Vein Thrombosis


Article Author:
Hiba Mazhar


Article Editor:
Narothama Reddy Aeddula


Editors In Chief:
Vijay Lapsia


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
12/26/2018 8:47:17 PM

Introduction

Renal vein thrombosis (RVT), the presence of thrombus in the major renal veins or its tributaries, is a rare clinical entity. It can present acutely or go unnoticed and can result in acute kidney injury or chronic kidney disease. Rayer, a French nephrologist, was the first to describe RVT and its association with proteinuria in the 1840s.[1]

It is commonly associated with nephrotic syndrome, primary hypercoagulability disorders, malignant renal tumors, extrinsic compression, infections, trauma, or as a post-renal transplant complication.[2][3] Almost two-thirds of patients have bilateral renal vein involvement. The left renal vein is more commonly involved due to its extensive venous network compared to the right. Thrombosis may extend from the vena cava into the peripheral venules or may originate in the peripheral veins and propagate to the main renal vein.[4] The severe passive congestion that develops causes the kidney to swell and become engorged, leading to degeneration of nephrons and causing symptoms of flank pain, hematuria and decreased urine output.

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 the intrauterine life, RVT can occur mostly in the presence of factor V Leiden.[9] In the 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 the 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 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 is 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 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, 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 a 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]

Consultations

  • Nephrology
  • Vascular medicine
  • Urology
  • Hematology/Oncology
  • Radiology

Deterrence and Patient Education

RVT is usually asymptomatic; however, patients are advised to seek medical attention immediately if they experience flank pain, blood in the urine, decrease urine output, or difficulty breathing. Patients who are known to have underlying renal disease, post-renal transplant or prone to hypercoagulability should be particularly aware of these symptoms.

Pearls and Other Issues

  • Renal vein thrombosis (RVT), the presence of thrombus in the major renal veins or its tributaries, is a rare clinical entity.
  • Males are affected more commonly than females with no racial predilection.
  • Clinical manifestations vary by the rapidity of the venous occlusion.
  • Most common etiology is nephrotic syndrome, though can be seen with primary hypercoagulability disorders, malignant renal tumors, infections, trauma or as a post-renal transplant complication.
  • CT angiography is almost 100% sensitive and specific to diagnose RVT.
  • Anticoagulation is provided to prevent complications such as acute kidney injury or chronic kidney disease.
  • RVT carries a favorable prognosis though outcomes depend on the underlying etiology.

Enhancing Healthcare Team Outcomes

Patients diagnosed with RVT may require consultation and coordination of care with vascular medicine, nephrology, urology, and radiology. Membranous nephropathy is the most common biopsy proven subtype of nephrotic syndrome associated with RVT. It is also found to be an independent risk factor for increased risk of thromboembolic events.[16] (Level IV) Since a majority of cases of RVT are asymptomatic, clinicians should maintain a high index of suspicion, especially in patients with nephrotic syndrome and should have a low threshold for diagnostic work-up to improve detection rates and prevent the occurrence of further thromboembolic events.

Clinicians, nurses, and pharmacists should work together as an interprofessional team to educate and support patients with RVT. (Level V)


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Renal Vein Thrombosis - Questions

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A 37-year-old female complains of a 2-week history of right-sided flank pain, bilateral lower extremity edema, and polyuria. She has no past medical history, takes no medications, and does not report smoking, or the use of alcohol or illicit drugs. Her vital signs are normal. Her examination is only remarkable for 2+/4 pitting pedal edema. There are 3.5 g of protein in the 24-hour urine collection. Creatinine is 0.8 mg/dL. The ultrasound shows the right kidney is 13.5 cm, and the left kidney is 11.5 cm. What imaging test would be best to perform next for this patient?



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A 25-year-old male with nephrotic syndrome, membranous subtype, presents with acute onset of right flank pain and gross hematuria which started one day before presentation. He states that this is the first time he has had these symptoms. He does not have any other complaints. He is vitally stable, and examination is unremarkable except for 2+ pitting edema present bilaterally on the lower limbs. Routine laboratory studies are within normal limits. Urinalysis showed 3+ proteinuria and 3+ RBCs. His current medications include losartan, cyclosporine, and prednisone. Which of the following investigations will most likely lead to the correct diagnosis?



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A 55-year-old male is presenting for follow up after recently being diagnosed with non-small cell lung cancer. He has no new complaints on this visit. No prior medical or surgical history and does not take any medications. He continues to smoke one pack per day for past 30 years. Staging workup for his cancer reveals a normal MRI of the brain. Contrast-enhanced CT of abdomen and pelvis does not reveal any evidence of distant metastasis but a left renal vein thrombus extending to the inferior vena cava. Both kidneys appear normal in size. Routine labs including complete blood count, renal and liver function panel are unremarkable. INR is 1. Urinalysis and microscopy are unremarkable. Which is the best treatment option for the patient’s renal vein thrombus?



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A 37-year-old lady undergoes deceased donor renal transplant for reflux nephropathy on the right. She does not have any prior history of nephrolithiasis. Preoperative serum creatinine is 4.0 mg/dL (eGFR 18 ml/hr). Induction therapy with basiliximab was given, and immunosuppression with a combination of tacrolimus, mycophenolate, and prednisone was given. Postoperatively, the patient has brisk urine output and progressive fall in serum creatinine (serum creatinine 2.0 mg/dL, eGFR 66 ml/hr). Doppler ultrasound of transplanted kidney showed resistive index (RI) of 0.67. On postoperative day 3, the patient has sudden, severe right-sided abdominal pain, hematuria, and oliguria with urine output 300 cc over 24 hours. Ultrasound Doppler of allograft showed reverse diastole in segmental arteries with an absence of venous flow. What is the likely cause of graft failure?



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Renal Vein Thrombosis - References

References

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Llach F, Thromboembolic complications in nephrotic syndrome. Coagulation abnormalities, renal vein thrombosis, and other conditions. Postgraduate medicine. 1984 Nov 1     [PubMed]
Gauthier M,Canoui-Poitrine F,Guéry E,Desvaux D,Hue S,Canaud G,Stehle T,Lang P,Kofman T,Grimbert P,Matignon M, Anticardiolipin antibodies and 12-month graft function in kidney transplant recipients: a prognosis cohort survey. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018 Jan 16     [PubMed]
Dimitroulis D,Bokos J,Zavos G,Nikiteas N,Karidis NP,Katsaronis P,Kostakis A, Vascular complications in renal transplantation: a single-center experience in 1367 renal transplantations and review of the literature. Transplantation proceedings. 2009 Jun     [PubMed]
Asghar M,Ahmed K,Shah SS,Siddique MK,Dasgupta P,Khan MS, Renal vein thrombosis. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2007 Aug     [PubMed]
Aeddula NR,Baradhi KM, Sickle Cell Nephropathy . 2018 Jan     [PubMed]
Zigman A,Yazbeck S,Emil S,Nguyen L, Renal vein thrombosis: a 10-year review. Journal of pediatric surgery. 2000 Nov     [PubMed]
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