Adonteng A. Kwakye, MD
BASICS
DESCRIPTION
• Renal vein thrombosis (RVT) is an acute or chronic thrombosis in the renal vein leading to a reduction in venous drainage of the kidney.
• In infants, RVT typically presents as a severe illness, occasionally with colicky pain:
– 60% have enlarged kidneys on physical exam; gross hematuria and microangiopathic hemolytic anemia and thrombocytopenia can also be present
• In the adult, RVT presentation depends on onset of RVT:
– Acute RVT: Triad of sudden flank pain
– Costovertebral angle tenderness and gross hematuria only present in minority of cases.
– Chronic RVT: Generally asymptomatic;
Can have proteinuria and microscopic or gross hematuria.
EPIDEMIOLOGY
Incidence
• Newborns and infants:
– Commonly associated with hypoxia, dehydration, shock, and/or sepsis
– Usually acute and unilateral (more common on the left side); although 30% bilateral
– Male-to-female ratio 2:1 in the neonate, with no sex predilection beyond age 1
– Accounts for approximately 10% of venous thrombosis in newborns
– Most common form of thrombosis not associated with a vascular catheter (1)
• Adults:
– Associated with nephrotic syndrome (reported incidence of RVT in patients with nephrotic syndrome ranges from 5–62%), renal cell carcinoma, or renal transplantation
– More often chronic and unilateral
Prevalence
N/A
RISK FACTORS
• Newborn/infant:
– Acute hypoxia
– Birth trauma
– Cyanotic congenital heart disease with polycythemia
– Cytomegalovirus infection
– Dehydration from diarrhea/vomiting
– Maternal diabetes, polyhydramnios
– Hyperosmolar state form angiocardiography
– Preterm (<36 wk) infants at greater risk
– Sickle cell disease
• Adult:
– Abdominal tumors, especially renal cell carcinoma
– Endothelial damage
– Intrinsic hypercoagulability (eg, Factor V Leiden deficiency)
– Nephrotic syndrome:
– Membranous nephropathy: Lesion most frequently associated with nephrotic syndrome–related RVT; also reported in many other nephropathies.
– Use of oral contraceptives, steroids
– Renal transplantation, particularly in those taking OKT-3 and cyclosporine for immunosupression
– Shock, sepsis, dehydration
– Trauma
– Use of IV contrast agents
– Vasculitis
– Compression from aortic aneurysm, lymphadenopathy, retroperitoneal fibrosis (2)
Genetics
Unknown
PATHOPHYSIOLOGY
• Newborn/infant:
– Diminished intrarenal blood flow due to hypovolemia (sepsis, dehydration, diarrhea)
– Creates prothrombotic state
– Clot can then propagate in antegrade and/or retrograde manner, resulting in RVT
– May become bilateral, produce vena caval occlusion and/or renal artery thrombosis
– 65% in neonates, 30% beyond 1 yr age
– Associated with adrenal hemorrhage in 15% of cases
• Adults: Most often unilateral; acute and chronic forms described:
– Acute RVT: Severe dehydration, sudden hypercoagulability, renal vein obstruction from tumor or transplant rejection
– Chronic RVT:
Nephrotic syndrome leads to alterations in coagulation pathway that creates prothrombotic conditions (3)
RVT is a result of nephrotic syndrome and not the cause
Slow onset allows the development of collateral venous kidney drainage
ASSOCIATED CONDITIONS
• DVT in patients with nephrotic syndrome
• Pulmonary embolus
GENERAL PREVENTION
• Adults: Long-term anticoagulation is appropriate if RVT has recurred when patients discontinued anticoagulation
• Treatment of underlying cause
DIAGNOSIS
HISTORY
• Newborn/infant:
– Risk factors: Mother’s history, birth, and early postnatal course
– Gross hematuria
• Adult:
– Sudden onset of hematuria and flank pain should raise the question of RVT, as should a history of nephrotic syndrome in the presence of hematuria
PHYSICAL EXAM
• Newborn/infant:
– Unilateral, or often bilateral, flank masses
– Evidence of dehydration
– Evidence of cyanotic heart disease
– If the thrombosis is bilateral, oliguria may be present; urine output may be normal with a unilateral thrombus (4)
• Adult:
– Evidence of blunt trauma, abdominal mass
– Edema or anasarca suggestive of nephrotic syndrome
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Newborn/infant:
– Thrombocytopenia, leukocytosis, hemolytic anemia
– Consumptive coagulopathy (prolonged clotting time, elevated fibrinogen and fibrin split products)
– Proteinuria
– Elevated BUN and creatinine
• Adult:
– Proteinuria and microscopic hematuria
– Hemolytic anemia, consumptive coagulopathy, and thrombocytopenia may be present
– Elevated BUN and creatinine
– Hypoalbuminemia
– Marked elevation in LDH with normal transaminases
Imaging
• Newborn/infant:
– The extent of thrombus may be assessed by duplex ultrasonography, and only rarely will CT, MRI, or renal venography be required for confirmation of the diagnosis or determination of the extent of thrombus
– Ultrasonography: Enlarged and echogenic kidneys (90%) with attenuation or loss of corticomedullary differentiation
Doppler studies may detect increased resistance or absence of flow in renal venous branches; increased resistance in the renal artery may be present
Doppler ultrasonography is the primary modality for the detection of RVT; however, its utility is operator specific (3)
– IVP: Delayed opacification and renomegaly
– A renal scan may be obtained to assess the function of the involved kidney.
– MRI is more expensive and requires sedation in pediatric patients (6)
• Adult:
– Inferior vena cavography with selective catheterization of the renal vein is the gold standard for the diagnosis.
– CT findings are similar in noninvasive evaluation of acute RVT.
Sensitivity of CT angiography approaches 100%; considered current imaging modality of choice
Low attenuation within the renal vein; proximal venous enlargement
Capsular venous collaterals, thickened Gerota’s fascia and pericapsular stranding
– Doppler ultrasonography is helpful, especially in a transplanted kidney.
– MRI: Excellent imaging; avoids iodinated contrast, but concerns with gadolinium in patients with renal insufficiency
– IVP
Faint or absent excretion of contrast
Enlarged kidney due to congestion
Collateral circulation may cause collecting system opacification and/or notching of ureter
Renal pelvis is often distorted
Diagnostic Procedures/Surgery
Renal biopsy in the setting of nephrotic syndrome and RVT confirms etiology and may guide therapy
Pathologic Findings
• Membranous nephropathy is the most common finding in the setting of nephrotic syndrome and RVT.
• In infants the condition is pathologically more correctly described as “renal venous thrombosis” as the interlobular and arcuate renal veins are primarily affected rather than the main renal vein in adults.
DIFFERENTIAL DIAGNOSIS
• Other causes of flank pain (eg, urolithiasis, pyelonephritis, renal infarction)
• Renal cell carcinoma with direct compression or tumor thrombus
• Renal vein leiomyosarcoma (filling defect)
TREATMENT
GENERAL MEASURES
• Evaluate and treat all underlying causes
• Aggressive rehydration and treatment of sepsis, diarrhea, and electrolyte abnormalities
MEDICATION
First Line
• Newborn/infant:
– Use of thrombolytic agents is reported, but controversial
– Systemic heparinization:
Prevents thrombus propagation into vena cava (risk of propagation low with fluid and electrolyte repletion).
Used in neonates with bilateral RVT
Equivocal results regarding long-term preservation of renal function
• Adult:
– Unilateral RVT: Heparin anticoagulation and long-term anticoagulation with warfarin:
– Optimum duration of anti-coagulation unknown
– Most experts feel that warfarin should be continued for as long as nephrotic syndrome persists (3).
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Infants: No role for surgical thrombectomy
• Thrombectomy in adults:
– Rarely used, because neither renal preservation nor improvement in survival demonstrated
– Surgical thrombectomy (either open or percutaneous) in patients with acute bilateral RVT with poor prognosis
– Postoperative posttransplant RVT
• Nephrectomy in highly selected patients for lifesaving measures
• Radical nephrectomy and thrombectomy in renal cell carcinoma
ADDITIONAL TREATMENT
• Infants with renal failure—dialysis if needed
• IVC filters are indicated in high-risk adult patients for pulmonary embolism.
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Neonates: Mortality rate of 3%
• The kidney may recover completely, atrophy, or recover partially, resulting in renovascular hypertension or chronic tubular dysfunction.
• Nephrectomy may be required if renovascular hypertension or chronic infection develops.
• ACE inhibitors and/or angiotensin II receptor blockers may decrease proteinuria from nephrotic syndrome as decreased urinary protein loss decreases hypercoagulability.
COMPLICATIONS (5)
• Consumptive coagulopathy
• Pulmonary embolism
• Renal failure
• Loss of graft in transplant patient
FOLLOW-UP
Patient Monitoring
• Newborn/infant:
– Renal function may be followed using nuclear scanning. Atrophy is often detected long term. About 5% of affected neonates progress to dialysis or transplantation.
– Monitor blood pressure, as renovascular hypertension may occur after RVT in ∼20%, even with normal renal function.
• Adult:
– Treat cause of nephrotic syndrome
– Long-term anticoagulation as preventive measure in nephrotic syndrome not supported
– Because RVT may be asymptomatic, all patients with nephrotic syndrome should be monitored for symptoms of RVT
Patient Resources
MedlinePlus: Renal vein thrombosishttp://www.nlm.nih.gov/medlineplus/ency/article/000513.htm
REFERENCES
1. Schmidt B, Andrew M. Neonatal thrombosis: Report of a prospective Canadian and international registry. Pediatrics. 1995;96:939–943.
2. Ferri F. Ferri’s clinical advisor 2013. R - Renal vein thrombosis. 1st ed. Philadelphia, PA: Elsevier; 2013.
3. Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Throm Res. 2006;118:397–407.
4. Lum GM. Kidney & urinary tract. In: Hay WW Jr., Levin MJ, Deterding RR, et al., eds. Current Diagnosis & Treatment: Pediatrics. 21st ed. Chapter 24. New York, NY: McGraw-Hill; 2012.
5. Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome.Kidney Int. 1985;28(3):429–439.
6. Textor SC, Leung N. Chapter 286. Vascular injury to the kidney. In: Longo DL, Fauci AS, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012.
ADDITIONAL READING
• Asghar M, Ahmed K, Shah SS, et al. Renal vein thrombosis. Eur J Vasc Endovasc Surg. 2007;34(2):217–223.
• Lau KK, Stoffman JM, Williams S, et al. Neonatal renal vein thrombosis: Review of the English-language literature between 1992 and 2006. Pediatrics. 2007;120(5):e1278–e1284.
See Also (Topic, Algorithm, Media)
• Nephrotic Syndrome
• Renal Cell Carcinoma with Tumor Thrombus
• Renal Vein Thrombosis, Adult and Pediatric Image 
• Renal Vein, Leiomyosarcoma
CODES
ICD9
• 453.3 Other venous embolism and thrombosis of renal vein
• 581.9 Nephrotic syndrome with unspecified pathological lesion in kidney
• 788.0 Renal colic
ICD10
• I82.3 Embolism and thrombosis of renal vein
• N04.9 Nephrotic syndrome with unspecified morphologic changes
• N23 Unspecified renal colic
CLINICAL/SURGICAL PEARLS
• Renal vein thrombosis (RVT) is associated with nephrotic syndrome in adults.
• Membranous nephropathy is most common pathology in RVT with nephrotic syndrome.
• Newborns and infants more likely than adults to have bilateral RVT.