Renal Vein Thrombosis

　　I. Etiology

　　The common causes of renal vein thrombosis include two types of diseases: one is hypercoagulable state of blood, common diseases that cause hypercoagulable state include nephrotic syndrome; severe dehydration in infants and young children; pregnancy or oral contraceptives; congenital thrombosis such as congenital deficiency of antithrombin III, congenital protein C deficiency, etc.; systemic lupus erythematosus, myelofibrosis, etc. The other is venous wall damage, common diseases that cause venous wall damage include renal cell cancer invasion of renal vein; renal trauma; compression of renal vein by adjacent organ tissue lesions, such as enlarged lymph nodes, abdominal aortic aneurysm, etc.

　　II. Pathogenesis

　　The occurrence mechanism of renal vein thrombosis mainly includes excessive synthesis and insufficient inactivation of coagulation factors, decreased activity of the fibrinolytic system, increased platelet count, enhanced platelet activity, and abnormal function of vascular endothelial cells. These factors often coexist, influence each other, and interact with each other, being in an extremely complex dynamic change. The following takes nephrotic syndrome as an example to explore the mechanism of renal vein thrombosis formation.

　　1. Coagulation and anticoagulation systems:In nephrotic syndrome, a large amount of protein is excreted with urine and lost, especially small molecular weight proteins. Anticoagulant substances such as antithrombin III, protein C, protein S, and antiprotease have small molecular weights (54,000-69,000 Da) and are easy to be excreted with urine, causing a decrease in anticoagulant activity. While coagulation factors V, VII, VIII, and coagulation factor I are large molecular weight proteins (200,000-800,000 Da) and are not easily excreted by the kidneys, they can increase with compensatory increase in liver synthesis, enhancing coagulation activity.

　　2. Fibrinolysis system:The normal activity of the fibrinolytic system is dynamically balanced with the coagulation system to prevent the occurrence of hemorrhage or thrombosis. In patients with nephrotic syndrome, there is excessive loss of plasminogen (with a small molecular weight), while fibrinolytic inhibitors (such as α2-macroglobulin, etc.) are difficult to be excreted from the urine due to their large molecular weight, resulting in increased plasma concentration and increased inactivation of plasmin. Therefore, the fibrinolytic activity decreases in nephrotic syndrome, making it prone to thrombosis.

　　3. Other factors leading to hypercoagulability:The platelet count of some patients with nephrotic syndrome can increase or be normal, and some patients also show enhanced platelet aggregation function, which may also be related to the decrease in plasma protein content and the increase in blood lipids. The specific mechanism is not yet clear. Clinically, excessive diuresis increases blood viscosity, aggravating the hypercoagulable state; long-term and large amounts of corticosteroid treatment stimulate platelet production, increase the content of some coagulation factors, and further aggravate the hypercoagulable state. Due to interstitial and intracellular edema in patients with nephrotic syndrome, the function of vascular endothelium is damaged, and the balance between prostacyclin and thromboxane A2 (TXA2) in endothelial cells is disrupted, which is conducive to the formation of thrombosis.

　　In summary, the imbalance of coagulation and fibrinolysis, this pair of contradictions, will make the body prone to thrombosis, whether it is nephrotic syndrome or renal vein thrombosis caused by other reasons, they are more or less related to the above pathogenesis. Understanding the mechanism of renal vein thrombosis formation is conducive to our understanding of the occurrence of its clinical manifestations and further guiding treatment.

　　The main complications are acute renal failure and pulmonary embolism, and some patients may have complications such as hypertensive crisis.

　　1. Infection:The immunity of patients with nephrotic syndrome is reduced, and they are prone to infection. Common infections include respiratory tract infections such as pharyngitis, tonsillitis, pneumonia, and urinary tract infections. Due to malnutrition, hair loss, brittle nails, slow growth and development in children, and abdominal pain, primary pleurisy may occur. Once infection occurs, it should be treated immediately, otherwise it is easy to lead to death.

　　2. Thrombosis, embolic tendency:When patients have nephrotic syndrome, the blood is in a relatively easy to coagulate state. When the plasma protein is less than 20 grams per liter, the risk of renal vein thrombosis formation increases. Thrombus detachment can cause pulmonary embolism, and thrombi can appear in the arteries and veins of the body's organs.

　　3. Acute renal failure.

　　The clinical manifestations of this disease have a great individual difference, varying with the severity and urgency of RVT occurrence. Acute complete renal vein thrombosis is more common in children, due to the lack of sufficient collateral circulation formation, the clinical manifestations are chills, fever, severe lumbar costal pain and abdominal pain, obvious tenderness over the costovertebral angle, renal area percussion tenderness, elevated blood leukocytes, hematuria, and loss of function of the diseased kidney. Imaging can show kidney enlargement. If both renal veins are thrombosed, or if one kidney has no function due to thrombosis and the other kidney vein thrombosis occurs, oliguria and acute renal failure may occur. In patients with nephrotic syndrome, pregnancy, oral contraceptives, etc., the age of the patients is usually younger, and they often have acute or rapidly progressive renal function deterioration of unknown cause, accompanied by progressive worsening of proteinuria and hematuria, leading to suspicion and further examination to find RVT. In older people, if thrombosis occurs slowly, the collateral circulation is fully established, and the renal function damage is not significant, the clinical manifestations may only be recurrent pulmonary embolism or embolism in other parts of the body. Some patients may develop hypertension, lower limb edema. All RVT patients, if the inferior vena cava is involved, can develop inferior vena cava obstruction syndrome, with lower limb edema and the formation of venous collateral circulation in the abdominal wall. The most serious complication of renal vein thrombosis is pulmonary embolism, about half of the chronic renal vein thrombosis patients have pulmonary embolism, and it is often the first symptom.

　　Patients with nephrotic syndrome, due to the high coagulability of blood, are prone to thrombosis formation, and their clinical manifestations also have a great individual difference. RVT may not have any special clinical manifestations, but may also have certain clinical symptoms such as fever (17%), acute lumbago (10% to 64%), tenderness and percussion tenderness over the renal area, sudden onset of hematuria (74%), increased blood creatinine, B-ultrasound examination showing kidney enlargement (43%). When these symptoms are found in patients with nephrotic syndrome, one should be aware of the possibility of RVT, but most (75%) RVTs do not have typical clinical manifestations (chronic type or subclinical type), and there is no obvious relationship with the fluctuation of nephrotic syndrome. Therefore, it is difficult to make a diagnosis for these RVTs.

　　1. Promoting blood circulation:Encourage patients to increase their activity, and assist patients in turning over at regular intervals if necessary, paying attention to active or passive limb movements, such as voluntary extension and flexion of the limbs, or massaging the leg muscles, 4 times a day, each session lasting 10 minutes, to promote venous return.

　　2. Avoiding blood stasis:For high-risk patients, including elderly, obese, postoperative, or immobilized patients, elastic stockings or elastic socks should be worn on both lower limbs immediately after the operation to promote blood return; avoid placing a hard pillow under the knee or overextending the hip to prevent affecting venous return.

　　3. Protection of venous vessels, avoiding damage to the vascular wall:Especially for patients who have been on long-term intravenous infusion after surgery, try to protect their veins, especially the lower limb veins, to avoid repeated punctures at the same site in the same vein; when administering irritant drugs, try to avoid leakage of the drug outside the blood vessels.

　　4. Inhibition of platelet aggregation:Orally taking small doses of enteric-coated aspirin, compound Danshen tablets, etc., to reduce platelet aggregation.

　　1. Blood examination:Elevated white blood cell count; increased plasma lactate dehydrogenase; decreased levels of antithrombin III and plasminogen, which are both causes of renal vein thrombosis and the result of enhanced compensatory coagulation-fibrinolysis activity in the body after thrombosis. The levels of fibrinogen and plasma plasmin inhibitor α2-macroglobulin increase, and in the acute phase, they may also be low or normal due to consumption.

　　2. Urine examination:Significant increase in hematuria and urinary protein; acute decline in renal function is indicated by marked increase in blood urea nitrogen and creatinine.

　　3. Imaging examination:Non-invasive imaging examinations such as ultrasound, CT, magnetic resonance, and renal radionuclide scans are only diagnostic for renal vein trunk thrombosis, with typical signs being low-density thrombi visible in dilated renal veins, and the venous plexus around the diseased kidney showing a spider web-like collateral circulation, which has little diagnostic value for renal venous branch thrombosis.

　　4. Selective renal venography via percutaneous venous puncture:The diagnosis of renal vein thrombosis is of definitive significance, as it can clearly show the location, extent, and whether there is collateral circulation of the thrombosis, but due to the large blood flow in the kidneys, retrograde filling with contrast agent is somewhat difficult, and even false-positive results may occur. It is very important to master the depth of catheter insertion, the speed and total amount of contrast agent injection. Some clinical physicians also take the approach of injecting 10μg of adrenaline into the renal artery to reduce renal blood flow before performing renal venography, or using a renal venous balloon to transiently occlude renal blood flow during the contrast procedure to ensure that the contrast agent fully retrogradely reaches all renal venous branches, improving the contrast effect. Renal venography may cause serious complications, which should be prevented as much as possible. Firstly, the operation process may dislodge thrombi, causing pulmonary embolism; secondly, patients often have a hypercoagulable state, and damage to the vascular wall during the contrast process (such as at the puncture site) may lead to thrombosis, causing obstruction of the healthy renal vein or lower limb veins; thirdly, the damage to the kidneys caused by the contrast agent, the first two can be avoided through correct and careful operation, while the latter can be mitigated by drinking plenty of water or intravenous infusion to dilute the concentration of the contrast agent. In recent years, the non-ionic iodine contrast agent used is much less damaging to the kidneys than the commonly used ionic iodine contrast agent, but it is more expensive.

　　5. Histopathological examination:The pathological changes of the affected side of the kidney during renal vein thrombosis are an increase in organ volume, which may present as hemorrhagic infarction. In patients with nephrotic syndrome, renal biopsy during the acute phase can not only show the histological type of nephrotic syndrome but also show renal interstitial edema, renal glomerular capillary loop dilation and congestion, microthrombosis may occur, and sometimes multinucleated cells may adhere to the capillary wall. Long-term unresolved renal vein thrombosis can lead to tubular atrophy and renal interstitial fibrosis.

　　What foods should not be eaten for deep vein thrombosis:

　　1. Low-fat diet (forbidden to eat lard, egg yolk, and brain), and avoid spicy, sweet, and greasy foods.

　　2. Eat less or no animal fat and offal, such as lard, large intestines, and tripe, because these foods contain a high amount of cholesterol and saturated fatty acids, which are easy to worsen atherosclerosis.

　　3. Diet should be light, avoid salty food, and it is best not to eat pickled vegetables. Because eating too much salt can easily cause hypertension.

　　4. Avoid drinking stimulating beverages such as coffee and strong tea.

　　(The above content is for reference only, for details, please consult a doctor)

　　First, treatment

　　After the diagnosis of renal vein thrombosis, anticoagulation or thrombolytic therapy should be given as soon as possible to prevent thrombus spread, to dissolve thrombi, and to promote the recovery of venous return as soon as possible. For patients with acute thrombus formation, thrombolytic therapy may achieve significant effects, while for patients with chronic thrombus formation, long-term anticoagulation therapy can also prevent and reduce thrombus spread and the formation of new thrombi, thereby improving renal function and reducing complications.

　　1. Thrombolytic therapy:Thrombolytic therapy is to activate plasminogen, dissolve fibrin, and dissolve and dissipate thrombi. For patients with spontaneous thrombolysis after thrombus formation, it can also accelerate thrombus dissolution and prevent recurrence. Common thrombolytic agents include:

　　(1) Urokinase: The dosage is 200,000 to 400,000 U added to 100ml of 5% glucose solution, and it should be infused within half an hour. Maintain a continuous intravenous infusion of 100,000 U/h for 24 to 72 hours, then switch to heparin intravenous infusion, 2 times a day, for a total of 7 to 10 days.

　　(2) Streptokinase: It is used in the same way as urokinase, but there may be allergic reactions. Those who have never used streptokinase should undergo an allergy test first.

　　(3) Alteplase (tissue plasminogen activator, t-PA): It is a serine protease located in the vascular and tissue, as a natural thrombolytic plasminogen activator, it has a smaller impact on the systemic fibrinolysis system, may be safer and more effective than the former, but it is expensive and has not been popularized in clinical practice yet.

　　There is not much clinical experience with the thrombolytic therapy of renal vein by puncture and catheterization, as it is difficult to ensure the local drug concentration by intravenous catheter injection, so the exact effect needs further observation. There are reports that intrarenal arterial drug injection for renal vein thrombosis has achieved good results. Intrarenal drug administration may be more targeted than intravenous injection, and is worthy of further clinical verification and application.

　　2. Anticoagulation Therapy:For patients with chronic thrombosis or acute thromboembolism after thrombolytic therapy, it is necessary to give a longer period of intravenous anticoagulation therapy and long-term oral anticoagulation therapy. Commonly used drugs include:

　　(1) Heparin: Heparin acts on multiple links in the coagulation process, mainly by enhancing the activity of antithrombin III in plasma to inhibit thrombin and other coagulation factors, preventing the conversion of fibrinogen to fibrin, and inactivating the stabilizing factor of fibrin, thus hindering the formation of a stable blood clot. It can be used to prevent thrombosis and its spread, but has little effect on dissolving existing blood clots. It is mainly used for maintenance and consolidation treatment after thrombolytic therapy for acute arterial and venous thrombosis. The general dosage is 100U/kg, injected intravenously or subcutaneously once every 12 hours.

　　(2) Oral anticoagulants:

　　① Coumarin derivatives (such as warfarin), this class of drugs exerts anticoagulant effects by competing with vitamin K, causing the synthesis of coagulation factors dependent on vitamin K to be impaired. The dosage must be individualized, ranging from 2 to 15mg, and the prothrombin time must be monitored during the medication process. Vitamin K antagonists can be given in case of overdose.

　　② Low-dose aspirin or cilostazol (Lopid): This is an antiplatelet aggregation drug. For patients with thrombosis who cannot remove the cause, long-term anticoagulation therapy can choose the above oral preparations.

　　3. Surgical Treatment:The efficacy of surgical removal of thrombosis is not yet certain, and it is not currently considered a routine treatment in clinical practice. The clinical manifestations of renal intravascular thrombosis are generally not obvious, the damage to kidney function is not severe, and it is not a contraindication for surgery. In cases where acute renal vein trunk thrombosis leads to kidney failure and内科 treatment is ineffective, surgical treatment can be attempted to save life, but the risk may be relatively high.

　　II. Prognosis

　　The prognosis of renal vein thrombosis is closely related to the time of thrombosis formation and the time of treatment initiation. Early thrombolysis and anticoagulation therapy can reduce complications and alleviate kidney function damage. Those who fail to thrombolyze in time or whose thrombolysis is not successful may die of complications of renal failure and pulmonary embolism. Acute renal vein trunk thrombosis has a significant impact on kidney function and may have complications such as hypertensive crisis, with poor recent prognosis. Thrombosis formed slowly can be mitigated due to the formation of good collateral circulation, with a good prognosis.