Nutcracker syndrome, also known as left renal entrapment syndrome, is a clinical phenomenon caused by compression of the left renal vein (LRV) traveling through the superior mesenteric artery (SMA) at an angle between the abdominal aorta and the superior mesenteric artery. It is a clinical phenomenon caused by the compression of the left renal vein (LRV) when it travels through the angle between the abdominal aorta and the superior mesenteric artery (SMA), often manifesting as hematuria or proteinuria, lumbar and abdominal pain and varicocele.
1.Etiology
Anatomically, the inferior vena cava (IVC) and the abdominal aorta run parallel on both sides of the retroperitoneal spine, the former on the right and the latter on the left. The superior mesenteric artery (SMA) is located anterior to the abdominal aorta and forms an angle with it. The right renal vein is directly injected into the IVC, whereas the left renal vein (LRV) is injected into the IVC by crossing the angle formed by the SMA and the abdominal aorta, which is 45 O to 90 O. Normally, the angle is filled with mesenteric fat, lymph nodes and peritoneum so that the LRV is not compressed. However, when the height of adolescence grows rapidly, the vertebral body is overstretched, and the body shape changes dramatically, this angle becomes smaller, so that the LRV is compressed, causing left renal vein hypertension, which is called “anterior” left renal vein compression syndrome. 98% of normal people have IVC and LRV pressure gradient <0.13kpa (0.973mmHg). The pressure gradient was ≥0.40kpa (3mmHg) in the left renal vein compression syndrome. Another rare left renal vein compression syndrome has also been reported in the literature, in which the left renal vein does not cross between the abdominal aorta and superior mesenteric artery, but passes posteriorly from the abdominal aorta into the inferior vena cava and develops left renal vein hypertension due to compression by the abdominal aorta, hence the term "posterior" left renal vein compression syndrome.
2.Pathology
Renal venous hypertension after compression of the left renal vein is the main cause of hematuria. The compression of the left renal vein causes blood stasis in the kidney and its surrounding veins, and the stagnant venous blood eventually causes the thin-walled veins of the renal calyces to rupture and bleed, and blood enters the collecting system and the fornix of the renal calyces, resulting in hematuria. At the same time, the left testicular vein, left ovarian vein and part of the pelvic vein are blocked and bruised due to the obstruction of reflux. Renal vein bruising can also affect the blood supply of the renal interstitium, leading to the decrease of renal tubular reabsorption function, resulting in the increase of α1 microglobulin in urine and proteinuria.
3.Clinical manifestations
It occurs in males from adolescence to 40 years old, and in children aged 4-7 years old, with a high prevalence in 13-16 years old, male:female=24:5. The main manifestations are episodes of asymptomatic hematuria and proteinuria. The hematuria may present as microscopic hematuria or may appear as carnal hematuria after strenuous exercise or cold. There may be left-sided abdominal pain and lumbago and back pain, dizziness and weakness. Varicocele in men, dysmenorrhea in women, irregular menstrual bleeding, and sexual dysfunction in adult men, called genital vein syndrome (due to stasis in the testicular or ovarian veins that drain into the LRV), thus the possibility of left renal vein compression should be thought of in patients with chronic pelvic inflammatory disease caused by pelvic vein stasis. Chronic fatigue syndrome may be present in some children. Occasionally, benign duodenal stasis occurs in association with duodenal compression (SMAS). Pregnancy may worsen the symptoms. The clinical manifestations of this disease lack specificity and are easily confused with IgA nephropathy, thin basement membrane disease and Alport syndrome, etc. There are many clinical misdiagnoses.
4.Diagnosis
4.1 Ancillary tests
4.1.1 Laboratory tests
Hematuria or/and proteinuria with increased α1 microglobulin in urine is seen on urine microscopy. If a single kidney urine sample is done, it is more significant for diagnosis, but it should be noted that ureteral cannulation itself can also cause microscopic hematuria.
4.1.2 Color Doppler ultrasonography
Measure the internal diameter of the left renal vein (at the point of compression) crossing the angle between the abdominal aorta and the superior mesenteric artery (a) and the internal diameter of the left renal vein near the hilum (b), and then measure the blood flow velocity at these two points with pulsed wave Doppler. These parameters were measured again in the standing position after the subject had been standing for 15 minutes. The ratio of the internal diameter of the left renal vein at the widest and narrowest points (b/a), and the ratio of the blood flow velocity at the compression point (Va) and near the renal portal (Vb) were calculated. Ultrasound diagnosis is based on: (i) the flow velocity (Va) of the left renal vein (at the compression site) is significantly increased in the lying position, and even more significantly in 15 minutes of standing, with flow velocity > 100 cm/s; (ii) the ratio of the inner diameter of the widest and narrowest left renal vein is > 3 in the lying position, and > 5 after 15 minutes of standing. the sensitivity and specificity of ultrasound examination for left renal vein compression syndrome are 78% and 100%, respectively, and it is the first choice for this disease.
4.1.3 Magnetic resonance angiography (MRA)
Its three-dimensional imaging technique allows visualization of left renal vein compression. The relationship between the abdominal aorta, superior mesenteric artery and left renal vein is observed, the cross-section of the left renal vein stenosis site, and the degree of the angle between the abdominal aorta and superior mesenteric artery is measured. The angle between the abdominal aorta and the SMA is normally 450-900, but it is diagnostic when the angle is less than 350. MRA is not suitable for metallic foreign bodies and pacemaker or defibrillator implants in the body.
4.1.4 Spiral CT angiography (CTA)
Its findings and significance are the same as those of MRA. With the rapid development of multi-layer spiral CT technology, it can even surpass MRA in terms of clarity of vascular imaging, but CTA requires the application of iodine-containing contrast agent, and its nephrotoxicity should be considered in patients with proteinuria and abnormal renal function who have not yet excluded organic renal pathology.
4.1.5 Left renal vein angiography (DSA)
Renal venography can directly observe the compression of the left renal vein and the presence of dilated, tortuous and refluxed collateral circulation around the left renal vein, but a negative renal angiographic result cannot exclude the diagnosis, because the contrast agent injection can cause changes in its local blood flow status. The pressure difference between the inferior vena cava and the left renal vein can also be measured during imaging, which is < 1 mmHg in normal subjects and significantly increased to more than 3 mmHg in left renal vein compression syndrome.
4.2 Clinical diagnostic ideas and diagnostic criteria
Patients with hematuria and proteinuria should think of the possibility of left renal vein compression, especially in children, after excluding tumors, infections, stones and acute and chronic nephritis. It should also be considered in patients with chronic pelvic inflammatory disease caused by pelvic vein stasis and left spermatic varicose veins. The diagnosis must be confirmed by laboratory tests and special examinations.
Clinical diagnostic criteria: ①clinical exclusion of hypercalciuria, tumors, stones, infections, malformations and glomerular diseases; ②non-glomerular urine red blood cell morphology, morphologically normal >90%; ③an ultrasound diagnosis meeting these two criteria: proximal flow velocity (Va) of the left renal vein is significantly increased in the prostrate position, and the increase is more obvious in 15 minutes of standing, with flow velocity > 100 cm/s; the internal diameter of the widest and narrowest part of the left renal vein in the prostrate position is The ratio of the widest and narrowest internal diameter of the left renal vein is >3 in the lying position and >5 after 15 minutes of standing; ④ The angle between the superior mesenteric artery and the abdominal aorta is <350 by MRA or CTA. The diagnosis can be confirmed by meeting these four criteria.
5.Treatment
5.1 Indications for selection of treatment
The disease is a renal hemodynamic alteration, mostly benign, and the prognosis can be. Whatever surgical treatment is used, it is invasive, and complications and uncertainty of the treatment effect occur, so it should be chosen carefully. In minors (≤18 years), conservative treatment is generally recommended after diagnosis. If symptoms do not resolve or worsen after more than 1 year of medical treatment; complications such as weakness, anemia, lumbar and rib pain and varicocele or the development of renal impairment, surgical treatment may be considered. For adults (>18 years old), surgical treatment is feasible for those whose symptoms and signs do not improve with medical treatment after diagnosis.
5.2 Internal treatment
The main treatment is symptomatic management and close follow-up. In some children, as the angle between the superior mesenteric artery and the abdominal aorta increases with age, the angle of fat and connective tissue increases as well as the establishment of collateral circulation around the left renal vein, which improves the state of renal venous stasis and relieves the symptoms.
Therefore, for children and patients with left renal vein compression syndrome with a short course and mild symptoms, conservative medical treatment is recommended, and further treatment will be decided according to changes in the condition.
5.3 Surgical treatment
5.3.1 Surgical treatment
A variety of different surgical procedures have been used with the aim of relieving left renal vein compression, and there is no uniform surgical procedure for this condition.
Surgical options.
(1) Superior mesenteric artery dissection and reimplantation The superior mesenteric artery is dissected at the proximal root and the distal end is moved down below the renal artery to perform a terminal anastomosis with the aorta. After completion of the anastomosis, the fibrous connective tissue around the stenotic segment of the renal vein needs to be further released so that the compressed segment of the renal vein can be fully dilated. Some authors also free the superior mesenteric artery and then perform external suspension fixation
(2) Left renal vein inferior displacement – inferior vena cava telangiectomy The left renal vein is dissected at the point of confluence with the inferior vena cava, and the left renal vein is fully freed, then the left renal vein is inferiorly displaced by 5 cm, and then a telangiectomy is performed with the inferior vena cava.
(3) Spermatic vein (ovarian vein)-inferior vena cava anastomosis is mainly used for left renal vein compression with pelvic varicose vein, and 60% of the patients’ symptoms are improved after the operation.
(4) Autologous kidney transplantation, etc. The left kidney is directly transplanted into the autologous left or right iliac fossa after resection.
(5) Left renal vein inferior vena cava autologous saphenous vein bypass transfer Some authors have also used artificial vessels instead of autologous saphenous vein for bypass transfer.
(6) Extracorporeal support with a ring The extracorporeal support technique uses a ringed PTFE artificial vessel, which was first reported to be performed under an open abdomen by loosening the left renal vein and then wrapping the ringed artificial vessel around the left renal vein. The length of the ringed artificial vessel is usually based on the distance from the left adrenal vein or left gonadal vein to the inferior vena cava. This procedure can also be performed laparoscopically to minimize trauma. It is generally considered to be used when the patient is not suitable for long-term anticoagulation and cannot be endoprosthetically stented.
5.3.2 Endovascular treatment
Left renal vein stenting: After local anesthesia, the femoral vein is punctured, a vascular sheath is placed under DSA surveillance, the catheter is inserted distal to the LRV, and the stent is delivered into the narrowest part of the LRV after imaging and manometry, and the stent is released, with the distal end not exceeding the opening of the left gonadal vein and the proximal end not exceeding the confluence of the LRV and the IVC. The stent is generally not pre-dilated with a balloon prior to self-expanding stent implantation. The size of the stent is usually chosen as 4 cm in length; too short is not easy to locate the stenosis and too long may cover the opening of the genital vein; the diameter of the stent is based on the diameter of the widest part of the left renal vein measured by ultrasound, MRA or CTA plus 20%.
Postoperative anticoagulation therapy was routinely applied. Due to the high renal blood flow and the fact that endothelial cells can cover the stent about two months after stent implantation, there is less chance of thrombosis, and oral anticoagulants are usually required for 2 months after surgery.
5.3.3 Retrograde pelvic perfusion therapy with pantoglucosamine
The cystoscope is used to insert a catheter into the left ureter, and pantoproglutamine is instilled under pressure into the renal pelvis, creating hypertonicity for a short time, resulting in aseptic inflammation of the abnormal traffic LRV and surrounding tissues, edema, adhesions, stenosis, and occlusion of the canal wall, thus achieving therapeutic goals. Some authors have also used 1% silver nitrate solution for retrograde renal pelvis perfusion therapy.
Among the 83 patients with Nutcracker syndrome who were admitted to our hospital and treated surgically since October 1998, 3 cases were treated with superior mesenteric artery transposition, 2 cases were treated with left renal vein transposition, 75 cases were treated with left renal vein endovenous stenting, and 3 cases were treated with retrograde pelvic perfusion with pantethidine.
Objective evaluation between the various procedures is difficult due to the lack of long-term follow-up of large numbers of cases. The superior mesenteric artery dissection and reimplantation can avoid left renal vein thrombosis and renal ischemia, but requires superior mesenteric artery anastomosis, which has the disadvantage of potentially endangering intestinal blood flow; left renal vein inferior displacement – inferior vena cava terminal anastomosis has a short renal ischemia time, but has the possibility of renal vein thrombosis after surgery; autologous kidney transplantation requires two surgical incisions, requires arterial anastomosis, has a long renal ischemia time and The disadvantages of autologous kidney transplantation include two surgical incisions, arterial anastomosis, long renal ischemia time and complications. Extracorporeal ringed artificial vessel support requires open abdomen and placement of the ringed artificial vessel, which can stimulate left renal vein thrombosis after surgery. Regardless of the surgical treatment, it should be noted that the left renal vein stenosis is not solely caused by the compression of the superior mesenteric artery, but the thickened fibrous connective tissue at the root of the superior mesenteric artery also tightly binds the left renal vein, and severing the superior mesenteric artery alone cannot completely relieve the compression, and the fibrous connective tissue here must be completely disconnected.
Percutaneous left renal vein stenting is less invasive and more effective in correcting LRV hypertension, but the risk of post-stenting migration, restenosis and thrombosis has always been a concern. Through years of treatment practice, we have learned that with the recent advances in interventional device technology, especially the improvement of self-expanding stents in terms of flexibility and radial support, stent implantation failure or postoperative migration can be avoided as long as the stent diameter is correctly selected and the operator’s operating technique is excellent. In our case, one postoperative stent displacement, one implantation failure, and one poor stent positioning occurred at an early stage and were related to the stiffness of the stent used at that time, the small diameter selected, and the poor interventional technique. As for the problem of postoperative thrombosis, there was no case of thrombosis in our case probably because of the high renal blood flow and the ability of endothelial cells to cover the stent about two months after stent implantation. In comparison, we believe that percutaneous left renal vein stenting is minimally invasive, effective, and can immediately correct LRV hypertension, and should be the method of choice for the treatment of Nutcracker syndrome.
Whether surgical or interventional, postoperative LRV pressure is significantly reduced, but individual patients may still have hematuria. The reason for this is that there is an established abnormal traffic LRV formation between the venous system and the urine collection system; therefore, patients should be made to fully understand this possibility preoperatively. In contrast, retrograde renal pelvic perfusion with pantoglucosamine or 1% silver nitrate solution has the advantages of ease of operation, safety, good recent efficacy, and few adverse effects. However, because this method fails to relieve the left renal vein hypertension, and the silver nitrate solution is corrosive and painful, improper treatment can cause kidney, ureteral and bladder burns and serious hemolytic reactions, and the long-term efficacy needs further observation. However, if this method is used in patients who still have hematuria after surgery or interventional treatment may have good synergistic effect.