Nutcracker syndrome (NCS) is a rare condition characterized by a constellation of symptoms and clinical findings resulting from extrinsic compression of the renal vein. The most common form of NCS results from entrapment of the left renal vein (LRV) between the aorta and superior mesenteric artery (SMA). Although considered a rare disorder, NCS should be in the differential diagnosis of patients that present with intermittent hematuria, debilitating flank pain, pelvic discomfort because of venous congestion, orthostatic proteinuria and varicocele formation in men. The diagnosis can be challenging because of substantial variation in symptomatology and presence of ‘nutcracker anatomy’ in individuals who lack signs or symptoms of NCS. The anatomic configuration attributed to NCS may represent — in some patients — a normal variant, and symptoms may be accounted for by other conditions, making NCS a diagnosis of exclusion often reached after a protracted process of elimination. In addition, diagnostic tests are not always conclusive. These factors help explain why patients are often diagnosed late, experiencing pain that significantly impacts quality of life.
In patients with symptoms suggestive of NCS, a renal Doppler ultrasound is typically the initial imaging investigation, providing a noninvasive way of defining the anatomy and calculating velocities at different levels of the renal vein. Axial imaging via contrast-enhanced computed tomography (CT) or MRI are second line imaging modalities that provide further anatomic detail, including the presence of collaterals (which can be of value when planning a by-pass). Despite the increasing role of CT and MRI in the diagnosis of NCS, a standardized diagnostic criterion remains elusive. A retrospective review involving 324 CT scans of asymptomatic renal donors showed that up to 30% of patients satisfy at least one of the radiologic variables of interest in NCS evaluation. Thus, we propose a stepwise, multimodal approach in the diagnostic evaluation of NCS. This algorithm follows the tenet of ordering investigations from least to most invasive until either a diagnosis is established or the exclusion of NCS is made. When ultrasound and axial imaging remain inconclusive, phlebography can be considered. This study provides great anatomical definition, shows the presence of collaterals and flow to the gonadal vessels, and is highly suggestive of NCS if the renal vein-cava pressure difference is more than 3 mmHg.
In addition to findings on imaging studies, it is sometimes difficult to ascertain if the symptoms are truly related to NCS. An exciting contemporary approach, the University of Wisconsin-Loin Pain Hematuria Syndrome (UW-LPHS) test, may play a role in making this distinction. The UW-LPHS test involves endoscopic retrograde installation of 0.5% bupivacaine solution to the affected renal collecting system and ureter. The solution stays within the collecting system for 5–10 min, retained with a ureteral catheter before being drained. Patients experiencing postprocedure symptom relief with the UW-LPHS test have been shown to have a positive response to renal auto-transplantation, which is one of the most invasive and definitive management options.
The treatment of NCS can be broadly grouped into conservative, endovascular, and operative management. In a retrospective review involving 21 pediatric patients diagnosed with NCS (mean age of 11.7 years, mean follow-up 52 months), 16 patients had symptom resolution without the need for intervention. In pediatric and adolescent patients, conservative management should be the first line option, with careful consideration of patient symptomatology and preference. When treatment is warranted, LRV stenting is one of the minimally invasive options. Avgerinos et al. published their outcomes showing a 2-year patency rate of 85.2% and partial or complete symptom resolution in 13 of 18 patients. There are some reservations with the use of this strategy, including unknown long-term issues with having a stent in the venous system in close proximity to the aorta and SMA. Moreover, it is unclear if there are any considerations when applied to a patient that is not fully developed, or the implications with future pregnancies. Other minimally invasive options include laparoscopic-assisted or robotic surgery. A case-series involving six patients who underwent robotic-assisted extravascular stent placement showed resolution of symptoms, minimal blood loss, and a median hospital stay of 1.5 days. Vein transposition techniques, previously performed via an open approach, can also be done laparoscopically or robotically. Lastly, auto-transplantation and nephrectomy remain options for patients with refractory symptoms. In patients who elect to have a nephrectomy, organ donation to a patient in need of renal replacement therapy is a consideration.
To date, there is no head-to-head comparison available between the different interventions available. Therefore, it is our belief that the treatment approach for NCS should be tailored for each individual and in a multidisciplinary setting. In a recent patient with NCS in a solitary kidney at our institution, we performed an in-situ gonadal vein valvulotomy and side-to-side gonado-iliac bypass. This treatment plan considered factors, such as potential disruption to renal perfusion in the setting of a solitary kidney, patient age and potential need for long-term anticoagulation, as well as native anatomy and venous collateralization. This novel management technique involved colleagues from interventional radiology and cardiovascular surgery. Other contemporary treatments involve regional anesthesia, including a case report that outlined the benefit of serial ganglion impar blocks in a patient with refractory NCS. These treatment options support the importance of a step-wise, multidisciplinary and innovative strategy in the management of this complex condition.
Despite the improvement and increased availability of diagnostic and treatment modalities, a standardized diagnostic approach and treatment remains elusive for patients with NCS. Herein we propose an algorithm that broadly describes the pathway we follow in individualizing the evaluation and management of NCS.