Posterior nut-cracker syndrome: Urologist’s perspective – A mini review

Posterior Nut Cracker Syndrome (PCNS) is a rare clinical condition that occurs when the left renal vein gets compressed between the abdominal aorta and vertebral body. Posterior nutcracker phenomenon is a common anatomical abnormality, which is totally asymptomatic and diagnosed in a routinely performed abdominal imaging. The pressure gradient that develops between the renal vein and the inferior vena cava is the basic reason for all the features associated with this condition. Left renal venous entrapment would result in stagnation of blood in gonadal vessels that results in cascading effect resulting in a venous congestion and increased resistance to arterial blood flow in the kidney. Patients with pelvic congestion syndrome present with left loin pain and unilateral left varicocele. Gastrointestinal symptoms and arterial hypertension may also be the presenting symptoms. The symptoms depend upon the degree of pressure in renal veins and gonadal veins. When the dilated veins communicate with renal calyx, haematuria occurs. PNCS is best managed based on the severity of symptoms and the extent of clinical manifestations. Treatment options include conservative treatment, intra-vascular stents, chemical cauterisation, open surgical intervention and finally if everything fails, nephrectomy. PCNS is a rare entity that affects mostly females and can present with a variety of signs and symptoms. A high index of clinical suspicion is needed to achieve a prompt diagnosis. Conservative treatment is recommended for patients with mild symptoms. Severely symptomatic patients might benefit from


INTRODUCTION
utcracker syndrome is a clinical manifestation of a prolonged pressure over the left renal vein (LRV; 1). Mechanical compression of LRV between aorta and superior mesenteric artery is Anterior Nutcracker syndrome (ANCS) and that between the abdominal aorta and vertebral body is posterior Nutcracker syndrome (PNCS; 2,3). The term ANCS is a relatively common condition which is more often considered synonymous with NCS. While it is a common observation that the ANCS could result in left sided varicocele, the PNCS needs more detailed description, as the Retro-aortic left renal vein (RLRV) causing venous compression would be of more relevance to the urologist and often gets missed out during evaluation.

Pathophysiology
PNCS occurs when the left renal vein gets compressed between the abdominal aorta and vertebral body (4,5). Due to this mechanical compression on LRV, a reno caval pressure gradient is created which is the fundamental reason for all symptoms associated with PNCS (6). Stasis of blood in the gonadal veins leads to heaviness or discomfort in loin, that may delay the diagnosis (7). As PNCS is often under-reported, its clinical manifestations mimic and are often mistaken as presentations of other more common illnesses (8). LRV compression between the aorta and vertebral body would result in a rise in the venous pressure in the distal venous portion. This would cause a decrease in flow and also a temporary retention of venous blood. This will initiate a cascading effect resulting in a venous congestion, increased resistance to arterial blood flow in the kidney, leading onto a collateral blood flow. The collateral blood flow would act as a 'pop off' mechanism, resulting in a reduction in the arterial resistance and increase in renal perfusion. An upright erect posture further worsens the angulations, leading on to an exacerbated hemodynamic response, which are responsible for the various clinical manifestations (9).
It is important to differentiate Posterior nutcracker syndrome (PCNS) from Nutcracker Phenomenon (10). This phenomenon is a common anatomical abnormality, which is totally asymptomatic and diagnosed in a routinely performed abdominal imaging. On the other hand, PCNS includes a variety of typical or atypical symptoms that the patient could present with.

Why is it important for urologists?
Loin pain and haematuria have always been perplexing problems for the urologists since time immemorial. Most patients with PNCS present with vague loin pain or upper abdominal discomfort. In the absence of overt haematuria, most of such patients rarely present themselves to urologists. Presence of either micro or macroscopic haematuria N adds to the confusion for the primary care physicians or nephrologists, where there is a common tendency to make a diagnosis of glomerulonephritis.
Clinical Pathologists have tiresomely examined renal biopsy specimens to identify the probable cause for recurrent unexplained gross haematuria associated with loin pain. Various authors have described renal cysts, angiomas, microhaemangiomas, vascular anomalies, and renal veno-calyceal fistulae in the renal fornices as potential causes for this condition (11). Lack of specific clinical findings necessitates a higher suspicion for the diagnosis of PNCS. Noninvasive CT angiogram may be needed to confirm PNCS (12). On many occasions, patients with Posterior nut cracker syndrome present with vague epigastric discomfort, dyspepsia, vomiting, left loin pain and micro haematuria. The presence of such atypical symptoms may prompt the patients to consult a physician, causing further delay in making a proper diagnosis. The purpose of this manuscript is to highlight to the clinicians and urologists the rarity of such a condition and also to highlight the myriad of urological symptoms that the PNCS can present with, so that an early diagnosis is made and treated appropriately.

Classification
Hoeltl et al., had classified the RLRV into 2 distinct types: Type 1 is associated with an obliterated ventral preaortic limb of the LRV, but persistent dorsal retroaortic limb which subsequently joins the IVC in the orthotopic position. On the other hand, obliteration of ventral limb of LRV can produce Type 2 anomaly. Jong et al in 2010 subsequently reported the congenital anomalies of the RLRV as four types. Type 3 anomaly is the circumaortic LRV. One vein passes posterior and the other vein passes anterior to the aorta to join the IVC. In Type 4 anomaly, the ventral preaortic limb of the LRV is obliterated, and the remaining dorsal limb becomes the RLRV and joins the left common iliac vein (13). Though Posterior nut cracker syndrome by definition can be seen in all 4 types, it is classically seen in Type 1 anomaly. Fig 1 describes the schematic illustration of the types of RLRV (13).

Epidemiological characteristics
The development of inferior venacava by itself is such a complex process that efforts to make the understanding of development of renal vein make it even more complicated. Left renal vein entrapment, also known as Nut cracker syndrome, was first described by El-Sadr and Mina in 1950 (14). However, the term Nut cracker Syndrome was first used by Chait et al., (15), though the Belgian physician De Schepper is the one, who was first credited with this terminology in 1972 (16).The overall incidence of RLRV was reported as 3% and a vast majority of them are asymptomatic (17).

Demographic characteristics
Most of the patients remain asymptomatic throughout their lifetime. While most patients remain healthy, many of the symptomatic ones develop clinical manifestations during their second or third decade of life (18). It usually affects women more than men and in most cases present in the 3 rd or 4 th decades of life (19). Some patients show only microscopic haematuria, which may be picked up during routine evaluation. Rudloff observed a second peak to occur in middle aged women, who might present with symptoms resulting from pelvic venous congestion due to massive reflux of blood in gonadal vein and pelvic varices (20). Although anecdotal reports of NCS affecting the siblings have been reported, NCP is not established to have a hereditary transmission (21). Various pathophysiological changes that happen during puberty, including a sudden spurt in the body height, angulation that develops between the vertebral body and aorta and a low body mass index are also considered to be the reasons for NCS (22).

Clinical characteristics
Other patients may present with left loin pain with unilateral left varicocele due to venous stasis at gonadal vessel, also known as Pelvic congestion syndrome. Gastrointestinal symptoms and arterial hypertension may occasionally be the presenting symptoms (23). The severity of symptoms varies depending on the renal venous pressure, engorgement of gonadal veins, left suprarenal vein and ascending lumbar veins (24). Haematuria may be the result of communication between dilated venous sinuses and adjacent renal calices.
Microhaematuria in PCNS, though rare, is not so uncommon, if specifically looked for. The mechanical compression of the LRV between the aorta and the vertebral body results in a rise in pressure gradient between the LRV and the vena cava. This rise in pressure gradient, in turn leads to the rupture of the membranous barrier between the smaller veins and the collecting system in the renal fornix, resulting in micro haematuria (25,26). Ahmed also considered a pressure gradient of 3 mm Hg or more as indicative of renal hypertension. Though this was a study done on patients with Anterior Nut cracker syndrome, Lopatkin postulated that haematuria may be the result of communication between dilated venous sinuses and adjacent renal calices and observed in patients with PNCS also (27). However pressure gradients have been reported to vary with position and hydration, as well as the degree of collateralization. Daily et al had reported a direct correlation between the left renal vein pressure (LRVP) and the degree of haematuria (28). However, Park et al, in their systematic review on PCNS, had found no such direct correlation and observed that patients with lower LRVP of 4.4 mm Hg manifested with macro haematuria while patients with higher LRVP of 8 mm Hg showed only a microhaematuria (29,30).

Treatment
Patients with PNCS are best managed based on their symptomatology, the clinical manifestations, severity of LRVP and hypertension. The various treatment options available include Conservative treatment, intra-vascular stents, chemical cauterisation, open surgical intervention and finally if everything fails, nephrectomy.
In patients with mild haematuria and in young individuals, who are willing to come for a regular follow up, conservative and supportive treatment is offered. Young adults, aged less than 18 years can be followed up for a minimum period of 2 years as there is a 75% chance that there may be a complete resolution of microhaematuria (31). Endovascular stenting is a viable option for patients who have bothersome pain and hypertension due to elevated LRVP (32). However, its future role in the management of this condition remains to be established and the potential complications like Fibromuscular dysplasia, stent migration, thrombosis, restenosis and embolization have to be borne in mind (33).
Few anecdotal reports on Intra Pelvic Chemical Cauterization using 0.1% Silver nitrate through ureteric catheter placement are available in literature (34). Gong et al observed that gross haematuria improved with intra pelvic instillation and the patient remained symptom free for the next 16 months follow up. However, more case series and metaanalysis are needed to validate this claim. Open/Laparoscopic surgical procedures include left renal vein transposition andrenal auto-transplantation (35,36,37). In intractable cases, when all conservative treatment fails or when haematuria persists even after transposition of left renal vein, nephrectomy is recommended as a palliative measure (38).

CONCLUSION
Posterior Nutcracker Syndrome due to the compression noted in the Retro aortic renal vein is a rare entity that affects mostly females and can present with a variety of signs and symptoms. This review article reinforces the need for a high index of clinical suspicion in order to achieve a correct and prompt diagnosis. Conservative treatment is recommended for patients with mild symptoms. Patients with serious impairment or severe symptoms may benefit from a surgical or endovascular intervention.

ACKNOWLEDGEMENT
The authors profusely thank Professor LEE SANG DON M.D., PhD, for permitting us to reproduce the Fig. 1

CONFLICTS OF INTEREST
Authors declare no conflicts of interest.