Clinical importance of anatomical variations of renal vasculature during laparoscopic donor nephrectomy

Introduction Laparoscopic live donor nephrectomy has become a well-accepted practice in most transplant units. However, the variations and complex of renal vasculature may make the surgery even more challenging during laparoscopic donor nephrectomy. The aims of this article are to review embryology of the renal vasculature development and the clinical significance of renal vascula - ture anomalies during


Introduction
Laparoscopic donor nephrectomy has become the standard of care in most transplant centres around the world. It is a unique surgery to predispose the surgeons under stress as healthy donors have a major surgery purely for others' benefits rather than themselves. Renal vessels are known with a wide range of variations that have also been evidenced during live kidney donor work-up in recent years. Most of these variations may otherwise have no clinical significance other than the surgery for laparoscopic donor nephrectomy. These variations can lead to significant surgical complications or even lifethreatening events if unrecognised. There are increased reports in the literature identifying variation of renal vasculature during live donor nephrectomy [1][2][3][4][5][6][7][8][9][10][11] . Undoubtedly, a thorough knowledge in understanding of the embryologic development and associated anatomy of renal vessel variations will equip the surgeons to anticipate and manage these potential risks successfully to prevent the complications. Therefore, the aims of this review are to explore the embryology of renal vasculature and associated variations and to emphasise the importance during laparoscopic live donor nephrectomy.

Discussion
The authors have referenced some of their own studies in this review. These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964), and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in these studies.

Embryology of renal arteries
The kidneys ascend to the lumbar region below the adrenal glands during the embryological development between the sixth and ninth weeks possibly due to differential growth of the lumbar and sacral regions of the embryo. As the kidneys ascend they are vascularised by a succession of transient aortic sprouts that arise at higher levels progressively. These arteries do not elongate to follow the ascending kidneys; instead they are degenerated and replaced by successive new arteries. The final pair of arteries forms in the upper lumbar region as the definitive renal arteries. Sometimes, the inferior pair of arteries is not degenerated and becomes an accessory lower pole artery. The kidney may become ectopic in the pelvis if it fails to ascend adequately ( Figure 1) The horseshoe kidney may be developed if the lower pole is fused and becomes trapped by the inferior mesenteric artery and thus the kidney cannot ascend to the lumbar region 12 .
The origin of intrarenal vasculature has not yet been completely understood. It was postulated that the renal vasculature derived exclusively from the branches off the aorta and other pre-existing extrarenal vessels. However, there was evidence that the renal vessels may originate within the embryonic kidney from *Corresponding author Email: bulang.he@health.wa.gov.au the vascular progenitor cells 13,14 . It was also thought that both vasculogenesis and angiogenesis may play a role in the development of renal vasculature 12,15 .

Renal artery variations
In the context of live donor work-up on computed tomography angiogram (CTA), the single normal renal artery is about 70%, two renal arteries 25% and three renal arteries 2.6% [16][17][18] . The prevalence of multiple renal arteries on both sides is about 12% 19 . Rarely, four renal arteries on each side may be encountered during imaging work-up of 1.3% 16,19,20 . The most common variations of renal artery are excess renal arteries and early bifurcation. The accessory renal artery is defined as the artery that has a separate aortic ostium from the main renal artery and supply to the upper or lower pole. The aberrant renal artery is defined as the artery that has a separate aortic origin but goes into the renal hilum. The incidence of excess renal arteries ranges from 25% to 40% 17,21,22 . In addition, the renal artery can arise at unusual aortic origin such as above the superior mesentery artery or celiac trunk, in which the renal artery may be entrapped in the medial arcuate ligament 5,16,23 . In this situation, the renal artery may be compressed and presented with symptoms of hypertension. The compression to renal artery may occur in the presence of low insertion of median arcuate ligament or high origin of the renal artery 24 (Figure 2a, 2b). As such, the donor nephrectomy should be considered on this side. The inferior renal accessory artery can arise from the iliac artery or as a common trunk with the inferior mesenteric artery 25 . The right aberrant renal artery may be precaval 23 . The accessory renal artery can rarely arise from the mesenteric artery or lumbar arteries 19 . In addition, the main arterial supply of a kidney may be from an extension of the opposite renal artery 26 .
Laparoscopic donor nephrectomy can be safely performed in the donor with multiple renal arteries with equivalent transplant results to those kidney grafts with a single renal artery [27][28][29] . The technique for reconstruction of multiple renal arteries has also been established with satisfactory results [29][30][31] . It is essential to interpret CTA accurately prior to surgery and identify the excess renal artery during surgical dissection.
The early branching of renal artery is defined as the branches arising within 15 mm from the origin of the main renal artery ostium 18 . The incidence is around 10%-12% 16,17,32 . In author's experience, the one ostium usually can be obtained during laparoscopic donor nephrectomy if the early branches are beyond 10 mm from the origin of the main renal artery. Otherwise, the renal arteries can be reconstructed on the back table or separate renal artery anastomosis to the recipient can be performed successfully 30,31 . Review posterior abdominal wall, need to be dissected and divided carefully to expose the proximal part of the renal artery for a better length, in particular if there are early renal artery branches. Lumbar vein is usually short in length and big in calibre. It can become a challenge during laparoscopic donor nephrectomy because of the risk of accidental injury and subsequent bleeding, which may lead to conversion to open surgery [39][40][41] . Therefore, the injury to lumbar veins should be ultimately avoided. In addition, the anomalies of lumbar vein are frequently encountered during left side donor nephrectomy including agenesis and collaterals 1 . Often, there are one or two lumbar veins, accounting for 65%-80%. Rarely, there are three lumbar veins of 3% 1,42 . The multiple lumbar veins may make up a net-like structure (Figure 3). The lumbar veins were usually inferior to the renal vein and inferior and posterior to the renal artery, usually at the lumbar vertebral level-1. They may not be adequately visualised during surgery by transperitoneal approach, in which the injury of lumbar vein is likely to cause serious bleeding 43 . Therefore, the retroperitoneal approach offers a better view to identify the details of lumbar vein more

Embryology of the renal veins
The formation of the renal vein is a complex process during embryologic development. In brief, the initial venous drainage in the embryo is by anterior paired cardinal veins draining the cranial half of the body and by posterior paired cardinal veins draining the caudal half of the body 33  The subcardinal veins extend caudally forming the gonadal vessels 33 . Based on the complex of venous development during gestation, it is therefore understood that renal vein anomalies are closely associated with malformation of IVC 34 .

Multiple renal veins and lumbar veins
Clinically, conventional single renal vein is the most common anatomy in live donor work-up, but anatomy variations are identified in 5%-30% 16,19,35 . The most common renal venous anomaly is the occurrence of dual renal veins, accounting for 15%-30%, frequently on the right side 18,19,23,36 . In this case, the smaller tributary can often be ligated without significant consequence, whereas the larger vein should be preserved to maintain better venous drainage 37 . Anomalous veins are likely to be dilated and tortuous predisposing injury to occur during surgical dissection 38 . In addition, the lumbar veins, which are the veins communicating the left renal vein and the left ascending lumbar vein running along the inside of the   33,45 . The prevalence of left-sided IVC is from 0.1% to 0.4%, and double IVC ranges from 0.3% to 0.7% 9,16 . These anomalies were mostly incidental findings on the images or during surgery. However, these should not be contraindicated for live donor nephrectomy. There are some reports of successful laparoscopic donor nephrectomy with duplicate IVC or left-sided IVC and subsequent successful kidney transplant [46][47][48][49] . The left-sided IVC should be preserved rather than sacrificed during nephrectomy due to the risk of ipsilateral oedema in the pelvis and leg 50 . In addition, the left-sided IVC and duplicated IVC may increase the risk of thromboembolism due to the increased blood flow stasis. These anomalies may also complicate the management of deep vein thrombosis when consideration of filter insertion is decided 51 . If one IVC is missed, then recurrence of pulmonary embolism may occur 51,52 .

Circumaortic renal vein and retroaortic renal vein Circumaortic renal vein
The persistence of the intersupracardinal anastomosis and left subsupracardinal anastomosis and left dorsal renal vein gives rise to circumaortic renal vein with two left renal veins 53 . The incidence ranges from 8% to 17% during live kidney donor workup 18,36 .

Retroaortic renal vein
It develops due to the persistence of the left subsupracardinal anastomosis, the intersupracardinal anasto-mosis and the dorsal left renal vein, with degeneration of ventral renal vein. 38 It is classified as two types: type 1 is developed as a result of persistence of the left subsupracardinal anastomosis, the intersupracardinal anastomosis and the dorsal left renal vein and type 2 is formed due to the persistence of the left subsupracardinal anastomosis and left supracardinal vein 54 . Retroaortic renal vein ranges from 3% to 4.7% on CTA during live donor work-up 18,36,55 (Figure 4a-c) while it was reported as 3.3% in cadaver dissections 38 . The retroaortic renal vein is usually drained into the IVC 56 , but can be drained into the common iliac vein 2 .
Circumaortic and retroaortic variants constitute the most common anomalies of the left renal vein with incidence of 6.2%-14% 10,57,58 . However, it is not contraindicated for laparoscopic live donor left nephrectomy in the presence of these anomalies. The excellent outcomes in both donor and recipient can be achieved in the experienced units 6,8,10 . Care must be taken to justify which component should be preserved for graft transplantation. Usually, the posterior segment of the circumaortic renal vein has a smaller size that can be safely divided and sacrificed. In Review the presence of renal vein anomalies, the insertion of the lumbar veins, gonadal vein and adrenal vein may be in various fashions. Therefore, careful review of the CTA prior to the surgery is mandatory to identify possible anomalies. The meticulous dissection is preferred in dealing with these venous anomalies to avoid the risk of injury and bleeding 8 . In the presence of a retroaortic left renal vein, the retroperitoneoscopic technique will provide an easy approach that is readily accessible to the abnormal veins 2,8 .

The value of CTA
The advent of multidetector row computed tomography (MDCT) enables comprehensive evaluation of the renal vasculature and has replaced conventional digital subtraction angiography (DSA). The renal artery and segmental arteries can be well visualised in the arterial phase, and veins can be evaluated in the venous phase including adrenal, gonadal, lumbar veins and their tributaries. In addition, the variations of renal vasculature can be well assessed by MDCT prior to surgery, which can provide accurate information to guide the laparoscopic donor nephrectomy 19,22,59 . The accuracy of MDCT for detection of renal vasculature anomalies ranged from 96% to 100% 16,[59][60][61][62][63] . Therefore, it is mandatory to review the donors' CTA care-fully prior to laparoscopic donor nephrectomy to minimise the risk of injury to the renal vasculature, in particular in the presence of vascular variations.

Conclusion
The renal vasculature anomalies are commonly encountered during live kidney donor work-up. The overall incidence is added to about 70% including supernumerary renal arteries, early renal artery bifurcation, dual renal veins, dual IVC and circumaortic/retroaortic renal veins. The accuracy of MDCT in detection of the renal vascular anomalies has been well demonstrated in the literature, and it is widely employed for live kidney donor work-up. In general, these variations are not contraindicated for consideration of laparoscopic donor nephrectomy and consequence of kidney transplant. However, it is paramount for surgeons to have thorough knowledge of renal vasculature development and to readily identify these anomalies of renal vasculature on CTA prior to laparoscopic donor nephrectomy. The surgical safety should be analysed on every individual case within the transplant unit. The adverse bleeding event can therefore be prevented.