Journal of Pediatric Urology (2016) 12, 275e280
The horseshoe kidney: Surgical anatomy and embryology K. Taghavi a,b, J. Kirkpatrick c, S.A. Mirjalili d a
Department of Paediatric Surgery, Wellington Children’s Hospital, Wellington, New Zealand
Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
c School of Medicine, University of Auckland, Auckland, New Zealand
Department of Anatomy, University of Auckland, Auckland, New Zealand Correspondence to: S.A. Mirjalili, Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand, Tel.: þ64 9 923 7487 [email protected]
(S.A. Mirjalili) Keywords Horseshoe kidney; Renal fusion; Renal ectopia; Ectopic kidney Received 19 December 2015 Accepted 10 April 2016 Available online 31 May 2016
Summary Horseshoe kidneys are a common, yet enigmatic, renal malformation. This review critically appraised the literature surrounding the embryology, etiology and clinical anatomy of horseshoe kidneys. The systematic literature search produced 104 articles, and 56 primary and further secondary references. There were several etiological theories regarding horseshoe kidneys. The established view was that during ascent, the kidneys come into close apposition as they pass through an arterial fork. Another possible mechanism related to lateral flexion of the trunk or rotation of the caudal embryo; the association of asymmetrical horseshoe kidneys with a number of vertebral conditions supported this hypothesis. More recent animal models implicated the
notochord and sonic hedgehog signaling. Furthermore, it has been suggested that the isthmus may be the result of ectopic mesenchymal tissue. Surgical anatomy of the horseshoe kidney is complex, due to variability in location, orientation and blood supply. Both arterial and venous anatomy is highly variable. This raised the question of whether anomalous blood supply is the cause or result of abnormal renal position. In the majority of cases, the isthmus contained functional renal parenchyma. In over 90% of cases, fusion between the kidneys occurred at the lower pole. Despite commonly being quoted as ‘held back by the inferior mesenteric artery’ at L3, in reality the isthmus was only found immediately inferior to this in 40% of cases.
Horseshoe kidneys are the most common fusion defect of the kidney, with a reported frequency of approximately 1:500 . They were first described during autopsies performed by da Carpi in 1522 and are characterized by abnormalities in three major domains: renal position, rotation and vascular supply . Several etiological factors may contribute to the development of a horseshoe kidney, including: the intrauterine environment, genetic/chromosomal predisposition, and structural factors that affect the development and migration of the kidneys . Horseshoe kidneys have important clinical relations with regards to: secondary renal pathology, associated syndromes, and subsequent malignancy. Although many articles have been written regarding renal fusion and ectopia, there is a scarcity of comprehensive reviews that systematically abridge the current understanding of this malformation. This study critically appraised the literature surrounding the clinical anatomy, etiology, and embryology of horseshoe kidneys.
A systematic literature search was performed using Scopus and PubMed. Search terms included were: ‘Horseshoe Kidney’, ‘Ectopic’ or ‘Fusion’ and ‘Kidney’ or ‘Renal’, ‘Urogenital’ or ‘Urinary’ and ‘Malformation’, ‘Horseshoe kidney’ and ‘Surgery’. A total of 104 journal articles and textbook references were retrieved and reviewed. Primary articles were systematically reviewed and secondary references were obtained and subsequently reviewed with relevance to embryology, etiology and surgical anatomy. The search was restricted to English-language articles but no date restriction was placed. Finally, 56 primary and 12 secondary references were reviewed. The 42 references included in the final manuscript have been abbreviated to reduce redundancy and to meet the journal’s requirements.
Embryology and etiology From an embryological point of view, each kidney consists of two distinct cell
http://dx.doi.org/10.1016/j.jpurol.2016.04.033 1477-5131/ª 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
276 populations: the ureteric bud and the metanephric blastema. The ureteric bud forms the collecting system, while the functioning kidney is derived from the metanephric blastema. These two structures meet in the upper sacral region (S1eS2) through reciprocal induction during the fourth week of development . Aberrations of this process are responsible for a wide spectrum of congenital urological conditions . Reference textbooks quote renal fusion anomalies as occurring between 4 and 6 weeks of development [6,7]. Other authors allow for a time frame of up to 9 weeks, particularly in cases of a fibrous isthmus [5,8]. There are numerous hypotheses regarding the cause of horseshoe kidneys, and they represent a common end-point of multiple etiologies. The various mechanisms can be considered as: positional factors and anomalous fusion related to proximity, abnormalities in migration of metanephric cells, intrauterine factors (maternal environment and exposure to teratogens), and associated genetic factors and chromosomal abnormalities .
Physical environment Fusion defects may be caused by abnormal fluctuations in growth and ventral flexion of the caudal fetus within a confined true pelvis . It has been confirmed that the metanephric blastemas in normal embryos are in close proximity to each other prior to ascent . The
K. Taghavi et al. established view is that during ascent (as depicted in Fig. 1B), they come into close apposition as they pass through an arterial fork . However, there are inconsistencies around which anatomical entity this occurs: the aortic bifurcation [6,12] or the umbilical arteries [13,14]. Generally, the more complete the fusion, the more ectopic the position . Also, during renal ascent, flexion or rotation of the caudal end or spine (even within normal developmental variability) may be sufficient to cause fusion . In a similar manner, even slight alterations in the position of key arteries (e.g., umbilical or common iliac) may cause an alteration in the path of renal migration and consequent fusion . A related point to note is that even in normal individuals, both kidneys share a common perirenal space (crossing the midline) . The fact that fusion anomalies may occur both symmetrically or asymmetrically provides further insights into causation (distribution of these variants are depicted in Fig. 2) . Symmetrical horseshoe kidneys are presumed to result from factors that influence both renal masses equally . These may include abnormalities of growth or ventral flexion within a constricted embryonic pelvis . Also, delayed straightening of the caudal fetus may postpone renal ascent allowing fusion to occur . Asymmetrical or laterally fused horseshoe kidneys are the result of differential displacement of the renal masses . Etiology of these may include lateral flexion of the trunk or rotation of
Figure 1 Ascent of the developing kidney. A. Normal kidney position and incidence of ectopia with horseshoe kidneys . B. Normal morphological and positional changes in the kidney during development with relation to the vertebral column and umbilical artery, based on studies of human embryos . The diagrams represent the following gestational ages: a) 6 weeks þ 3 days; b) 7 weeks þ 1 day; c) 7 weeks þ 2 days; d) 8 weeks þ 3 days; e) 9 weeks þ 2 days.
Surgical anatomy and embryology the caudal embryo . The association of asymmetrical horseshoe kidneys with a number of vertebral conditions supports this hypothesis (e.g., scoliosis, vertebral agenesis, hemivertebra and spina bifida) [4,9,17]. The genitourinary system and vertebral column originate from distinct components of the mesoderm, but are relatively synchronous in their development, and so this association may also represent a developmental field defect or sequence .
Abnormal metanephric migration It has been suggested that the etiology of the characteristic isthmus or bridge may be due to ectopic mesenchymal tissue rather then ‘primary fusion’. This has followed the observation that in the majority of horseshoe kidneys, the ‘isthmus’ is composed of substantial parenchymal tissue (as in Fig. 2) . This ectopic nephrogenic tissue is said to arise due to incomplete or abnormal migration of posterior nephrogenic cells across the primitive streak [5,19]. This anomalous proliferation of the metanephric blastema may explain the propensity to certain tumors in horseshoe kidneys .
Genetic and autosomal disorders No clear genetic cause of horseshoe kidney has been described in humans; however, a number of regulatory steps in kidney development have not been fully elucidated and may offer future insight into etiology . In animal models, the notochord has been implicated as determining the position of metanephric tissue. Furthermore, depletion of the axial source of Sonic Hedgehog (SHH) has been shown to be sufficient to cause renal fusion, even in the presence of the notochord .
277 There is a well-described male preponderance (2:1) . Also, there are case reports of familial clustering between father and son  and monozygotic twins . In one family, three siblings had horseshoe kidneys and the mother had a malrotated kidney . This offers circumstantial evidence that fetal genetic programming may play an etiological role. However, there are also case reports of monozygotic twins where only one child is affected . Some authors contend that urological malformations associated with chromosomal abnormalities are partly a consequence of delayed development of the nephrogenic blastema and the ureteric bud . In Edwards syndrome horseshoe kidneys occur in two-thirds of patients , and in Downs syndrome the incidence of horseshoe kidneys is probably <1% . In Turner syndrome, horseshoe kidneys occur in 14e20% of patients , with a lower incidence of renal malformations in those with mosaicism .
Anatomy of the horseshoe kidney Renal isthmus and its relations The bridge connecting the two renal masses has variable anatomical relations and substance (as depicted in Fig. 2). Its midline or lateral position, relative to the vertebral column, establishes whether the horseshoe kidney is symmetric or asymmetric . Asymmetrical systems are more commonly left dominant (70%) . In 80% of cases, the isthmus contains functional renal parenchyma, which can provide a challenge to safely divide at surgery. In over 90% of cases, fusion between the kidneys occurs at the lower pole; although it may also occur at the upper pole, resulting in an ‘inverted horseshoe’ (5e10%), or at both poles resulting in a ‘disc kidney’ [8,31]. There may also be double ureters present on one or both sides (6%) . One or both ureters may rarely travel posterior to the isthmus . The isthmus typically crosses anterior to the great vessels, but can cross posteriorly, or even more rarely run between them [32,33].
Migration and location
Figure 2 Incidence of the various morphological configurations of horseshoe kidneys and their isthmus .
The developing kidneys initially lie adjacent to each other below the umbilical arteries in the embryonic pelvis at 4  to 5  weeks of gestation (5-mm or 7-mm human embryo). During their relative ascent, they become anatomically separated to reach their final positions in the retroperitoneal renal fossa . The kidneys ascend out of the pelvis during the seventh week and have reached their final position by the end of the eighth [4,8] or ninth  week (see Fig. 1). This occurs due to disproportionate growth of lumbar and sacral regions in conjunction with general straightening of the embryo. This results in the body wall shifting inferiorly, with relative ascent of the kidney [6,12]. During migration, the shape of the developing kidneys fluctuates: it becomes thin and oblong while passing the narrow space of the umbilical arteries before rounding out to take on the mature form and position . Horseshoe kidneys generally don’t migrate superiorly to the same extent . The ascent of these kidneys is often quoted to be ‘held back by the inferior mesenteric artery’
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Graves’ description of the various segmental arterial patterns of horseshoe kidneys .
at L3 [6,13,33]. However, in reality, the isthmus is only found immediately inferior to the inferior mesenteric artery in 40% of cases; a further 20% never leave the pelvis (see Fig. 1) [7,33].
Rotation During weeks 6e8 of development, renal ascent is coupled with a 90 medial rotation . This results in the hilum rotating from an anterior to a medial position, as well as a tilt in the renal axis, with the upper pole lying posteromedial relative to the lower pole . The spectrum of abnormalities in horseshoe kidney include malrotation, and consequently the ureters either pass over the isthmus or down the anterior surface of the kidneys [8,33]. The most common occurrences are incomplete rotation or nonrotation, however, hyper-rotation and reverse rotation can also occur .
Blood supply The developing kidney gains and loses several sources of vascular supply during ascent . In the pelvis, the median sacral artery and the internal and external iliac vessels supply it. Later, it may be directly supplied by the aorta, or a branch from it (the common and inferior mesenteric artery), before gaining the renal artery . As cranial migration continues, the caudal arteries degrade . Reports have demonstrated inhibition of cranial migration via persistent embryonic arteries . This raises the question of whether these anomalous blood vessels are the cause or result of abnormal renal position. This point requires particular clarification in the case of an inverted horseshoe kidney, and when there are variable relations to the great vessels .
Ectopic kidneys show great variation in: origin, number, and size of renal arteries and veins, depending on where during development ascent has terminated . Due to the surgical significance of these variations, attempts have been made to map the arterial supply [1,31,37]. Graves considered the vascular pattern of horseshoe kidneys in six groups (see Fig. 3) . However, this is a simplification of highly variable vascular anatomy and does not allow for arteries that supply contralateral kidney tissue (this occurs in approximately 25% of horseshoe kidneys). Furthermore, this system does not describe the wide range of possible arterial origins that include the: common iliac artery (40%), median sacral artery (3%), lumbar artery (3%), internal iliac artery (2%), external iliac artery (1%) and phrenic artery (0.97%) . More contemporary studies have employed modern imaging techniques to describe the extensive variation of the vascular anatomy, and general conclusions can be drawn. In a study of 90 horseshoe kidneys, 387 feeding arteries were identified (on average two or more arterial supplies per renal unit), with more arteries supplying the right side (219 vs 168) . The most cranial of the renal arteries were more consistent in position, and arose more posteriorly from the aorta when compared with those originating caudally. The percentage of vessels originating from the aorta decreased with number from 99% for the first arising artery to 50% for the fifth . Nevertheless, even in horseshoe kidneys, the normal vascular segmental pattern remains . Although these vessels are considered anomalous, their ligation or division results in ischemic necrosis due to their autonomous supply . The blood supply of the isthmus carries particular interest and exhibits considerable variation; it may, in some cases, supply the entire kidney . The isthmus may receive its blood supply from: the main renal artery, a branch from the abdominal aorta (originating above or
Surgical anatomy and embryology below the isthmus), the common iliac artery or the inferior mesenteric artery [2,39]. The incidence of renal vein anomalies in horseshoe kidneys is also high (23%) . Anomalous veins in the horseshoe kidney commonly drain into either the vena cava or iliac veins . Variations of inferior vena cava (IVC) anatomy (including double IVCs and left IVCs) are observed ten times more frequently in those with horseshoe kidneys (5.7%) . Important variations in vascular supply can make upper tract surgery, kidney transplant or surgical and endovascular procedures challenging . Indeed, operating on horseshoe kidneys has been described as a ‘minefield for open vascular surgery’ .
Conclusion Horseshoe kidneys reveal a veritable range of anatomical and embryological peculiarities. There are multiple mechanical and genetic associations that have been implicated. The close apposition of the renal blastemas during renal ascent may play an important role in their development. Their relative migration is incomplete, resulting in a final position ranging from the normal renal fossa to the true pelvis. Their medial rotation is also interrupted and results in a more anterior pelvis and ectopic ureter path. Their arterial relations and supply are highly variable. Furthermore, they are associated with various ureteric configurations and venous anomalies. These have important implications in operative planning.
Conflict(s) of interest None to declare.
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