Renal ectopic and fusion anomalies

INTRODUCTION — Renal ectopy and fusion are common congenital anomalies of the kidney and urinary tract (CAKUT) and result from disruption of the normal embryologic migration of the kidneys. Although children with these anomalies are generally asymptomatic, some children develop symptoms due to complications, such as infection, kidney stones, and urinary obstruction.

Ectopic and fusion anomalies of the kidney and their associated complications will be reviewed here. An overview and the evaluation of CAKUT, including radiologic investigations, are found separately. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)" and "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)".)

NORMAL EMBRYOGENESIS — Normal embryologic development of the kidney occurs in three stages: pronephros, mesonephros, and metanephros. The metanephros forms the permanent kidney and is first detected at five to six weeks of gestation (figure 1). The metanephros is composed of the metanephric mesenchyme and ureteral bud (caudal portion of the mesonephric duct).

The metanephros is initially positioned in the pelvis opposite the sacral somites. Rapid caudal growth results in the migration of the developing kidney from the pelvis to the retroperitoneal renal fossa, which lies on either side of the spine opposite the second lumbar vertebra. As each kidney ascends, it rotates through 90° such that the renal hilum is directed medially as the kidney reaches its final position. Migration and rotation are completed by the eighth week of gestation.

The ascending kidney derives its vascular supply locally from neighboring vessels. As the kidneys reach their permanent position, renal arteries and veins develop and provide vascular support. Ectopic kidneys usually contain numerous additional small vessels, reflecting the continuous changes in blood supply of the developing kidneys during renal ascent.

Positional (ectopy) and fusion anomalies occur when this normal embryogenic migration is disrupted and are discussed in the following sections.

PATHOGENESIS

Renal ectopy — Renal ectopy occurs when the kidney does not normally ascend to the retroperitoneal renal fossa (level of the second lumbar vertebra).

●Simple ectopy refers to a kidney that lies on the correct side of the body but in an abnormal position.

●Crossed renal ectopy refers to a kidney that crosses the midline. Crossed renal ectopy can occur with and without fusion to the contralateral kidney (figure 2). (See 'Crossed fused ectopy' below.)

Ectopic kidneys that do not ascend above the pelvic brim are commonly called pelvic kidneys. Rarely, the ectopic kidney is found in the thorax [1,2]. Bilateral renal ectopy has also been reported but is rare [3].

The ectopic kidney fails to rotate normally, resulting in a shift of the renal axis so that the renal pelvis is directed anteriorly rather than medially. The blood supply of the ectopic kidney is variable and may come from the iliac arteries, aorta, and, at times, the hypogastric and middle sacral arteries, reflecting the continuous changes in blood supply of the developing kidneys during renal ascent. (See 'Normal embryogenesis' above.)

Renal fusion — Renal fusion occurs when a portion of one kidney is fused to the other. The most common fusion anomaly is the horseshoe kidney.

Horseshoe kidney — The most common renal fusion anomaly is the horseshoe kidney, which involves abnormal migration of both kidneys (ectopy), resulting in fusion of each kidney (figure 3). In more than 90 percent of cases, fusion occurs at the lower poles; as a result, two separate excretory renal units and ureters are maintained. The isthmus (fused portion) may lie over the midline (symmetric horseshoe kidney) or lateral to the midline (asymmetric horseshoe kidney). Depending on the degree of fusion, the isthmus can be composed of renal parenchyma or a fibrous band.

Fusion is thought to occur before the kidneys ascend from the pelvis to their normal dorsolumbar position. This is usually between the fifth and ninth weeks of gestation. The majority of horseshoe kidneys with a parenchymal isthmus result from an abnormal migration of the posterior nephrogenic area, which generally occurs before the fifth week of gestation [4,5]. Horseshoe kidneys with a fibrous isthmus arise from fusion after the fifth week of gestation, before renal ascent. If large portions of the renal parenchyma fuse, the fusion anomaly loses its horseshoe appearance and appears as a flattened disc or lump kidney.

Early fusion also causes abnormal rotation of the developing kidneys. As a result, the axis of each kidney is shifted so that the renal pelvis lies anteriorly and the ureters either traverse over the isthmus of the horseshoe kidney or the anterior surface of the fused kidney (figure 3).

Fusion anomalies seldom ascend to the dorsolumbar position of normal kidneys and are typically found in the pelvis or at the lower lumbar vertebral level (L4 or L5). The blood supply of the fused kidney is variable and may come from the iliac arteries, aorta, and, at times, the hypogastric and middle sacral arteries [6].

Crossed fused ectopy — In crossed fused ectopy, the ectopic kidney and ureter cross the midline to fuse with the contralateral kidney, but the ureter of the ectopic kidney maintains its normal insertion into the bladder. In most cases, the ectopic kidney is positioned inferiorly to the contralateral kidney (figure 2). The contralateral kidney can either retain its normal dorsolumbar position or is positioned lower in the pelvis or lower lumbar vertebral level (L4 or L5).

EPIDEMIOLOGY — The incidence of renal ectopic and fusion anomalies is uncertain as its frequency varies by the mode of detection and, thus, published reports may not accurately reflect the rate of these renal anomalies.

●Renal ectopy – The reported incidence of renal ectopy ranges from 2 to 10 per 10,000 depending on the mode of detection (autopsy, antenatal ultrasonography, screening ultrasonography) [7,8]

●Crossed fused ectopy – The estimated incidence of crossed fused ectopy from autopsy data is approximately 1 in 2000 [9]

CLINICAL PRESENTATION

Renal ectopy — The majority of patients with renal ectopy are asymptomatic. The diagnosis is often made coincidentally during routine antenatal or postnatal ultrasonography [10].

●Antenatal presentation/empty renal fossa – In a fetus with normal amniotic fluid volume, the most likely cause of an absent kidney in the renal fossa is an ectopic kidney. In a retrospective review of 40 cases of empty renal fossa detected on antenatal ultrasonography, renal ectopy was the underlying cause in 25 (24 simple, 1 crossed), horseshoe kidney in 2, and renal agenesis in 13 [7]. The finding of an empty renal fossa during antenatal ultrasonography should prompt search for an ectopic kidney.

●Symptomatic presentation – In patients diagnosed symptomatically, findings at presentation are generally related to associated complications, such as urinary tract infection (UTI), urinary obstruction, and kidney stones. Symptoms include abdominal pain, fever, hematuria, or incontinence from an ectopic ureter or small ectopic pelvic kidney. On examination, an abdominal mass may be palpable or hypertension detected. Rarely, in female patients, persistent urinary incontinence characterized by continuous dampness of underwear can be secondary to a small ectopic pelvic kidney with insertion of the ureter into the urethra [11,12].

In a case series of 99 patients with renal ectopy, among the 20 symptomatic patients, 12 had signs of UTI, 4 had abdominal pain, 2 had a palpable abdominal mass, 1 had hematuria, and 1 was incontinent [10]. (See "Ectopic ureter".)

Horseshoe kidney — The majority of patients with horseshoe kidneys are asymptomatic and present incidentally due to detection by antenatal ultrasonography.

●Asymptomatic presentation – Most patients with renal fusion are asymptomatic and are detected coincidentally usually by antenatal ultrasonography. Hydronephrosis, which is commonly detected by antenatal ultrasonography, has been reported to occur in as many as 80 percent of children with horseshoe kidneys and, even if asymptomatic, may require further diagnostic workup. [13,14].

●Symptomatic presentation – Symptomatic patients present with pain and/or hematuria due to urinary obstruction or infection.

•Urinary obstruction – Obstruction of the collecting system is caused by congenital ureteropelvic junction obstruction (UPJO), kidney stones, or external ureteric compression by an aberrant vessel. (See 'Associated urologic abnormalities' below.)

•Infection – Patients with a horseshoe kidney are at increased risk for infection because of the increased likelihood of lower urinary tract anomalies.

ASSOCIATED CONDITIONS

Associated urologic abnormalities — Other urologic abnormalities are commonly observed in children with renal ectopy and fusion anomalies [15].

●Vesicoureteral reflux (VUR) is a common associated condition for individuals with renal ectopy and fusion anomalies. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

•Renal ectopy – VUR is reported in approximately one-third of all cases of renal ectopy, with higher prevalence with simple ectopia [10,15]. In a case series of 99 patients with renal ectopy, VUR occurred in 20 percent of crossed renal ectopy (n = 20), 30 percent of simple renal ectopy (n = 82), and 70 percent of bilateral simple renal ectopy (n = 7) [10]. In another series of 68 children, 30 percent of those with simple renal ectopia had VUR, with no VUR reported in those with crossed ectopia [16].

•Horseshoe kidney – The reported prevalence of VUR is lower in case series of patients with horseshoe kidneys, ranging from 10 to 25 percent [17,18].

●Ureteropelvic junction obstruction (UPJO) is commonly observed in individuals with a horseshoe kidney. This is likely due to the high insertion of the ureters into the renal pelvis and displacement of the fused isthmus [19]. In a case series of 52 individuals with horseshoe kidneys, UPJO was noted in 12 patients [17]. Of note, UPJO is a common finding for individuals with crossed renal ectopy or pelvic kidney but occurs less frequently in patients with simple nonpelvic ectopy [10,20]. (See "Congenital ureteropelvic junction obstruction".)

●Kidney stones – Kidney stones are reported to occur in 20 percent of cases of horseshoe kidneys (image 1). Contributing factors to the development of kidney stones in these patients include urinary stasis, increased risk of infection, and, possibly, metabolic abnormalities (including hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia) [21].

●Other reported urologic abnormalities ‒ Other reported urologic abnormalities include renal dysplasia in children with renal ectopy [10], and, for children with horseshoe kidney, reported abnormalities include ureteral duplication, ectopic ureter, ureterocele, and a retrocaval ureter [14].

Genital anomalies

●Males – Genital anomalies in males with renal ectopic and fusion anomalies include hypospadias and cryptorchidism [10]. (See "Hypospadias: Pathogenesis, diagnosis, and evaluation", section on 'Diagnosis' and "Undescended testes (cryptorchidism) in children: Clinical features and evaluation", section on 'Examination'.)

●Females – In females, reported genital anomalies include agenesis of the uterus and vagina (eg, Müllerian agenesis and Mayer-Rokitansky-Küster-Hauser syndrome), unicornuate uterus bicornuate, and/or septate uterus [22,23]. In girls with uterovaginal atresia, there is often only a single ectopic kidney. In these patients, as well as those with contralateral renal dysplasia, kidney function is impaired. (See "Congenital uterine anomalies: Clinical manifestations and diagnosis" and "Congenital anomalies of the hymen and vagina".)

Nongenital-urinary abnormalities

●Renal ectopy – Ectopic kidney can be associated with nonrenal anomalies (adrenal, cardiac, and skeletal abnormalities) and as a clinical feature in syndromes. Thoracic kidneys are often associated with congenital diaphragmatic hernia [2]. In a retrospective case series from a single center, 3 of 41 patients were diagnosed with a specific syndrome (ie, Treacher Collins, Mayer-Rokitansky-Küster-Hauser, and Goldenhar syndromes) [15].

●Horseshoe kidneys

•Syndromes – Horseshoe kidney can be a feature of many syndromes including genetic disorders such as Turner syndrome and trisomy 13, 18, and 21 [24]. (See "Clinical manifestations and diagnosis of Turner syndrome" and "Congenital cytogenetic abnormalities", section on 'Numeric abnormalities'.)

In one series of 380 children and young adults with horseshoe kidneys, 50 percent had extrarenal diseases or syndromes, including 16 percent with gastrointestinal tract anomalies, 14 percent with vertebral anomalies, 4 percent with Turner syndrome, and 2.5 percent with caudal regression syndrome [18].

•Wilms tumor – Patients with a horseshoe kidney appear to have an increased risk for Wilms tumor. In a retrospective review of 8617 patients from the National Wilms Tumor Study between 1969 and 1998, 41 patients were identified with Wilms tumor in a horseshoe kidney [25]. (See "Presentation, diagnosis, and staging of Wilms tumor".)

EVALUATION — For individuals with renal ectopy and fusion anomalies, evaluation includes careful physical examination and imaging to detect other anomalies and assessment of kidney function.

●Physical examination – The physical examination can detect genital anomalies (eg, hypospadias and cryptorchidism) and nongenital-urinary features associated with genetic disorders and syndromes. (See 'Associated conditions' above.)

●Imaging

•Postnatal kidney ultrasonography – For infants diagnosed antenatally, postnatal kidney ultrasonography is performed to confirm the diagnosis of renal ectopy or fusion and defines underlying kidney and urologic anatomy, including the presence of hydronephrosis.

•Voiding cystourethrogram (VCUG) – VCUG is used to determine whether vesicoureteral reflux (VUR) is present. A VCUG is not indicated in all patients despite the relative high incidence of VUR in patients with an ectopic or horseshoe kidney, since VUR alone is not viewed as a risk to long-term kidney function. In the author's center, VCUG is considered in patients who present with a urinary tract infection (UTI) or hydronephrosis. (See "Urinary tract infections in infants older than one month and children less than two years: Acute management, imaging, and prognosis", section on 'Voiding cystourethrogram' and "Postnatal evaluation and management of hydronephrosis", section on 'Subsequent evaluation and management'.)

•Renal radionuclide scans

-Static renal scan with 99mTc–dimercaptosuccinic acid (DMSA) detects renal parenchyma and provides differential assessment of kidney function. It can be used to find a small ectopic kidney (nubbin) that is not identified by kidney ultrasound in a patient with an empty renal fossa. It also can identify defects in renal architecture (eg, developmental dysplasia, scarring) and compare function of the affected kidney with the normal contralateral kidney. In a case series, decreased renal function was detected by DMSA renal scan in 74 of 82 cases of simple unilateral renal ectopy [10]. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Static renal scan'.)

-Dynamic renal scans with 99mTc-mercaptotriglycylglycine (MAG-3 or MAG3) is used to detect urinary obstruction for infants with severe hydronephrosis and a normal VCUG. In some cases, a diuretic (furosemide) is used to optimize urinary flow and is referred to as a diuretic renograph. (See "Postnatal evaluation and management of hydronephrosis", section on 'Diuretic renography'.)

•Kidney function – Serum creatinine (SCr) concentration is used clinically to assess kidney function. Measurement of creatinine is commonly performed at least once during the clinical management of patients with any form of congenital anomaly of the kidney and urinary tract (CAKUT). For renal ectopia and horseshoe kidney, SCr should be monitored when there exists any uncertainty regarding the level of kidney function, including those with bilateral kidney disease, those with solitary kidney with abnormal appearance and/or growth, or if there is uncertainty regarding the functional status of the contralateral kidney.

In our practice, evaluation is based on the results of imaging and kidney functional assessment:

●For the individual with a normal-appearing contralateral kidney and no evidence of hydronephrosis on kidney ultrasound, no further initial evaluation is required, although follow-up is recommended every two years. Follow-up clinical management typically monitors growth of the contralateral kidney by ultrasound and measures SCr to assess kidney function.

●Additional evaluation by DMSA renal radionuclide scan is performed to identify functional renal tissue, differentiate kidney function between kidneys, and detect any evidence of kidney scarring. Scan is suggested for individuals with:

•Elevated SCr

•Abnormal-appearing contralateral kidney

•Ultrasound showing indistinct tissue in the renal fossa or empty renal fossa and inability to detect ectopic kidney

●Patients with severe hydronephrosis not due to VUR (ie, normal VCUG) should be evaluated by a dynamic radionuclide renal scan with either MAG-3 or DTPA to differentiate hydronephrosis due to obstruction from nonobstructive urinary stasis [26]. If obstruction is present, a urologic consultation should be sought. (See "Postnatal evaluation and management of hydronephrosis", section on 'Diuretic renography'.)

●Patients with mild or moderate hydronephrosis not due to VUR are reevaluated by ultrasonography three to six months later. If there is progressive hydronephrosis, a MAG-3 or DTPA diuretic renogram should be performed to detect obstruction. If there is improvement or no change in the degree of hydronephrosis, monitoring is continued with subsequent ultrasound. (See "Postnatal evaluation and management of hydronephrosis", section on 'Persistent moderate to severe hydronephrosis'.)

A more complete description of the radiologic studies discussed is reviewed separately. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)".)

MANAGEMENT AND PROGNOSIS — Evidence is limited regarding long-term outcome and management.

●Renal ectopy – Data on outcome of individuals with renal ectopia are very limited and appear to be restricted to school-age children. In one case series of 41 patients with a median age at diagnosis of 0.2 years, follow-up assessment at 7.7 years demonstrated normal blood pressure and no evidence of albuminuria [15]. However, estimated glomerular filtration rate was less than 90 mL/minute per 1.73 m² in nine children but remained stable without evidence of deterioration. There was no difference in outcome data between patients with simple ectopy (n = 26) versus those with crossed ectopia (n = 15).

●Horseshoe kidney – Available data suggest that individuals with horseshoe kidneys are at risk for chronic kidney disease:

•A follow-up study in 146 adults (mean age 43 years) with horseshoe kidney reported that the horseshoe group compared with matched controls (ie, sex, age, serum creatinine [SCr], hypertension) had higher rates of urinary tract obstruction, kidney stones, urogenital cancer, and end-stage kidney disease [27].

•In another case series of 41 children (aged 2 months to 16 years with a median of four years of follow-up), kidney scarring was found in 24 percent, proteinuria in 15 percent, and hypertension in 10 percent, with progression to chronic kidney disease in 7 percent of the cohort [28].

Based on these (albeit limited) reports, individuals with known renal ectopic and fusion anomalies are monitored intermittently for potential complications and kidney function. In our center, investigations through adolescence (ie, postpuberty) occur every two years with a kidney ultrasound to assess kidney size and interval growth, measurement of SCr and blood pressure, and a urinalysis to screen for proteinuria. Annual assessment of blood pressure and periodic urinalysis are recommended in the adult years. No restrictions of activity are recommended, since there are no data to support such restrictions.

Other management issues include:

●Vesicoureteral reflux (VUR) – The management of VUR including prophylactic antibiotic is discussed separately. (See "Management of vesicoureteral reflux".)

●Obstructive uropathy – Patients with evidence of obstructive uropathy are referred to a urologist with expertise in managing obstructive uropathy. Obstruction is primarily due to ureteropelvic junction obstruction (UPJO). (See "Congenital ureteropelvic junction obstruction".)

●Surgery – If surgery is required, computed tomographic angiography may be needed to characterize vascular anatomy as the vascular supply can be anomalous to both the ectopic and nonectopic kidneys [29].

SUMMARY AND RECOMMENDATIONS

●Pathogenesis – Renal ectopic and fusion anomalies are due to disruption of the normal embryogenic process (figure 1). (See 'Normal embryogenesis' above.)

•Renal ectopy is a positional abnormality with failure of the kidney(s) to normally ascend to the retroperitoneal renal fossa (level of the second lumbar vertebrae). Simple renal ectopy refers to a kidney that lies on the correct side but in an abnormal position, and crossed renal ectopy refers to a kidney that crosses the midline to the contralateral side (figure 2). (See 'Renal ectopy' above.)

•Renal fusion occurs when a portion of one kidney is fused to the other. The most common fusion anomaly is the horseshoe kidney, which involves abnormal migration of both kidneys (ectopy), resulting in fusion (figure 3). Crossed fused renal ectopia, another renal fusion anomaly, usually involves abnormal movement of only one kidney across the midline, with fusion of the contralateral noncrossing kidney (figure 2). (See 'Renal fusion' above.)

●Clinical presentation – Most patients with an ectopic or fused kidney(s) are asymptomatic and are diagnosed incidentally, often by antenatal ultrasonography. In symptomatic patients with either anomaly, complaints at presentation are generally related to associated complications including urinary tract infection (UTI), urinary obstruction, and kidney stones. (See 'Clinical presentation' above.)

●Associated conditions – Patients with renal ectopy or fused kidneys are at increased risk for other anomalies, especially genitourinary abnormalities such as vesicoureteral reflux (VUR) and complications including UTI, urinary obstruction, and kidney stones. (See 'Associated conditions' above.)

●Evaluation (see 'Evaluation' above):

•Initial evaluation for either renal ectopy or fusion includes the following three studies.

-Ultrasonography to confirm renal ectopy or fusion; determine the presence/absence of hydronephrosis; measure kidney size in the ectopic, contralateral, and/or fused kidney; and assess anatomy of the contralateral kidney.

-Measurement of serum creatinine (SCr) to assess kidney function.

-In patients with UTI or hydronephrosis, voiding cystourethrogram (VCUG) to determine presence/absence of VUR.

•Further evaluation depends on the results of these initial tests and may include renal scintography.

●Management and prognosis (see 'Management and prognosis' above):

•Outcome – Although outcome data are limited, case series suggest that individuals with renal ectopic or fusion anomalies are at risk for long-term renal sequalae compared with those without these anomalies. These include decreased renal function and higher rates of urinary tract obstruction, kidney stones, urogenital cancer, and end-stage kidney disease.

•Long-term monitoring – In our center, individuals with renal ectopic and fusion anomalies are regularly monitored for kidney growth and potential complications including urinary tract obstruction, kidney stones, UTI, and kidney function impairment. Follow-up management includes kidney ultrasound, SCr and blood pressure measurement, and urinalysis.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Aoife Waters, MD, PhD, FRCPCH, who contributed to earlier versions of this topic review.