Unilateral Renal Agenesis

Unilateral renal agenesis (URA) is defined as complete absence of one kidney and ipsilateral ureter.

Unilateral renal agenesis (URA) occurs in 1-2/1000 births. It is found more frequently in males and the missing kidney is more frequently the left one. It is also more common in twins than in singletons.^1,2

This anomaly is due either to failure of the development of the ureteric bud, or to a defect of its interaction with the metanephric blastema,¹ involving just one side of the urinary tract. The defect in embryogenesis occurs at around 5 weeks of embryonic life.

The unilateral absence of kidney is not correlated with a reduction of the overall renal function, as the amniotic fluid and the bladder filling are normally represented. During prenatal life, the clearance function is provided mainly by the placenta.³ Hypertrophy of the contralateral kidney is frequently associated, ^4,5 and is apparently due to a renotropic humoral growth factor.

In case of unilateral renal agenesis, the risk of chromosomal anomalies is low (1%). The structural anomalies most frequently associated with this condition¹ affect the contralateral kidney and the internal genital organs (not visible in the prenatal period). The contralateral kidney could be enlarged (compensatory hypertrophy, about 80% of cases)⁴ and/or displaced.

The association with genital anomalies is related to a common embryologic origin: Mullerian duct derivatives (uterus, vagina) could be abnormal or atretic in females, as well as Wolffian duct derivatives (seminal vescicles, vas deferens) in males. In males there is a significant association (12%) with absence of the seminal vescicles and vas deferens, and seminal vescicle cyst. In 40% of females, bicornuate or unicornuate uterus, ipsilateral blind vaginas and mullerian duplications could be found.²

In up to 40-50% of children referred for evaluation, an association with urinary tract obstruction or reflux of the contralateral kidney has been reported. Bladder extrophy, anal atresia, malrotation, Mekel diverticulum and lumbosacral vertebral defects could be also associated.^1,6,7 The ipsilateral adrenal gland is usually present and characterized by a rounder shape, but adrenal agenesis has also been reported (10% of the cases of URA.)⁸

These features are often part of a more complex syndrome (or associations) where the renal agenesis could be just one sign.^1,9 The most common are:

• VA(C)TER(L) association (renal agenesis, vertebral anomalies, anal atresia, cardiac abnormalities, trachea-esophageal fistula and limb anomalies),
• Caudal regression syndrome (renal agenesis, sacral agenesis, lumbar vertebral anomalies and femoral hypoplasia),
• Cerebro-oculo-facial-skeletal syndrome (renal agenesis, microcephaly, micrognathia and joint contractures),
• Otocephaly (renal agenesis, agnathia, microstomia, holoprosencephaly and cleft lip/palate),
• Rokitansky-Kuster-Hauser syndrome (renal agenesis, bicornuate uterus and vaginal atresia).

X-linked, autosomal dominant and recessive inheritance have been reported for renal agenesis.¹⁰ If renal agenesis is isolated, the empiric risk of recurrence is 3-6%, whereas if it is one sign of a syndrome, the risk of recurrence is obviously the risk associated with the underlying syndrome.

Many cases of renal agenesis have shown a multifactorial inheritance. A significant proportion of relatives (mainly parents or siblings) of fetuses with renal agenesis have silent malformations of the urinary tract.¹¹ This evidence implies the presence of a genetic factor with autosomal dominant inheritance and variable expression, justifying the definition of these conditions as “hereditary renal agenesis”.¹²

The finding of a renal agenesis in one of the parents increases the recurrence risk to 15-20%.¹ In particular, in cases of autosomal dominant inheritance pattern, the recurrence risk could be up to 50%, whilst in recessive ones it is 25%.¹³

A certain number of cases of unilateral renal agenesis escapes prenatal diagnosis because, on the contrary of bilateral renal agenesis, in URA, no indirect signs raising the suspicion of this renal disease are present. In fact the bladder and amount of amniotic fluid are normal. Moreover, the presence of the adrenal gland in the ipsilateral renal loggia may resemble the kidney: in fact, due to the absence of the kidney, this gland may appear rounder than normal and fills the renal fossa¹⁴ in what has been termed the “lying down” adrenal sign.¹⁵

Color/power Doppler can be used in cases that are uncertain to confirm the absence of the ipsilateral renal artery.^9,16 In the third trimester, the findings of an enlarged kidney contralateral to the empty renal fossa can assist in diagnosing in utero absence of the other kidney. In fact, unilateral renal agenesis can cause compensatory hypertrophy of the contralateral kidney.

As previously mentioned, the adrenal gland usually occupies the renal fossa, making the diagnosis of renal agenesis difficult in many cases. In order to differentiate the adrenal gland from the kidney could be helpful to check its shape and ultrasound appearance: adrenal glands are smaller and oblong, and (in contrast to the renal medulla), the adrenal medulla is hyperechoic rather than hypoechoic. Finally, the renal pelvis cannot be visualized. Prior to a definite diagnosis of unilateral kidney agenesis, care should be taken to rule out the more frequent presence of an ectopic kidney (or of renal hypoplasia). The careful observation of the fetal pelvis, and the examination of renal vascularization could help to detect a pelvic kidney and its artery. Crossed ectopia is another condition that has to be ruled out when an empty renal loggia is found on the scan. The observation of the contralateral kidney, the evaluation of its morphology and the observation of its vascularization by color Doppler could be helpful to define the presence of two kidneys on the same side.

The finding of a dysplastic or ectopic kidney should encourage a detailed examination of the contralateral renal fossa, considering the association with URA. Similarly, the URA has to be suspected in case of other urinary tract anomalies (e.g. reflux, urinary tract obstruction, etc). The commonly associated genital abnormalities are usually not visible by ultrasound; therefore they cannot be used as indirect signs of renal agenesis. Even though fetal kidneys can be recognized by ultrasound in the first trimester,¹⁷ this anomaly is usually detected at the second trimester ultrasound anomaly scan. However, even in the second trimester, the visualization of an empty renal loggia could be missed, especially considering that the adrenal gland could be erroneously considered as a kidney and the absence of indirect signs raising the suspicion of this renal disease . When a renal loggia is suspected to be “empty”, the possibly associated contralateral hypertrophic kidney (often present in the third trimester), the identification of the ipsilateral “lying down” rounder adrenal gland and the careful examination of the renal vascularization by color Doppler (missing ipsilateral renal artery) usually confirm the diagnosis of URA.

If the unilateral renal agenesis is isolated, the prognosis is good. Long-term prognosis is influenced by the increased risk for the remaining kidney to develop proteinuria, hypertension and renal insufficiency.

Karyotyping is not mandatory as the association with chromosomal abnormalities is low (1%). Ultrasound investigation of the parents’ kidneys is necessary in case of unilateral agenesis, in view of the autosomal dominant inheritance pattern of the condition. Postnatally, scintigraphy should be performed to confirm the diagnosis and to assess renal function. These patients need specialist follow up to monitor their renal function, in view of the increased risk of renal functional problems, vescicoureteral reflux and hypertension.

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This article should be cited as: Paolo Volpe, Valentina De Robertis, Nicola Volpe Unilateral renal agenesis, Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology, www.isuog.org, 30th of March, 2013.

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