Renal agenesis is the congenital absence of one or both kidneys as a result of the complete failure of the kidney to form. The sequence of renalagenesis, severe oligohydramnios, amnion nodosum, flattened face, low set and floppy ears, bilateral pulmonary hypoplasia, and perinatal death was first described by Potter in 1946.

Renal agenesis is a developmental anomaly that occurs at 4 to 6 weeks of embryonic life (Kaffe et al., 1977). Normal renal embryogenesis requires that three events take place: the ureteric buds must arise bilaterally from mesonephric (wolffian) ducts; subsequently, bilateral metanephric blastema must form from mesoderm in the caudal region of the nephrogenic cord; and finally, ureteric buds must grow, contact, and invaginate the metanephric blastema, there by inducing differentiation of the blastema into two mature kidneys (Wax et al., 1994). Failure of the metanephros to develop results in complete absence of the kidney. This can be due to either nonexistence of the ureteral bud or failure of the ureteral bud to develop from the wolffian duct.

In unilateral renal agenesis, there is complete absence of the kidney on one side, with compensatory hypertrophy on the contralateral side. Most cases of unilateral renal agenesis are due to lack of induction of the metanephric blastema by the ureteral bud, but some cases of absent kidney may be due to in utero regression of a multicystic dysplastic kidney (see Chapter 78) (Mesrobian et al., 1993). In cases of unilateral renal agenesis, compensatory hypertrophy of the remaining kidney occurs prenatally (Zalel et al., 2002). This has been demonstrated by Hartshorne et al. (1991), who performed a retrospective analysis of 20 fetuses who died with unilateral renal agenesis. Total renal mass was measured and was shown to comprise 82.7% of the weight of both kidneys removed from control fetuses at the same gestational age. Had prenatal compensatory hypertrophy not occurred, the total renal masswould have been only 50% of control values (Hartshorne et al., 1991). It is of biologic interest that in unilateral renal agenesis, symmetrical hypertrophy of all nephron components occurs during prenatal life, when the placenta clears all metabolic waste products. These authors hypothesized that it is the change in renal mass, rather than abnormality in function, that triggers compensatory growth of the contralateral kidney. This may be due to an as yet uncharacterized renotropic humoral growth factor (Hartshorne et al., 1991).

The incidence of bilateral renal agenesis is 1 in 3000 livebirths (Cardwell, 1988; Droste et al., 1990) and 1 in 240 stillbirths (Whitehouse and Mountrose, 1973). A recent ultrasound study performed in 12 European countries by the EUROSCAN group demonstrated a prevalence of 95 cases of bilateral renal agenesis in 709,030 pregnancies (Weisel et al., 2005). The antenatal detection rate was 91% at a mean gestational age of 21.2 weeks. Bilateral renal agenesis is 2.5 times more common in males than in females. Bilateral renal agenesis is also more common in twins as compared with singletons. Some authors have postulated a common cause for twinning and the development of renal agenesis (Roodhooft et al., 1984). An increased incidence of bilateral renal agenesis is not associated with advanced maternal age or maternal illness.

Unilateral renal agenesis occurs in 1 in 500 to 1 in 1300 livebirths, although many cases are clinically silent (Bronshtein et al., 1995). In the EUROSCAN study, unilateral renal agenesis was found in 58 of 709,030 studied pregnancies (Weisel et al., 2005). The antenatal detection rate was 62% at a mean gestational age of 28.6 weeks. In one study, the missing kidney was nearly always the left one (Hartshorne et al., 1991), but in another study of 46 consecutive cases of unilateral renal agenesis, the right kidney was absent in 19 of 46 individuals (Cascio et al., 1999). The true incidence of unilateral agenesis is likely to be even greater because this abnormality can be asymptomatic throughout life.

The sonographic criterion for the diagnosis of bilateral renal agenesis is the presence of severe oligohydramnios or anhydramnios occurring after 14 to 16 weeks of gestation with failure to visualize the fetal urinary bladder and both kidneys (Droste et al., 1990). Prior to the 16th week of gestation, the fetal kidneys contribute relatively little to the amniotic fluid volume. After 28 weeks, premature rupture of the membranes or placental dysfunction may reduce amniotic fluid volume (Dubbins et al., 1981). The accuracy of the diagnosis of renal agenesis was addressed in one study, in which three groups of patients were analyzed (Romero et al., 1985). In the first group, 16 patients who had a positive family history of bilateral renal agenesis were studied. In the second group, an additional 3 patients were diagnosed with possible renal agenesis during a routine anatomic scan. In the last group, 30 patients were studied who had a previously abnormal level 1 scan that was highly suspicious for renal agenesis. In the overall study, 19 truly affected fetuses were present and of these 18 were correctly diagnosed. Seven cases were correctly diagnosed at <24 weeks of gestation. One case was a false-negative due to difficulty in imaging the kidneys at 36 weeks of gestation in a fetus with massive hydrocephaly and oligohydramnios. There were no false-positive diagnoses. In the 19 affected fetuses, no bladder was visualized in 18 of them. All 19 fetuses had oligohydramnios. These authors concluded that an absent fetal bladder diagnosed after 16 weeks of gestation should prompt further investigation for bilateral renal agenesis (Romero et al., 1985). This study demonstrated that sonographic diagnosis of renal agenesis was highly accurate in the second or third trimester (Table 86-1). Figure 86-1 demonstrates the sonographic findings in a case of unilateral renal agenesis.

Other reports of false-negative diagnoses in cases of bilateral renal agenesis have been attributed to the sonographic misidentification of apparently enlarged fetal adrenal glands as fetal kidneys. To answer the question about whether the adrenals were really enlarged, autopsy records were reviewed from 11 affected fetuses with bilateral renal agenesis. These authors compared normal values on 240 fetuses at the same gestational age. They established regression curves for adrenal weights versus foot and crown-to-rump length as an indicator of gestational age. The adrenal weights from the 11 patients with bilateral renal agenesis were all within the normal limits. Therefore, these authors concluded that adrenal hypertrophy was not a common finding in renal agenesis and that the false-negative diagnosis of renal agenesis was due to a change in the normal adrenal shape rather than an increase in adrenal mass (Figure 86-2) (Droste et al., 1990). In approximately 10% of patients with unilateral renal agenesis, the ipsilateral adrenal gland is also absent (Fortune 1927; Ashley and Mostofi, 1960).

First trimester diagnosis of bilateral renal agenesis is complicated by the fact that at that point in gestation, amniotic fluid volume is not significantly reduced. Bronshtein et al. (1994) identified 9 of 13,252 fetuses with bilateral renal agenesis by transvaginal sonography between 12 and 18 weeks of gestation. The fetal kidneys can be visualized from 10 weeks of gestation by transvaginal sonography, and they appear as bilateral echogenic masses with the same density as fetal lungs.

In contrast, the adrenal glands are relatively hypoechogenic. Diagnosis of renal agenesis consists of demonstration of oval bilateral hypoechogenic masses in the renal bed interpreted as adrenal glands. In this study, one false-positive diagnosis was made in a fetus with hypoplastic kidneys due to trisomy 22. These authors noted that the early second trimester sonographic findings in fetuses with bilateral renal agenesis consisted of three different presentations: (1) absence of any masses in the fetal flanks without sonographic evidence of ectopic kidneys, (2) the presence of bilateral hypoechogenic masses in the fetal flanks with no sonographic evidence of a fetal bladder and positive evidence of oligohydramnios at <17 weeks of gestation, and (3) bilateral hypoechogenic masses demonstrated in the fetal flanks with a small bladder present and a normal amount of amniotic fluid (Bronshtein et al., 1994).

Because oligohydramnios can impair visualization of the fetal kidneys and bladder, color Doppler sonography is recommended as an adjunct to the diagnosis of bilateral renal agenesis (Figure 86-3) (Sepulveda et al., 1998). In one study of 33 consecutive second trimester pregnancies complicated by severe oligohydramnios, high-resolution color Doppler ultrasonography was used to establish the presence or absence of renal arteries. The results showed that neither renal artery was visualized in eight fetuses; postmortem examination confirmed bilateral renal agenesis in seven fetuses and unilateral renal agenesis with a contralateral atrophic multicystic kidney in one fetus. In three cases, only one renal artery was visualized; postmortem examination confirmed unilateral renal agenesis in two fetuses and bilateral multicystic dysplastic kidneys in one fetus. When both renal arteries were identified prenatally (22 cases), postnatal or postmortem evaluation confirmed the presence of both kidneys (Sepulveda et al., 1995). Nomograms exist that predict the location of the renal arteries (distance from the bifurcation of the iliac arteries), using the fetal femur length as a reference (DeVore, 1995). In cases in which uncertainty remains after ultrasound, MRI is a useful adjunct to identify fetal kidneys or confirm unilateral or bilateral renal agenesis.