Renal agenesis

A number of small proteins, such as BMP-7, Wingless-Int (WNT) and fibroblast growth factor (FGF-2), are candidate molecules for metanephric mesenchyme induction. BMP-7 is produced in the right place, BMP-7 knockout leads to renal agenesis and antibodies to BMP-7 block nephrogenesis in vitro. However, it is produced by tissues that cannot induce nephrogenesis in a co-culture. This suggests that BMP-7 is necessary for most, but perhaps not the earliest, events in... 

Kashiwagi M, Chaoui R, Stallmach T, Hurlimann S, Lauper U, Hebisch G. Fetal bilateral renal agenesis, pho-comelia, and single umbilical artery associated with cocaine abuse in early pregnancy. Birth Defects Res Part A Clin Mol Teratol 2003 67 951-2. 

A fetus had an extremely hypotrophic candal body pole, aplasia of the lower spine, and complete renal agenesis diagnosed in the second trimester by ultrasound. The mother had used minoxidil solution to prevent hair loss for 4 years before and during gestation. She had also taken co-trimoxazole during the first trimester. She was not diabetic and had no history of familial genetic disorders. 

Intrauterine growth retardation and anomalies of the fetal urinary tract, such as bilateral renal agenesis or obstruction of the urethra, are associated with oligohydramnios, an abnormally low amniotic fluid volume. Increased fluid volume is known as hydramnios (also termed polyhydramnios). Conditions associated with hydramnios are as diverse as maternal diabetes mellitus, severe Rli isoimmune disease, fetal esophageal atresia, multifetal pregnancy, anencephaly, and spina bifida. 

Some authors described major anomalies of urinary organs in a high percentage of otherwise healthy children from affected households. "Foetal" and abnormal glomeruli were also observed among these children. Unfortunately no explanation exists for how severe anomalies, notably renal agenesis or double ureters, might disappear in adult life. 

Burk D and Beaudoin AR (1977) Arsenate-induced renal agenesis in Rats. Teratology 16 247 — 260. 

Sanchez, M.P., Silos-Santiago, I., Frisen, J., He, B., Lira, S.A. and Barbacid, M. (1996) Renal agenesis and the absenee of enteric neurons in mice lacking GDNF. Nature 382 IQ-Ti. 

Figure 4. Urinary and reproductive tract of a male fetal hamster taken from a dam given an intravenous dose of 20 mg/kg sodium arsenate on the 8th day of pregnancy and recovered on day 15. Note the undescended testis and the uilateral renal agenesis The adrenals are present. (About x 6).

Ferm, V. H. and Saxon, A., 1971, Amniotic fluid volume in experimentally Induced renal agenesis and anencephaly. Experientia, 27 1066-1068. 

In most cases renal agenesis can be regarded as a manifestation of a spectrum including hydronephrosis - cortical cysts (Potter type IV) - hypo-plastic/dysplastic or multicystic dysplastic kidneys - and renal agenesis depending on the time of the interaction of a disruption (e.g. obstruction). Dysplastic kidneys often vanish during life completely. 

After birth of a child with severe Potter phenotype due to bilateral agenesis or dysplasia in up to 10% unilateral agenesis or dysplasia can be found in one parent indicating a genetic basis. Empirical recurrence risks favour mostly multifactorial inheritance with a recurrence risk of about 5% after birth of a child with renal agenesis/dysplasia. In single pedigrees, autosomal dominant or X-linked mode of inheritance seems to be likely with incomplete penetrance and variable expressivity. Specific syndromes have to be ruled out (Table 3.2). 

Despite the overall small recurrence risk of renal agenesis careful evaluation of the family history and exclusion of syndromes is essential. Due to the early manifestation during embryogenesis the detection by prenatal ultrasound is reliable. 

Table 3.2. Syndromes with renal agenesis (selection)...

Renal adysplasia (hereditary renal adysplasia HRA) Anomalies of internal genitalia, occasional anomalies of anus, heart and spine Renal agenesis, hypodyspla-sia, dysplasia, ureteral and urethral anomalies AD (191830)... 

The contralateral kidney may be abnormal in up to 50% of patients (Malek et al. 1971). There is a 10% incidence of contralateral renal agenesis. In up to 70% of children with pelvic kidney there is associated VUR (Kramer and Kelalis 1984). In most cases of renal ectopy the adrenal gland is in normal position. Genital anomalies were found ranging from 15% of males to 75% of females (Thompson and Pace 1937 Downs et al. 1973). Skeletal anomalies occur in up to 50% of children, cardiovascular lesions were found in 9 out of 21 children (Malek et al. 1971) and gastrointestinal abnormalities in one-third of patients (Ritchey 1992). 

The most common associated abnormality is that of VUR (Fig. 4.6b) (Kramer and Kelalis 1984). Therefore, VCU should be performed in all of these patients. Skeletal anomalies, imperforate anus, and cardiovascular anomalies have an increased incidence (Abeshouse and Bhisitkul 1959). Patients with solitary crossed ectopy have a higher incidence of genital abnormalities, probably related to the renal agenesis (Kakei et al. 1976). 

Fig. 5.45a, b. Cystic Mullerian remnant in a girl with left renal agenesis, a VCU shows a pseudoureterocele (arrow) and a right side VUR. b US displays a cystic structure posterior to the bladder neck (arrow)... 

Sourtzis S, Damry N, Janssen F et al (1994) Ureteral quadru-plication. Pediatr Radiol 24 604-605 Stocks A, Richards D, Frentzen B et al (1996) Correlation of prenatal pelvic antero-posterior diameter with outcome in infancy. JUrol 155 1050-1052 Tressider GC, Blandy JP, Murray RS (1970) Pyelo-pelvic and uretero-ureteric reflux. B J Urol 42 728-735 Trigaux JP, Van Beers B, Delchambre F (1991) Male genital tract malformations associated with ipsilateral renal agenesis. J Clin Ultrasound 19 3-10... 

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