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Postnatal investigation of fetal renal disease
Seminars in Fetal & Neonatal Medicine (2008) 13, 133e141
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/siny
Postnatal investigation of fetal renal disease Rose de Bruyn*, Stephen D. Marks Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK
KEYWORDS Antenatal; Fetal; Investigation; Renal
Summary Following the introduction of routine prenatal scanning, and more recently detailed anomaly scans, antenatal ultrasound (US) diagnosis of fetal renal tract abnormalities has become well established. Prenatal detection has resulted in a group of asymptomatic infants becoming patients in the last two decades. These infants are referred for paediatric (general, urological and nephrological) consultations, radiological imaging and monitoring. The urgency with which to undertake imaging depends on the suspected antenatal diagnosis and clinical scenario, with bilateral hydronephrosis, posterior urethral valves and complicated duplex systems taking a high priority. Treatment is mainly preventive and relies on close follow-up and timely intervention. US remains the main imaging modality of choice postnatally; together with nuclear medicine, it gives a powerful combination of both anatomy and function. However, magnetic resonance urography may have increasing importance in becoming the investigation of choice of the future for more complex cases. ª 2007 Elsevier Ltd. All rights reserved.
Premature and term neonatal adaptation to extrauterine survival depends on the immature kidney maintaining normal homeostasis after the completion of nephrogenesis by 36 weeks gestation. Both renal blood flow and function are markedly reduced at birth, with premature and term neonatal glomerular filtration rates of 5e12 ml/min per 1.73 m2. The neonatal kidney has therefore a limited functional reserve and may be overwhelmed by common neonatal stresses, especially if there is fetal renal disease. Nuclear medicine imaging is generally delayed until after 3 months of age, though if there is a clinical question regarding a nonfunctioning kidney, functional imaging may be carried out earlier.
* Corresponding author. Fax: þ44 (0) 20 7829 8665. E-mail address: [email protected] (R. de Bruyn).
Imaging techniques Infants with prenatally diagnosed renal tract anomalies are often asymptomatic and over-investigation is unwarranted. The objectives of imaging are: (1) to confirm the prenatal findings; (2) to make a diagnosis or suggest a differential diagnosis; and (3) to evaluate the relative renal function in relation to the diagnosis. The speed required to undertake imaging investigations depends ultimately on the diagnosis, with inference from an essential and thorough history of the degree of dilatation antenatally according to the gestational age. With unilateral renal abnormalities, there is no urgency when the contralateral kidney and bladder are normal. In bilateral hydroureteronephrosis, imaging soon after birth is recommended. The main postnatal imaging modalities of US, together with micturating cystourethrogram (MCU), go a long way towards satisfying the first two objectives, while the third objective (i.e. evaluation of renal function) may be undertaken at a later stage.
1744-165X/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2007.10.008
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Ultrasound imaging The use of accurate antenatal history and US findings, together with postnatal US, is fundamentally important for guiding further imaging. US is safe, quick, cheap, and can be repeated. A complete examination must include images of the bladder, particularly the bladder wall thickness and presence of dilated lower ureters in male infants, and ureterocoeles in suspected duplex. In the normal neonate, there is relative dehydration with reduced urine output during the first 24e48 h, so that with unilateral hydronephrosis the US should not be undertaken before 72 h after delivery. Some institutions would repeat an US with normal or minimal dilatation on the first postnatal US to confirm normality. It must be remembered that in the anuric infant, US may fail to show hydronephrosis, even in the presence of an obstruction, such as posterior urethral valves. Prone views of the kidneys are essential for accurate measurements, particularly the renal length and measurement of the renal pelvis in transverse diameter for follow up. Resistive indices have not been shown to be either reliably accurate or to add prognostic value (particularly in the dilated kidney) and are not routinely used. The normal appearance of the neonatal kidney can be recognised (Fig. 1).
Micturating cystourethrogram The MCU is the investigation of choice for the lower urinary tract (i.e. ureters, bladder and urethra). It requires bladder catheterisation or insertion of a suprapubic catheter with the injection of a contrast agent. Indications include any suspicion of urethral pathology in boys, a thick-walled bladder or ureteric dilatation. MCU can also identify the
R. de Bruyn, S.D. Marks presence of vesicoureteric reflux (VUR). Anterior urethral valves are extremely rare in female infants and so most centres would preferably undertake a direct isotope cystogram in girls due to the lower radiation burden.
Dynamic renal scan The preferred isotope in the infant is mercaptoacetyltriglycine (99mTc-MAG3). The radiotracer is injected intravenously and extracted from the blood by proximal tubules. It passes freely into the tubular lumen and into the bladder. Major indications for the investigation include a dilated renal tract. Estimation of differential renal function (DRF) and drainage of the urinary tract is possible with this procedure. In the newborn, renal immaturity and the relatively large extravascular space dictate the use of 99mTc-MAG3. This is because this isotope remains in the blood pool rather than being distributed freely into the extravascular space, as does 99mTc-DTPA, which has a lower renal extraction rate than 99mTc-MAG3.
Static renal scan 99m
Tc-dimercaptosuccinic acid (99mTc-DMSA) binds to the proximal convoluted tubules after intravenous injection; this ‘fixing’ results in stable images over many hours. The detection of focal parenchymal abnormalities is the main indication for a static renal scan. In renal failure and/or bilateral dilatation, 99mTc-DMSA has proved essential in distinguishing between two equally affected kidneys or marked asymmetrical renal function. In this clinical setting there is no minimum age to undertake a 99mTc-DMSA scan.1 The quality of the dynamic and static isotope scan improves with renal maturation. The timing of the scan should be adjusted for the particular clinical situation. Relatively poor function does not imply irreversible damage and no long-term management should be planned on these results. Instead, the scan should be repeated either when the infant is older (over 3 months of age) or following treatment.
Intravenous urogram There is no indication for an intravenous urogram (IVU) in the neonatal period. An IVU requires the injection of a contrast agent, which should have a low osmotic load and low sodium content to avoid complications. An IVU in the neonatal period may aggravate renal venous thrombosis (RVT) or medullary necrosis. Even in normal neonates, an IVU may fail to outline the kidneys, especially in the first 48 h after birth.
Magnetic resonance imaging
Figure 1 Normal neonatal kidney. Longitudinal sonogram of the right kidney in a normal neonate. The medullae are hypoechoeic and regularly arranged around the central collecting system. The cortex is thin and relatively hyperechoeic. Notice the easily visible hypoechoeic adrenal gland above the kidney.
Magnetic resonance imaging (MRI) urography can be undertaken at any age; T2-weighted images are independent of renal function and provide images where water is readily detected. Thus, in the presence of hydronephrosis, the anatomy is outlined. However, in the vast majority of cases, US provides all the necessary information.
Postnatal investigation of fetal renal disease In the unusual, complicated duplex kidney or ectopic kidney, the full potential of MRI is yet to be explored.2 In the infant in renal failure, caution should be taken in utilising contrast-enhanced MRI because of the reported incidence of nephrogenic systemic fibrosis with gadolinium.3,4
Use of imaging techniques Prenatal US diagnosis of a renal tract abnormality identifies a heterogeneous group of conditions.5 These can be divided into three distinct entities (although they may coexist together) of structural, parenchymal and dilating anomalies with increasing accuracy of US. The major division occurs between bilateral abnormalities and unilateral abnormalities with a contralateral normal kidney and bladder. The former requires urgent imaging and management, while, except for obstructed duplex systems, unilateral abnormalities lack urgency.
Dilating abnormalities Table 1 provides a summary of the differential diagnosis of dilating abnormalities.
Unilateral renal pelvic dilatation The commonest abnormality in general obstetric practice is mild renal pelvic dilatation with an incidence of 0.5e5%, which upon postnatal US is found to be normal or with only mild dilatation.6 Screening programmes therefore induce parental anxiety by detecting fetuses who have no associated renal abnormality. Infants referred for postnatal US are those who, at their 18e20 weeks scan, are found to have a renal pelvic diameter of 5 mm or more, which either enlarges or remains static during pregnancy. Some would also include those with a measure of 8 mm at 8 months (or 1 mm per month of gestation as a rough guide). There is no test
Table 1
Differential diagnosis of dilating abnormalities
Unilateral
Bilateral
RPD/‘intermittent hydronephrosis’ VUR Megaureter (VUR obstruction) PUJ obstruction Complicated duplex kidney, i.e. obstructed upper moiety with ureterocoele and/or refluxing lower moiety
RPD/‘intermittent hydronephrosis’ VUR Megaureter (VUR obstruction) PUJ obstruction Complicated duplex kidneys
Bladder outlet pathology, e.g. PUV with uni/bilateral upper tract dilatation or neurogenic bladder RPD, renal pelvic dilatation; VUR, vesico-ureteric reflux; PUJ, pelvi-ureteric junction; PUV, posterior urethral valves.
135 available at present that will predict which kidney with a prenatal diagnosis of renal pelvic dilatation (RPD) will deteriorate. Postnatal US should be undertaken with the neonate well hydrated and should assess pelvicalyceal dilatation and measure the widest transverse diameter of the pelvis in the prone position (AP renal pelvis measurement). The US should also confirm that there is no dilated ureter or duplex system and that the bladder and contralateral kidney are structurally normal. The presence of a visible ureter on US is generally considered to be abnormal. Clinicians should note that poorer prognostic signs include US evidence of cortical thinning, cortical cysts, parenchymal abnormalities, AP renal pelvis >20 mm, marked ureteric dilatation, ureterocoeles, dilated posterior urethra and thickened bladder wall. There was an improvement in 98% of children with grades 1e2 hydronephrosis (anterior posterior pelvic diameter (APPD) <12 mm equivalent to Society of Fetal Urology grades 1e2) in a meta-analysis of 25 articles strongly suggesting the benign nature of a mild degree of pelviectasis, which is self-limiting with resolution or improvement.7 However, there is more variability with severe hydronephrosis (APPD >12 mm equivalent to Society of Fetal Urology grades 3e4). Thus, comprehensive postnatal diagnostic management was suggested by another recent meta-analysis, where there was also a significant risk of postnatal pathology with moderate and severe antenatal hydronephrosis.8 However, moderate antenatal renal pelvic dilation (5e15 mm), which suggests VUR, is not known to predict renal scarring.9
Normal postnatal US or mild dilatation With such findings, the questions arises whether the kidney is normal. VUR may be present even with a normal postnatal US. There is little published literature on the relevance of missing VUR. Various studies have shown that a normal postnatal US does not exclude VUR. However, if one considers only grade IV or V VUR, then the sensitivity of US is much higher: one study showed only 17% of kidneys with grade IV-V VUR in boys were normal on US.10 However, the other problem is that a normal US does not mean a normal kidney. Different studies have shown reduced DRF of between 30% and 50%.11e13 One report suggests that if a urinary tract infection (UTI) occurs in this group, then the frequency of an abnormal kidney is increased. Publications suggest that an MCU is not required in children who present with a proven UTI and have an abnormal US and 99mTc-DMSA scan.14 Such results preclude any dogmatic postnatal imaging protocol, but suggest a conservative imaging approach. After a normal or near normal US one approach is simply to advise of urinary surveillance should the infant become unwell with prompt diagnosis and treatment of UTI and consider commencing these infants on prophylactic antibiotics. Another alternative is to investigate with a 99mTc-DMSA scan and only if this is abnormal proceed with an MCU. The aggressive approach of undertaking MCU and 99mTc-DMSA scans on all such infants is less common. Until results of prospective studies are available, postnatal imaging will depend on the philosophy of the paediatrician rather than on existing evidence (Fig. 2).
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Figure 2 Normal and abnormal kidney with vesicoureteric reflux (VUR) in the same infant. (a) Longitudinal sonogram of the right kidney. The renal parenchyma is hyperechoeic and there is dilatation of the renal pelvis. (b) Prone longitudinal scan of the left kidney. There is a thick rim of renal parenchyma and no dilatation of the collecting system. (c) Transverse sonogram of the bladder in the same infant showing a dilated right ureter. (d) Micturating cystourethrogram in the same infant showing VUR into a dilated right renal collecting system and pelvis, and reflux on the left into a much less dilated collecting system. The urethra was normal. (e) Tc99m-dimercaptosuccinic acid (Tc99m-DMSA) scan on the same infant showing reduced function on the right and normal uptake on the left.
Renal pelvic dilatation RPD, often termed pelviureteric junction (PUJ/UPJ), obstruction can be defined postnatally by US demonstrating calyceal dilatation plus a dilated renal pelvis greater than 10e15 mm in its antero-posterior (AP) diameter with no evidence of a dilated ureter in usually asymptomatic infants. The mere presence of isolated calyceal and renal pelvic dilatation does not necessarily imply an obstruction that requires surgery (Fig. 3). If US demonstrates unilateral calyceal and RPD generally over 15 mm, the child will require a diuretic 99mTc-MAG3 renogram. Mild RPD <15 mm can be simply followed with US. 99m Tc-MAG3 renograms can be undertaken at about 8e 12 weeks of age in most cases, but with severe dilatation (>40 mm), the first study can be undertaken earlier. Follow-up should be with an US and diuretic 99mTc-MAG3 at 6 and at 12 months, if the dilatation is <40 mm and differential renal function is moderate to good (30e50%). If the dilatation and function are stable, then US at 2 years, and US plus diuretic 99mTc-MAG3 at 5 years, could be undertaken. With more marked dilatation or reduced DRF, then follow-up should be more frequent. Long-term follow-up in all cases is strongly recommended. There is no role for
Figure 3 Renal pelvic dilatation and dilated calyces. Transverse sonogram on a markedly dilated right kidney collecting system. The pelvis is measured in the prone transverse position. There is a thin rim of renal cortex and dilated calyces.
Postnatal investigation of fetal renal disease an MCU in those children who have dilatation without a dilated ureter.
Bilateral renal pelvic dilatation There is more uncertainty about the management of bilateral RPD than unilateral RPD. How to interpret the results of US and diuretic 99mTc-MAG3 is also difficult. The investigative protocol is the same as unilateral RPD, but with closer monitoring of both examinations and adding an MCU. Until more long-term data and natural history becomes available, no rigid approach can be recommended.
Megaureter Megaureter reflects a dilated ureter, where there may or may not be VUR, and kidney function is usually preserved. Dilatation of the lower ureter is usually more marked than the dilatation of the calyces and the renal pelvis. The imaging protocol is similar to that of RPD, with addition of an MCU to document whether the dilated ureter is refluxing
137 or ‘obstructed’. It is important to exclude a small ureterocele or other bladder abnormality on the US. With a suspected neuropathic bladder with a thick-walled bladder, a spinal US within the first 3 months is useful in excluding obvious spinal cord pathology.
Duplex kidney Duplex kidneys, which are detected prenatally, are generally those that are complicated and show dilatation of one or both moieties. Uncomplicated duplex kidneys, which are neither dilated nor obstructed, are generally not detected by prenatal US and are probably variations of normal. With complete duplication, US will demonstrate two moieties. The upper moiety may be normal or dysplastic or obstructed by a ureterocele. In the latter, the draining ureter will be dilated with an obstructing ureterocele (Fig. 4). The appearances of a duplex kidney are easier to see using 99mTc-DMSA, but may be recognised using 99mTcMAG3. However, the benefit of the latter will also permit assessment of drainage and/or VUR. With both dysplasia
Figure 4 Obstructed duplex. (a) Longitudinal scan of the left kidney. This shows an obstructed duplex in the upper pole of the kidney. (b) Longitudinal sonogram of the right flank in the same infant, showing a dilated left ureter leading into a ureterocele in the bladder. (c) 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renogram on the same patient showing a large defect in the upper pole of the right kidney. The right lower moiety functions and drains normally.
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and a ureterocele of the upper moiety, the appearance will depend on the degree of function. This may vary from good function to virtually a non-functioning upper moiety. With very poor function, the upper pole may appear flat medially on 99mTc-DMSA, while on 99mTc-MAG3 it may not be visualised. With a ureterocele using 99mTc-MAG3, early images will show the functional impairment and late images will show the dilated ureter. If a dilated ureter behind the bladder is found with or without a ureterocoele on US, then an MCU is indicated. US is excellent at visualising a ureterocoele in the bladder. When performing an MCU, early filling images of the bladder containing little contrast are important so that a small ureterocoele is not obscured by contrast. VUR, if present, occurs into the lower moiety. The exact anatomy may not be clear from the US of complicated duplex kidney(s) with severe hydronephrosis; isotope studies are also required, especially if there is bilateral hydronephrosis. In this clinical setting, the role of MRI may be important.
Parenchymal abnormalities Multicystic dysplastic kidney Multicystic dysplastic kidney (MCDK) should not be confused with the cystic dysplastic kidney or renal dysplasia. It is a non-hereditary cystic disorder due to failure of the ureteric bud to penetrate the metanephric mesoderm. In MCDK, there is no normal overall structural pattern to the kidney, which is always non-functioning, and there are cysts of varying sizes. The characteristic feature of a MCDK is that there is an atretic ureter. Although pathologists may consider MCDK and cystic dysplasia as two ends of a spectrum, on imaging they appear as two separate conditions. The commonest presentation is via prenatal US. MCDK is more common in males, they vary in size and involution with time is common (even intra-uterine). The larger MCDK >6 cm are the ones that may not involute. There have been a few case reports of the development of either hypertension or malignancy, but a recent series showed no hypertension, significant proteinuria, or malignancy in 165 patients, though two developed PUJ obstruction in the contralateral kidney.15 Indications for surgery include a large mass compromising respiration or feeding, or an enlarging mass. MCDK is usually unilateral and if bilateral is incompatible with life. The prognosis depends on the function of the contralateral kidney, in which there is a high association of abnormalities (30%), usually PUJ obstruction or ureteric stenosis. On US, there are a spectrum of appearances from a small single cyst to a large mass containing multiple, usually anechoic, cysts of varying sizes often with a dominant large cyst situated peripherally (Fig. 5). There is no identifiable renal parenchyma, which may help distinguish a MCDK from a severe PUJ with hydronephrosis. Occasionally, an ureterocoele may be found in the bladder. On radioisotope studies, there is no function of the MCDK. Further radioisotope imaging is indicated if the MCDK is ‘complicated’ by an abnormality detected in the contralateral kidney. The contralateral kidney requires a 99mTc-MAG3 to assess drainage, especially if the US has
Figure 5 Multicystic dysplastic kidney (MCDK). Longitudinal sonogram of the right MCDK. Multiple cysts of varying sizes occupy the whole of the kidney. This kidney was non-functioning on nuclear medicine imaging.
detected a dilated renal pelvis. MCU is not indicated unless the US reveals a dilated ureter or an abnormal bladder and/ or a contralateral kidney.
Echogenic neonatal kidneys The term ‘echogenic kidneys’ (hyperechogenic or hyperechoic or ‘bright’) is used to describe a heterogeneous group of conditions characterised by renal echogenicity greater that that of the liver or the spleen on US. US is sensitive but is non-specific. Renal biopsy and histology remain the ‘gold standard’ but it is seldom employed in neonates. If a fetus is aborted or a neonate dies, then the family should be strongly advised to seek a post-mortem in order to obtain histology. The aim postnatally is to differentiate between different genetic conditions, such as autosomal recessive and dominant polycystic kidney disease (ARPKD and ADPKD) and renal dysplasia, from conditions acquired perinatally (e.g. renal venous thrombosis or nephrocalcinosis). The differential diagnosis of the abnormally echogenic kidney is based primarily on the size of the kidneys and the clinical presentation but the site (e.g. cortical or medullary), of increased echogenicity must also be taken into account.16 In the normal neonate, the cortex is more echogenic than the liver or spleen and this is related to the dense packing of glomeruli. The kidney is normal in size and this ‘physiological’ increased echogenicity disappears by about 3 months.
Large echogenic kidneys The aetiology includes a number of genetic and sporadic conditions and the antenatal differential diagnosis is large
Postnatal investigation of fetal renal disease with many of these infants aborted. Nevertheless, the final diagnosis requires information about clinical presentation, renal status, prenatal scans, family history, and US results of parental and sibling scans.17
Autosomal recessive polycystic renal disease With recessive inheritance, the parents are always unaffected which is important to remember when scanning families.18 All children develop hepatic and renal involvement. On US, both kidneys are always equally involved and markedly enlarged, measuring above the 95th centile for age in early infancy. The characteristic appearance is that of a globally hyper-reflective kidney from the acoustic enhancement behind the numerous small ectatic cysts, especially when new high-frequency US probes are used (Fig. 6). Occasionally, cysts <2 cm may be found, especially as the child grows. It is important to remember that ARPKD has a spectrum of appearances from severely affected kidneys and liver to a subtler increased echogenicity affecting mainly the medullae. Although there may be a
139 characteristic US appearance in the neonatal period, there are reports of changing appearance with age resulting in the original diagnosis being questioned. An IVU may be undertaken at about 6e12 months of age, which can show a streaky nephrogram as contrast clears in the dilated ectatic collecting ducts. The 99mTc-DMSA scan shows multiple focal defects, which in this clinical context are typical; this examination should be undertaken at the time of the IVU. The US appearance is not always specific; ADPKD, dysplasia and glomerulocystic disease may have similar appearances. Glomerulocystic disease is a histopathological description with dilatation of Bowman’s spaces and mildly enlarged kidneys, which are hyperechoic with very poor corticomedullary differentiation and cortical cysts. This condition can be sporadic or familial and is associated with genetic conditions and syndromes, including renal cysts and diabetes, oro-facial-digital, Jeune and Zellweger syndromes. Hepatosplenomegaly and portal hypertension is not a feature in the neonate and the spectrum of hepatic abnormalities may be subtle on neonatal US. The areas of cystic bile duct dilatation are easiest seen on US (Fig. 7). In later childhood, the liver is enlarged with increased echogenicity in the periportal region from bile duct proliferation and fibrosis. Single, or more usually multiple, cysts communicating and closely related biliary tree together with biliary ectasia may be present. A radionuclide 99mTc-hepatic iminodiacetic acid (HIDA) scan shows an enlarged left lobe of the liver in addition to stagnation and delayed clearance from the biliary tract and is best seen after 1 year of age.
Autosomal dominant polycystic kidney disease The presence of a family history usually makes the diagnosis of ADPKD, so if clinically suspected both parents
Figure 6 Autosomal recessive polycystic kidney disease (ARPKD) in a neonate. (a) Longitudinal sonogram of the right kidney in an infant with ARPKD. The kidney is markedly enlarged containing multiple small cysts. (b) Magnetic resonance imaging scan on the same infant showing the bilateral and symmetrical involvement of both kidneys containing multiple small cysts. Notice the dilated ectatic biliary tree.
Figure 7 Liver changes in autosomal recessive polycystic kidney disease. Longitudinal sonogram of the liver of the same infant in Fig. 6. There are multiple dilated ectatic ducts seen in the right lobe. These can be easily differentiated from vessels with the use of Doppler.
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R. de Bruyn, S.D. Marks spleen are rarely seen in paediatric patients. Congenital hepatic fibrosis is generally associated with ARPKD, but some rare cases have been described in association with ADPKD. On US, the large echogenic kidney seen in ARPKD can be indistinguishable from ADPKD in the early neonatal period and before the larger cysts have begun to appear. To date the only reported difference in imaging is on the IVU where puddling contrast has been described.20
Congenital nephrotic syndrome In infants and children who present with features of congenital nephrotic syndrome, the kidneys are enlarged and globally hyperechoic but US will not distinguish between the various forms.
Other conditions Congenital infections, such as HIV and TORCH infections, are sometimes associated with inflammatory infiltrates resulting in large, ‘bright’ kidneys. The severe form of neonatal primary hyperoxaluria is extremely rare and associated with end stage renal failure. The kidneys are moderately enlarged and highly echogenic, although their appearance is distinct from that of classical nephrocalcinosis.
Small echogenic kidneys
Figure 8 Autosomal dominant polycystic kidney disease (ADPKD) in a neonate. (a) Postnatal longitudinal sonogram of the right kidney in a neonate. There was a family history of ADPKD and the neonate had been detected antenatally as having echogenic kidneys. The US showed normal size echogenic kidneys and on the right a small visible cyst (between þ) was detected. (b) The same infant 6 months later had much larger visible cysts (between markers) in keeping with ADPKD.
require renal US themselves. Rarely, ADPKD may present with large echogenic kidneys in fetal or neonatal life (Fig. 8). The kidneys in children with ADPKD usually have a normal parenchyma but contain visible macroscopic cysts. In infants with highly cystic kidneys and no family history, the diagnosis of tuberous sclerosis must be actively excluded with a cranial MRI and echocardiogram. ADPKD is a systemic disease with both renal and extrarenal manifestations. In PKD1 families, 64% of affected children under the age of 10 years will have cysts, while 90% between the ages of 10 and 19 years will have cysts.19 However, the diagnosis cannot be excluded by normal US appearances until the individual is 35 years old. Extrarenal manifestations, such as cysts in the liver, pancreas or
Dysplasia is a generic term for a small, highly reflective, poorly functioning kidney without establishing histology by an invasive renal biopsy. These dysplastic kidneys usually function to some degree, albeit poorly.21 The first-line investigation is US which will show a cystic/dysplastic kidney less than the 50th centile, with loss of the normal corticomedullary differentiation, and hyper-reflective, with a variable number of usually small, subcapsular cysts. VUR is common. They are known to be associated with obstruction to the urinary tract such as posterior urethral valves. Dilatation of the collecting system is only seen with severe VUR. The 99mTc-DMSA scan shows reduced function if unilateral or poor visualisation of the kidneys if bilateral. Frequently, there are focal defects in the kidney that can mimic the scar of UTI. Careful examination of the whole renal tract is required, as dysplasia is often seen in association with other congenital malformations of the kidney (Fig. 9).
Structural abnormalities Crossed fused ectopia, pelvic and absent kidneys may all be detected antenatally. Horseshoe kidneys are less reliably diagnosed with US as are the uncomplicated duplex kidneys.
Conclusion Prenatal US has allowed improved early management of certain conditions, particularly the obstructive uropathies. However, the majority of infants identified prenatally are
Postnatal investigation of fetal renal disease
Figure 9 Cystic dysplasia. This infant was detected antenatally with echogenic kidneys. On postnatal US, the kidneys were small and globally hyperechoeic with no corticomedullary differentiation. There were multiple small cysts seen subcortically, which are typical of those seen in cystic dysplasia.
asymptomatic. Imaging and management remains controversial with very few long-term natural history studies. Imaging principles should be the least invasive investigations using the lowest radiation burden with no unnecessary investigations.
References 1. Strauss J, Daniel SS, James LS. Post natal adjustments in renal function. Pediatrics 1981;68:802e7.
141 2. Borthne A, Nordshus T, Reiseter T, et al. MR urography: the future gold standard in paediatric urogenital imaging? Pediatr Radiol 1999;29:694e701. 3. Broome DR, Girguis MS, Baron PW, et al. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007;188:586e92. 4. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17:2359e62. 5. de Bruyn R, Gordon I. Diagnostic imaging of the neonatal urinary tract. In: Freeman NV, Burge DM, Griffiths DM, Malone PS, editors. Surgery of the new-born. London: Churchill Livingstone; 1994. p. 671e82. 6. Jaswon MS, Dibble L, Puri S, et al. Prospective study of outcome in antenatally diagnosed renal pelvic dilatation. Arch Dis Child Fetal Neonat Ed 1999;80:F135e8. 7. Sidhu G, Beyene J, Rosenblum ND. Outcome of isolated antenatal hydronephrosis: a systematic review and meta-analysis. Pediatr Nephrol 2006;21:218e24. 8. Lee RS, Cendron M, Kinnamon DD, et al. Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis. Pediatrics 2006;118:586e93. 9. Plant ND, Hornung RJ, Coulthard MG, et al. Does antenatal pelvic dilation predict renal scarring? Arch Dis Child Fetal Neonatal Ed 2005;90:F339e40. 10. Tibballs JM, de Bruyn R. Primary vesicoureteric refluxdhow useful is postnatal ultrasound? Arch Dis Child 1996;75:444e7. 11. Crabbe DCG, Thomas DFM, Gordon AC, et al. Use of Tc99m DMSA to show patterns of renal damage associated with prenatally detected vesicoureteral reflux. J Urol 1992;148:1239e41. 12. Elder JS. Importance of antenatal diagnosis of vesicoureteral reflux. J Urol 1992;148:1750e4. 13. Sheridan M, Jewkes F, Gough DCS. Reflux nephropathy in the first year of lifedthe role of infection. Pediatr Surg Int 1991; 6:214e7. 14. Stokland E, Hansson S, Jodal U. An alternative approach to investigation of children with urinary tract infection. Pediatr Radiol 2001;31(Suppl 1):S32. 15. Aslam M, Watson AR. Trent & Anglia MCDK Study Group. Unilateral multicystic dysplastic kidney: long term outcomes. Arch Dis Child 2006;91:820e3. 16. Slovis TL, Bernstein J, Gruskin A. Hyperechoic kidneys in the newborn and young infant. Pediatr Nephrol 1993;7:294e302. 17. de Bruyn R, Gordon I. The imaging of cystic renal disease in children. Arch Dis Child 2000;5:401e7. 18. Kaplan BS, Fay FM, Shah VM, et al. Autosomal recessive polycystic kidney disease. Pediatr Nephol 1989;3:43e9. 19. Bear JC, Parfrey PS, Morgan JM, et al. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet 1992;43:548e53. 20. Hayden CK, Swischuk LE, Davis M, Brouhard BH. Puddling: a distinguishing feature of adult polycystic kidney disease in the neonate. Am J Roentgenol 1984;142:811e2. 21. Bernstein J. Developmental abnormalities of the renal parenchyma: renal hypoplasia and dysplasia. Pathol Annu 1968;3: 213.
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journal homepage: www.elsevier.com/locate/siny
Postnatal investigation of fetal renal disease Rose de Bruyn*, Stephen D. Marks Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK
KEYWORDS Antenatal; Fetal; Investigation; Renal
Summary Following the introduction of routine prenatal scanning, and more recently detailed anomaly scans, antenatal ultrasound (US) diagnosis of fetal renal tract abnormalities has become well established. Prenatal detection has resulted in a group of asymptomatic infants becoming patients in the last two decades. These infants are referred for paediatric (general, urological and nephrological) consultations, radiological imaging and monitoring. The urgency with which to undertake imaging depends on the suspected antenatal diagnosis and clinical scenario, with bilateral hydronephrosis, posterior urethral valves and complicated duplex systems taking a high priority. Treatment is mainly preventive and relies on close follow-up and timely intervention. US remains the main imaging modality of choice postnatally; together with nuclear medicine, it gives a powerful combination of both anatomy and function. However, magnetic resonance urography may have increasing importance in becoming the investigation of choice of the future for more complex cases. ª 2007 Elsevier Ltd. All rights reserved.
Premature and term neonatal adaptation to extrauterine survival depends on the immature kidney maintaining normal homeostasis after the completion of nephrogenesis by 36 weeks gestation. Both renal blood flow and function are markedly reduced at birth, with premature and term neonatal glomerular filtration rates of 5e12 ml/min per 1.73 m2. The neonatal kidney has therefore a limited functional reserve and may be overwhelmed by common neonatal stresses, especially if there is fetal renal disease. Nuclear medicine imaging is generally delayed until after 3 months of age, though if there is a clinical question regarding a nonfunctioning kidney, functional imaging may be carried out earlier.
* Corresponding author. Fax: þ44 (0) 20 7829 8665. E-mail address: [email protected] (R. de Bruyn).
Imaging techniques Infants with prenatally diagnosed renal tract anomalies are often asymptomatic and over-investigation is unwarranted. The objectives of imaging are: (1) to confirm the prenatal findings; (2) to make a diagnosis or suggest a differential diagnosis; and (3) to evaluate the relative renal function in relation to the diagnosis. The speed required to undertake imaging investigations depends ultimately on the diagnosis, with inference from an essential and thorough history of the degree of dilatation antenatally according to the gestational age. With unilateral renal abnormalities, there is no urgency when the contralateral kidney and bladder are normal. In bilateral hydroureteronephrosis, imaging soon after birth is recommended. The main postnatal imaging modalities of US, together with micturating cystourethrogram (MCU), go a long way towards satisfying the first two objectives, while the third objective (i.e. evaluation of renal function) may be undertaken at a later stage.
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Ultrasound imaging The use of accurate antenatal history and US findings, together with postnatal US, is fundamentally important for guiding further imaging. US is safe, quick, cheap, and can be repeated. A complete examination must include images of the bladder, particularly the bladder wall thickness and presence of dilated lower ureters in male infants, and ureterocoeles in suspected duplex. In the normal neonate, there is relative dehydration with reduced urine output during the first 24e48 h, so that with unilateral hydronephrosis the US should not be undertaken before 72 h after delivery. Some institutions would repeat an US with normal or minimal dilatation on the first postnatal US to confirm normality. It must be remembered that in the anuric infant, US may fail to show hydronephrosis, even in the presence of an obstruction, such as posterior urethral valves. Prone views of the kidneys are essential for accurate measurements, particularly the renal length and measurement of the renal pelvis in transverse diameter for follow up. Resistive indices have not been shown to be either reliably accurate or to add prognostic value (particularly in the dilated kidney) and are not routinely used. The normal appearance of the neonatal kidney can be recognised (Fig. 1).
Micturating cystourethrogram The MCU is the investigation of choice for the lower urinary tract (i.e. ureters, bladder and urethra). It requires bladder catheterisation or insertion of a suprapubic catheter with the injection of a contrast agent. Indications include any suspicion of urethral pathology in boys, a thick-walled bladder or ureteric dilatation. MCU can also identify the
R. de Bruyn, S.D. Marks presence of vesicoureteric reflux (VUR). Anterior urethral valves are extremely rare in female infants and so most centres would preferably undertake a direct isotope cystogram in girls due to the lower radiation burden.
Dynamic renal scan The preferred isotope in the infant is mercaptoacetyltriglycine (99mTc-MAG3). The radiotracer is injected intravenously and extracted from the blood by proximal tubules. It passes freely into the tubular lumen and into the bladder. Major indications for the investigation include a dilated renal tract. Estimation of differential renal function (DRF) and drainage of the urinary tract is possible with this procedure. In the newborn, renal immaturity and the relatively large extravascular space dictate the use of 99mTc-MAG3. This is because this isotope remains in the blood pool rather than being distributed freely into the extravascular space, as does 99mTc-DTPA, which has a lower renal extraction rate than 99mTc-MAG3.
Static renal scan 99m
Tc-dimercaptosuccinic acid (99mTc-DMSA) binds to the proximal convoluted tubules after intravenous injection; this ‘fixing’ results in stable images over many hours. The detection of focal parenchymal abnormalities is the main indication for a static renal scan. In renal failure and/or bilateral dilatation, 99mTc-DMSA has proved essential in distinguishing between two equally affected kidneys or marked asymmetrical renal function. In this clinical setting there is no minimum age to undertake a 99mTc-DMSA scan.1 The quality of the dynamic and static isotope scan improves with renal maturation. The timing of the scan should be adjusted for the particular clinical situation. Relatively poor function does not imply irreversible damage and no long-term management should be planned on these results. Instead, the scan should be repeated either when the infant is older (over 3 months of age) or following treatment.
Intravenous urogram There is no indication for an intravenous urogram (IVU) in the neonatal period. An IVU requires the injection of a contrast agent, which should have a low osmotic load and low sodium content to avoid complications. An IVU in the neonatal period may aggravate renal venous thrombosis (RVT) or medullary necrosis. Even in normal neonates, an IVU may fail to outline the kidneys, especially in the first 48 h after birth.
Magnetic resonance imaging
Figure 1 Normal neonatal kidney. Longitudinal sonogram of the right kidney in a normal neonate. The medullae are hypoechoeic and regularly arranged around the central collecting system. The cortex is thin and relatively hyperechoeic. Notice the easily visible hypoechoeic adrenal gland above the kidney.
Magnetic resonance imaging (MRI) urography can be undertaken at any age; T2-weighted images are independent of renal function and provide images where water is readily detected. Thus, in the presence of hydronephrosis, the anatomy is outlined. However, in the vast majority of cases, US provides all the necessary information.
Postnatal investigation of fetal renal disease In the unusual, complicated duplex kidney or ectopic kidney, the full potential of MRI is yet to be explored.2 In the infant in renal failure, caution should be taken in utilising contrast-enhanced MRI because of the reported incidence of nephrogenic systemic fibrosis with gadolinium.3,4
Use of imaging techniques Prenatal US diagnosis of a renal tract abnormality identifies a heterogeneous group of conditions.5 These can be divided into three distinct entities (although they may coexist together) of structural, parenchymal and dilating anomalies with increasing accuracy of US. The major division occurs between bilateral abnormalities and unilateral abnormalities with a contralateral normal kidney and bladder. The former requires urgent imaging and management, while, except for obstructed duplex systems, unilateral abnormalities lack urgency.
Dilating abnormalities Table 1 provides a summary of the differential diagnosis of dilating abnormalities.
Unilateral renal pelvic dilatation The commonest abnormality in general obstetric practice is mild renal pelvic dilatation with an incidence of 0.5e5%, which upon postnatal US is found to be normal or with only mild dilatation.6 Screening programmes therefore induce parental anxiety by detecting fetuses who have no associated renal abnormality. Infants referred for postnatal US are those who, at their 18e20 weeks scan, are found to have a renal pelvic diameter of 5 mm or more, which either enlarges or remains static during pregnancy. Some would also include those with a measure of 8 mm at 8 months (or 1 mm per month of gestation as a rough guide). There is no test
Table 1
Differential diagnosis of dilating abnormalities
Unilateral
Bilateral
RPD/‘intermittent hydronephrosis’ VUR Megaureter (VUR obstruction) PUJ obstruction Complicated duplex kidney, i.e. obstructed upper moiety with ureterocoele and/or refluxing lower moiety
RPD/‘intermittent hydronephrosis’ VUR Megaureter (VUR obstruction) PUJ obstruction Complicated duplex kidneys
Bladder outlet pathology, e.g. PUV with uni/bilateral upper tract dilatation or neurogenic bladder RPD, renal pelvic dilatation; VUR, vesico-ureteric reflux; PUJ, pelvi-ureteric junction; PUV, posterior urethral valves.
135 available at present that will predict which kidney with a prenatal diagnosis of renal pelvic dilatation (RPD) will deteriorate. Postnatal US should be undertaken with the neonate well hydrated and should assess pelvicalyceal dilatation and measure the widest transverse diameter of the pelvis in the prone position (AP renal pelvis measurement). The US should also confirm that there is no dilated ureter or duplex system and that the bladder and contralateral kidney are structurally normal. The presence of a visible ureter on US is generally considered to be abnormal. Clinicians should note that poorer prognostic signs include US evidence of cortical thinning, cortical cysts, parenchymal abnormalities, AP renal pelvis >20 mm, marked ureteric dilatation, ureterocoeles, dilated posterior urethra and thickened bladder wall. There was an improvement in 98% of children with grades 1e2 hydronephrosis (anterior posterior pelvic diameter (APPD) <12 mm equivalent to Society of Fetal Urology grades 1e2) in a meta-analysis of 25 articles strongly suggesting the benign nature of a mild degree of pelviectasis, which is self-limiting with resolution or improvement.7 However, there is more variability with severe hydronephrosis (APPD >12 mm equivalent to Society of Fetal Urology grades 3e4). Thus, comprehensive postnatal diagnostic management was suggested by another recent meta-analysis, where there was also a significant risk of postnatal pathology with moderate and severe antenatal hydronephrosis.8 However, moderate antenatal renal pelvic dilation (5e15 mm), which suggests VUR, is not known to predict renal scarring.9
Normal postnatal US or mild dilatation With such findings, the questions arises whether the kidney is normal. VUR may be present even with a normal postnatal US. There is little published literature on the relevance of missing VUR. Various studies have shown that a normal postnatal US does not exclude VUR. However, if one considers only grade IV or V VUR, then the sensitivity of US is much higher: one study showed only 17% of kidneys with grade IV-V VUR in boys were normal on US.10 However, the other problem is that a normal US does not mean a normal kidney. Different studies have shown reduced DRF of between 30% and 50%.11e13 One report suggests that if a urinary tract infection (UTI) occurs in this group, then the frequency of an abnormal kidney is increased. Publications suggest that an MCU is not required in children who present with a proven UTI and have an abnormal US and 99mTc-DMSA scan.14 Such results preclude any dogmatic postnatal imaging protocol, but suggest a conservative imaging approach. After a normal or near normal US one approach is simply to advise of urinary surveillance should the infant become unwell with prompt diagnosis and treatment of UTI and consider commencing these infants on prophylactic antibiotics. Another alternative is to investigate with a 99mTc-DMSA scan and only if this is abnormal proceed with an MCU. The aggressive approach of undertaking MCU and 99mTc-DMSA scans on all such infants is less common. Until results of prospective studies are available, postnatal imaging will depend on the philosophy of the paediatrician rather than on existing evidence (Fig. 2).
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Figure 2 Normal and abnormal kidney with vesicoureteric reflux (VUR) in the same infant. (a) Longitudinal sonogram of the right kidney. The renal parenchyma is hyperechoeic and there is dilatation of the renal pelvis. (b) Prone longitudinal scan of the left kidney. There is a thick rim of renal parenchyma and no dilatation of the collecting system. (c) Transverse sonogram of the bladder in the same infant showing a dilated right ureter. (d) Micturating cystourethrogram in the same infant showing VUR into a dilated right renal collecting system and pelvis, and reflux on the left into a much less dilated collecting system. The urethra was normal. (e) Tc99m-dimercaptosuccinic acid (Tc99m-DMSA) scan on the same infant showing reduced function on the right and normal uptake on the left.
Renal pelvic dilatation RPD, often termed pelviureteric junction (PUJ/UPJ), obstruction can be defined postnatally by US demonstrating calyceal dilatation plus a dilated renal pelvis greater than 10e15 mm in its antero-posterior (AP) diameter with no evidence of a dilated ureter in usually asymptomatic infants. The mere presence of isolated calyceal and renal pelvic dilatation does not necessarily imply an obstruction that requires surgery (Fig. 3). If US demonstrates unilateral calyceal and RPD generally over 15 mm, the child will require a diuretic 99mTc-MAG3 renogram. Mild RPD <15 mm can be simply followed with US. 99m Tc-MAG3 renograms can be undertaken at about 8e 12 weeks of age in most cases, but with severe dilatation (>40 mm), the first study can be undertaken earlier. Follow-up should be with an US and diuretic 99mTc-MAG3 at 6 and at 12 months, if the dilatation is <40 mm and differential renal function is moderate to good (30e50%). If the dilatation and function are stable, then US at 2 years, and US plus diuretic 99mTc-MAG3 at 5 years, could be undertaken. With more marked dilatation or reduced DRF, then follow-up should be more frequent. Long-term follow-up in all cases is strongly recommended. There is no role for
Figure 3 Renal pelvic dilatation and dilated calyces. Transverse sonogram on a markedly dilated right kidney collecting system. The pelvis is measured in the prone transverse position. There is a thin rim of renal cortex and dilated calyces.
Postnatal investigation of fetal renal disease an MCU in those children who have dilatation without a dilated ureter.
Bilateral renal pelvic dilatation There is more uncertainty about the management of bilateral RPD than unilateral RPD. How to interpret the results of US and diuretic 99mTc-MAG3 is also difficult. The investigative protocol is the same as unilateral RPD, but with closer monitoring of both examinations and adding an MCU. Until more long-term data and natural history becomes available, no rigid approach can be recommended.
Megaureter Megaureter reflects a dilated ureter, where there may or may not be VUR, and kidney function is usually preserved. Dilatation of the lower ureter is usually more marked than the dilatation of the calyces and the renal pelvis. The imaging protocol is similar to that of RPD, with addition of an MCU to document whether the dilated ureter is refluxing
137 or ‘obstructed’. It is important to exclude a small ureterocele or other bladder abnormality on the US. With a suspected neuropathic bladder with a thick-walled bladder, a spinal US within the first 3 months is useful in excluding obvious spinal cord pathology.
Duplex kidney Duplex kidneys, which are detected prenatally, are generally those that are complicated and show dilatation of one or both moieties. Uncomplicated duplex kidneys, which are neither dilated nor obstructed, are generally not detected by prenatal US and are probably variations of normal. With complete duplication, US will demonstrate two moieties. The upper moiety may be normal or dysplastic or obstructed by a ureterocele. In the latter, the draining ureter will be dilated with an obstructing ureterocele (Fig. 4). The appearances of a duplex kidney are easier to see using 99mTc-DMSA, but may be recognised using 99mTcMAG3. However, the benefit of the latter will also permit assessment of drainage and/or VUR. With both dysplasia
Figure 4 Obstructed duplex. (a) Longitudinal scan of the left kidney. This shows an obstructed duplex in the upper pole of the kidney. (b) Longitudinal sonogram of the right flank in the same infant, showing a dilated left ureter leading into a ureterocele in the bladder. (c) 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renogram on the same patient showing a large defect in the upper pole of the right kidney. The right lower moiety functions and drains normally.
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and a ureterocele of the upper moiety, the appearance will depend on the degree of function. This may vary from good function to virtually a non-functioning upper moiety. With very poor function, the upper pole may appear flat medially on 99mTc-DMSA, while on 99mTc-MAG3 it may not be visualised. With a ureterocele using 99mTc-MAG3, early images will show the functional impairment and late images will show the dilated ureter. If a dilated ureter behind the bladder is found with or without a ureterocoele on US, then an MCU is indicated. US is excellent at visualising a ureterocoele in the bladder. When performing an MCU, early filling images of the bladder containing little contrast are important so that a small ureterocoele is not obscured by contrast. VUR, if present, occurs into the lower moiety. The exact anatomy may not be clear from the US of complicated duplex kidney(s) with severe hydronephrosis; isotope studies are also required, especially if there is bilateral hydronephrosis. In this clinical setting, the role of MRI may be important.
Parenchymal abnormalities Multicystic dysplastic kidney Multicystic dysplastic kidney (MCDK) should not be confused with the cystic dysplastic kidney or renal dysplasia. It is a non-hereditary cystic disorder due to failure of the ureteric bud to penetrate the metanephric mesoderm. In MCDK, there is no normal overall structural pattern to the kidney, which is always non-functioning, and there are cysts of varying sizes. The characteristic feature of a MCDK is that there is an atretic ureter. Although pathologists may consider MCDK and cystic dysplasia as two ends of a spectrum, on imaging they appear as two separate conditions. The commonest presentation is via prenatal US. MCDK is more common in males, they vary in size and involution with time is common (even intra-uterine). The larger MCDK >6 cm are the ones that may not involute. There have been a few case reports of the development of either hypertension or malignancy, but a recent series showed no hypertension, significant proteinuria, or malignancy in 165 patients, though two developed PUJ obstruction in the contralateral kidney.15 Indications for surgery include a large mass compromising respiration or feeding, or an enlarging mass. MCDK is usually unilateral and if bilateral is incompatible with life. The prognosis depends on the function of the contralateral kidney, in which there is a high association of abnormalities (30%), usually PUJ obstruction or ureteric stenosis. On US, there are a spectrum of appearances from a small single cyst to a large mass containing multiple, usually anechoic, cysts of varying sizes often with a dominant large cyst situated peripherally (Fig. 5). There is no identifiable renal parenchyma, which may help distinguish a MCDK from a severe PUJ with hydronephrosis. Occasionally, an ureterocoele may be found in the bladder. On radioisotope studies, there is no function of the MCDK. Further radioisotope imaging is indicated if the MCDK is ‘complicated’ by an abnormality detected in the contralateral kidney. The contralateral kidney requires a 99mTc-MAG3 to assess drainage, especially if the US has
Figure 5 Multicystic dysplastic kidney (MCDK). Longitudinal sonogram of the right MCDK. Multiple cysts of varying sizes occupy the whole of the kidney. This kidney was non-functioning on nuclear medicine imaging.
detected a dilated renal pelvis. MCU is not indicated unless the US reveals a dilated ureter or an abnormal bladder and/ or a contralateral kidney.
Echogenic neonatal kidneys The term ‘echogenic kidneys’ (hyperechogenic or hyperechoic or ‘bright’) is used to describe a heterogeneous group of conditions characterised by renal echogenicity greater that that of the liver or the spleen on US. US is sensitive but is non-specific. Renal biopsy and histology remain the ‘gold standard’ but it is seldom employed in neonates. If a fetus is aborted or a neonate dies, then the family should be strongly advised to seek a post-mortem in order to obtain histology. The aim postnatally is to differentiate between different genetic conditions, such as autosomal recessive and dominant polycystic kidney disease (ARPKD and ADPKD) and renal dysplasia, from conditions acquired perinatally (e.g. renal venous thrombosis or nephrocalcinosis). The differential diagnosis of the abnormally echogenic kidney is based primarily on the size of the kidneys and the clinical presentation but the site (e.g. cortical or medullary), of increased echogenicity must also be taken into account.16 In the normal neonate, the cortex is more echogenic than the liver or spleen and this is related to the dense packing of glomeruli. The kidney is normal in size and this ‘physiological’ increased echogenicity disappears by about 3 months.
Large echogenic kidneys The aetiology includes a number of genetic and sporadic conditions and the antenatal differential diagnosis is large
Postnatal investigation of fetal renal disease with many of these infants aborted. Nevertheless, the final diagnosis requires information about clinical presentation, renal status, prenatal scans, family history, and US results of parental and sibling scans.17
Autosomal recessive polycystic renal disease With recessive inheritance, the parents are always unaffected which is important to remember when scanning families.18 All children develop hepatic and renal involvement. On US, both kidneys are always equally involved and markedly enlarged, measuring above the 95th centile for age in early infancy. The characteristic appearance is that of a globally hyper-reflective kidney from the acoustic enhancement behind the numerous small ectatic cysts, especially when new high-frequency US probes are used (Fig. 6). Occasionally, cysts <2 cm may be found, especially as the child grows. It is important to remember that ARPKD has a spectrum of appearances from severely affected kidneys and liver to a subtler increased echogenicity affecting mainly the medullae. Although there may be a
139 characteristic US appearance in the neonatal period, there are reports of changing appearance with age resulting in the original diagnosis being questioned. An IVU may be undertaken at about 6e12 months of age, which can show a streaky nephrogram as contrast clears in the dilated ectatic collecting ducts. The 99mTc-DMSA scan shows multiple focal defects, which in this clinical context are typical; this examination should be undertaken at the time of the IVU. The US appearance is not always specific; ADPKD, dysplasia and glomerulocystic disease may have similar appearances. Glomerulocystic disease is a histopathological description with dilatation of Bowman’s spaces and mildly enlarged kidneys, which are hyperechoic with very poor corticomedullary differentiation and cortical cysts. This condition can be sporadic or familial and is associated with genetic conditions and syndromes, including renal cysts and diabetes, oro-facial-digital, Jeune and Zellweger syndromes. Hepatosplenomegaly and portal hypertension is not a feature in the neonate and the spectrum of hepatic abnormalities may be subtle on neonatal US. The areas of cystic bile duct dilatation are easiest seen on US (Fig. 7). In later childhood, the liver is enlarged with increased echogenicity in the periportal region from bile duct proliferation and fibrosis. Single, or more usually multiple, cysts communicating and closely related biliary tree together with biliary ectasia may be present. A radionuclide 99mTc-hepatic iminodiacetic acid (HIDA) scan shows an enlarged left lobe of the liver in addition to stagnation and delayed clearance from the biliary tract and is best seen after 1 year of age.
Autosomal dominant polycystic kidney disease The presence of a family history usually makes the diagnosis of ADPKD, so if clinically suspected both parents
Figure 6 Autosomal recessive polycystic kidney disease (ARPKD) in a neonate. (a) Longitudinal sonogram of the right kidney in an infant with ARPKD. The kidney is markedly enlarged containing multiple small cysts. (b) Magnetic resonance imaging scan on the same infant showing the bilateral and symmetrical involvement of both kidneys containing multiple small cysts. Notice the dilated ectatic biliary tree.
Figure 7 Liver changes in autosomal recessive polycystic kidney disease. Longitudinal sonogram of the liver of the same infant in Fig. 6. There are multiple dilated ectatic ducts seen in the right lobe. These can be easily differentiated from vessels with the use of Doppler.
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R. de Bruyn, S.D. Marks spleen are rarely seen in paediatric patients. Congenital hepatic fibrosis is generally associated with ARPKD, but some rare cases have been described in association with ADPKD. On US, the large echogenic kidney seen in ARPKD can be indistinguishable from ADPKD in the early neonatal period and before the larger cysts have begun to appear. To date the only reported difference in imaging is on the IVU where puddling contrast has been described.20
Congenital nephrotic syndrome In infants and children who present with features of congenital nephrotic syndrome, the kidneys are enlarged and globally hyperechoic but US will not distinguish between the various forms.
Other conditions Congenital infections, such as HIV and TORCH infections, are sometimes associated with inflammatory infiltrates resulting in large, ‘bright’ kidneys. The severe form of neonatal primary hyperoxaluria is extremely rare and associated with end stage renal failure. The kidneys are moderately enlarged and highly echogenic, although their appearance is distinct from that of classical nephrocalcinosis.
Small echogenic kidneys
Figure 8 Autosomal dominant polycystic kidney disease (ADPKD) in a neonate. (a) Postnatal longitudinal sonogram of the right kidney in a neonate. There was a family history of ADPKD and the neonate had been detected antenatally as having echogenic kidneys. The US showed normal size echogenic kidneys and on the right a small visible cyst (between þ) was detected. (b) The same infant 6 months later had much larger visible cysts (between markers) in keeping with ADPKD.
require renal US themselves. Rarely, ADPKD may present with large echogenic kidneys in fetal or neonatal life (Fig. 8). The kidneys in children with ADPKD usually have a normal parenchyma but contain visible macroscopic cysts. In infants with highly cystic kidneys and no family history, the diagnosis of tuberous sclerosis must be actively excluded with a cranial MRI and echocardiogram. ADPKD is a systemic disease with both renal and extrarenal manifestations. In PKD1 families, 64% of affected children under the age of 10 years will have cysts, while 90% between the ages of 10 and 19 years will have cysts.19 However, the diagnosis cannot be excluded by normal US appearances until the individual is 35 years old. Extrarenal manifestations, such as cysts in the liver, pancreas or
Dysplasia is a generic term for a small, highly reflective, poorly functioning kidney without establishing histology by an invasive renal biopsy. These dysplastic kidneys usually function to some degree, albeit poorly.21 The first-line investigation is US which will show a cystic/dysplastic kidney less than the 50th centile, with loss of the normal corticomedullary differentiation, and hyper-reflective, with a variable number of usually small, subcapsular cysts. VUR is common. They are known to be associated with obstruction to the urinary tract such as posterior urethral valves. Dilatation of the collecting system is only seen with severe VUR. The 99mTc-DMSA scan shows reduced function if unilateral or poor visualisation of the kidneys if bilateral. Frequently, there are focal defects in the kidney that can mimic the scar of UTI. Careful examination of the whole renal tract is required, as dysplasia is often seen in association with other congenital malformations of the kidney (Fig. 9).
Structural abnormalities Crossed fused ectopia, pelvic and absent kidneys may all be detected antenatally. Horseshoe kidneys are less reliably diagnosed with US as are the uncomplicated duplex kidneys.
Conclusion Prenatal US has allowed improved early management of certain conditions, particularly the obstructive uropathies. However, the majority of infants identified prenatally are
Postnatal investigation of fetal renal disease
Figure 9 Cystic dysplasia. This infant was detected antenatally with echogenic kidneys. On postnatal US, the kidneys were small and globally hyperechoeic with no corticomedullary differentiation. There were multiple small cysts seen subcortically, which are typical of those seen in cystic dysplasia.
asymptomatic. Imaging and management remains controversial with very few long-term natural history studies. Imaging principles should be the least invasive investigations using the lowest radiation burden with no unnecessary investigations.
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141 2. Borthne A, Nordshus T, Reiseter T, et al. MR urography: the future gold standard in paediatric urogenital imaging? Pediatr Radiol 1999;29:694e701. 3. Broome DR, Girguis MS, Baron PW, et al. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007;188:586e92. 4. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17:2359e62. 5. de Bruyn R, Gordon I. Diagnostic imaging of the neonatal urinary tract. In: Freeman NV, Burge DM, Griffiths DM, Malone PS, editors. Surgery of the new-born. London: Churchill Livingstone; 1994. p. 671e82. 6. Jaswon MS, Dibble L, Puri S, et al. Prospective study of outcome in antenatally diagnosed renal pelvic dilatation. Arch Dis Child Fetal Neonat Ed 1999;80:F135e8. 7. Sidhu G, Beyene J, Rosenblum ND. Outcome of isolated antenatal hydronephrosis: a systematic review and meta-analysis. Pediatr Nephrol 2006;21:218e24. 8. Lee RS, Cendron M, Kinnamon DD, et al. Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis. Pediatrics 2006;118:586e93. 9. Plant ND, Hornung RJ, Coulthard MG, et al. Does antenatal pelvic dilation predict renal scarring? Arch Dis Child Fetal Neonatal Ed 2005;90:F339e40. 10. Tibballs JM, de Bruyn R. Primary vesicoureteric refluxdhow useful is postnatal ultrasound? Arch Dis Child 1996;75:444e7. 11. Crabbe DCG, Thomas DFM, Gordon AC, et al. Use of Tc99m DMSA to show patterns of renal damage associated with prenatally detected vesicoureteral reflux. J Urol 1992;148:1239e41. 12. Elder JS. Importance of antenatal diagnosis of vesicoureteral reflux. J Urol 1992;148:1750e4. 13. Sheridan M, Jewkes F, Gough DCS. Reflux nephropathy in the first year of lifedthe role of infection. Pediatr Surg Int 1991; 6:214e7. 14. Stokland E, Hansson S, Jodal U. An alternative approach to investigation of children with urinary tract infection. Pediatr Radiol 2001;31(Suppl 1):S32. 15. Aslam M, Watson AR. Trent & Anglia MCDK Study Group. Unilateral multicystic dysplastic kidney: long term outcomes. Arch Dis Child 2006;91:820e3. 16. Slovis TL, Bernstein J, Gruskin A. Hyperechoic kidneys in the newborn and young infant. Pediatr Nephrol 1993;7:294e302. 17. de Bruyn R, Gordon I. The imaging of cystic renal disease in children. Arch Dis Child 2000;5:401e7. 18. Kaplan BS, Fay FM, Shah VM, et al. Autosomal recessive polycystic kidney disease. Pediatr Nephol 1989;3:43e9. 19. Bear JC, Parfrey PS, Morgan JM, et al. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet 1992;43:548e53. 20. Hayden CK, Swischuk LE, Davis M, Brouhard BH. Puddling: a distinguishing feature of adult polycystic kidney disease in the neonate. Am J Roentgenol 1984;142:811e2. 21. Bernstein J. Developmental abnormalities of the renal parenchyma: renal hypoplasia and dysplasia. Pathol Annu 1968;3: 213.