- Email: [email protected]
Antenatally detected urinary tract abnormalities (AUTA)
SYMPOSIUM: NEPHROLOGY
Antenatally detected urinary tract abnormalities (AUTA)
urethral valve which require early neonatal intervention. Renal abnormalities are associated with a number of different syndromes, so a careful examination of other organs must be undertaken if a renal abnormality is diagnosed antenatally. Although polycystic kidney disease and congenital nephrotic syndrome can sometimes be detected antenatally, these conditions are generally not considered within the group of abnormalities termed CAKUT. They will not be discussed in detail in this review, although they are included in tables of conditions for completeness. Abnormalities may be unilateral or bilateral. The outcomes in patients with unilateral abnormalities are very good, though investigation is required postnatally and long term follow up may be indicated. The outcome in bilateral abnormalities is also often good. Risk factors for a poor outcome include bilateral renal parenchymal abnormalities and/or oligohydramnios. Significant oligohydramnios may lead to life threatening pulmonary hypoplasia requiring intensive ventilatory support.
Corinne HF Langstaff Meeta Mallik
Abstract The kidney and urinary tract account for 30% of all antenatally detected abnormalities, with the majority involving dilatation of the urinary tracts. In nearly 40% of cases, postnatal scans are normal and no further follow up is required. Of those with a confirmed postnatal abnormality a minority will develop hypertension, renal dysfunction, or require surgery. Once an abnormality has been detected, it is important that parents are counselled promptly by those with appropriate knowledge and experience of the suspected condition. Prognosis should be guarded as postnatal scans may reveal the abnormality to be more or less severe than expected. In some cases, the condition may affect the birth plan. Some children are at increased risk of urinary tract infection, so parents should be advised of the relevant symptoms and asked to contact their primary carer promptly (with a clean catch specimen if possible) for treatment if needed. Antibiotic prophylaxis is not routinely recommended but is appropriate in selected cases. This review gives an overview of the management of conditions most likely to be encountered by general paediatricians and includes algorithms for suggested management of children with dilatation of the urinary tract and those with unilateral kidney abnormality associated with a normal contralateral kidney.
Antenatal management Suspicion of any fetal abnormality induces significant anxiety in most parents. Once an abnormality is detected, parents should receive appropriate specialist counselling. Prognosis should be guarded as postnatal scans may reveal the abnormality to be either more or less severe than expected. It is helpful to consider antenatal conditions in terms of high, moderate or low risk and management will differ accordingly (see Tables 1 and 2). Antenatally detected urinary tract abnormalities (AUTA) e moderate and mild risk features (Table 1) These are the most commonly presenting conditions and are not expected to cause significant renal dysfunction at or soon after birth e indeed in almost half of cases, postnatal scans will be normal. In most cases there is dilatation of the renal tracts which may be secondary to obstruction or vesicoureteric reflux. Measurements of dilatation should be taken across the anterioposterior (AP) plane of the renal pelvis (maximum transverse AP diameter of the renal pelvis 7 mm at 18 weeks gestation or later is considered significant). Extra-renal pelvic dilatation is of less significance, whilst dilatation of the renal calyces indicates a potentially more serious condition. A bilateral abnormality (or an abnormality in a baby with a single kidney) is of greater concern, as is a greater degree of dilatation, although the degree of antenatal dilatation does not clearly differentiate between babies who will require follow up and those who will have a normal postnatal scan. It is also not possible to predict those babies who will ultimately require surgery.
Keywords AUTA; CAKUT; ectopic kidney; multicystic dysplastic kidney; pelviureteric junction obstruction; posterior urethral valve; renal agenesis; renal dysplasia; solitary kidney; vesicoureteric junction obstruction; vesicoureteric reflux
The most common abnormalities detected by antenatal screening are those of the kidneys and urinary tract, with an incidence of 7.6/1000 live births, accounting for about 30% of all antenatally detected abnormalities. The majority involve dilatation of the renal tracts. In nearly 40% of cases, postnatal scans are normal and no further follow up is required, however, a minority of cases will have significant morbidity and it is important not to miss these. Congenital abnormalities of the renal tract (CAKUT) are the leading cause of renal failure in childhood and also result in a significant disease burden in adulthood. Of those children with abnormalities on postnatal scan, the majority will require only conservative management. There is a wide spectrum of disorders, ranging from common conditions such as vesicoureteric reflux which may be completely asymptomatic and self-resolving to rare conditions such as posterior
Antenatally detected urinary tract abnormalities (AUTA) e high risk features (Table 2) The minority of cases (approximately 3% in our series) have high risk features with bilateral renal involvement. These babies have a significant risk of severe renal dysfunction in the neonatal period and babies with bilateral renal agenesis or bilateral multicystic dysplastic kidneys do not survive. In a recent series, 50% of babies with bilateral renal disease underwent termination, and of those who were born alive, 50% died within the neonatal period. However, of the survivors, several were found to have either normal kidneys or significantly less severe conditions such as duplex kidneys, particularly if the antenatal diagnosis was of renal
Corinne H F Langstaff MB ChB MD MRCP is a Locum Consultant Paediatric Nephrologist in the Department of Paediatric Nephrology at the Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none. Meeta Mallik MB ChB BSc MRCPH is a Consultant Paediatric Nephrologist in the Department of Paediatric Nephrology at the Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 24:7
303
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Whether prophylactic antibiotics should be started Timing and nature of further investigations
AUTA moderate and mild risk features on antenatal scan (measurements of AP diameter at 18 weeks gestation or later)
Immediate postnatal management
Moderate risk features C Unilateral hydronephrosis 20 mm C Bilateral hydronephrosis 7 mm but <10 mm C Hydronephrosis 7 mm but <10 mm in a fetus with a single kidney Mild risk features C Unilateral multicystic dysplastic kidney with normal contralateral kidney C Unilateral renal dysplasia/hypoplasia C Single kidney with normal parenchyma and no dilatation C Unilateral hydronephrosis <20 mm C Non obstructing ureterocele C Other renal abnormality with normal liquor volume (eg. echogenic kidney, duplex system, horseshoe kidney)a
Following delivery, whatever the pre-natal diagnosis, the baby should be examined for: Complications resulting from oligohydramnios e.g. respiratory distress, talipes, developmental dysplasia of hips Evidence of poor urinary stream (in male infants), although a normal stream does not exclude the presence of posterior urethral valves. If posterior urethral valves are not suspected from antenatal scanning and the baby is well, observation of the urinary stream need not delay discharge. Parents should be advised to observe and report back if the stream is poor. Presence of palpable bladder or kidney (suggests significant degree of obstruction) Presence of other abnormalities that occur in association with renal abnormalities (e.g. VACTERL association) All parents should be counselled regarding symptoms of urinary tract infection (UTI) in babies. It is helpful to teach parents how to collect a clean catch urine specimen and provide them with a sterile container on discharge. They should be advised to see their GP promptly in case of: Fever (note fever may be absent in neonatal urinary tract infection) Poor feeding Vomiting and/or diarrhoea Prolonged jaundice Prophylactic antibiotics are only recommended in certain high risk cases and are no longer routinely recommended in moderate or mild risk cases.
a
These conditions should be treated according to degree of dilatation if present.
Table 1
hypoplasia or polycystic kidney disease, highlighting the fact that prognosis, even in this high risk group, should be guarded. Babies suspected of having these high risk conditions should be managed jointly by specialists in fetal and neonatal medicine, and paediatric nephrology teams. Antenatal intervention to decompress dilated systems is rarely performed nowadays as there is no clear evidence of benefit and the risks associated with intervention are significant. Sequential antenatal scans can be helpful in assessing development of pelvicalyceal dilatation and oligohydramnios which can help predict the condition of the baby at birth. An individualised management plan, made after discussion with parents and all medical teams involved, should include: Intended place of delivery (consideration should be given to delivery of the baby in a centre equipped to manage respiratory distress and renal failure in the neonatal period.) Whether or not a catheter is required (for suspected posterior urethral valves) Catheterisation can usually be delayed to allow early skin to skin contact if desired and clinically appropriate.
Imaging All babies require a postnatal ultrasound scan. Relative oliguria during the first few days of life may result in falsely reassuring ultrasound scan appearances. Therefore, the majority of babies should be discharged home at the normal time, returning for a postnatal ultrasound scan which can safely be deferred to between 4 and 6 weeks of age. In the minority of cases where a severe abnormality is suspected, an early ultrasound scan, usually within the first 48 hours of delivery may be recommended as part of the individual management plan. In our series of 350 babies referred with AUTA (Table 3), 38% had a normal postnatal ultrasound scan. The majority of abnormal postnatal scans will reveal renal tract dilatation, and subsequent imaging is required to differentiate whether this is caused by hold up or obstruction to urinary flow, or by vesicoureteric reflux. Our practice, in cases with dilated systems, is to undertake a micturating cystourethrogram (MCUG) in the first instance. An oral antibiotic should be prescribed to cover the procedure because of the risk of inducing urinary tract infection (UTI). The antibiotic used should be determined by local microbiological sensitivities. A three-day course with the MCUG taking place on the second day is recommended. If no reflux is shown, or the degree of reflux is not sufficient to account for the degree of dilatation, dynamic diuresis renography
AUTA high risk features requiring early intervention C C
C C
Bilateral hydronephrosis 10 mm Suspected bladder outlet obstruction (eg. posterior urethral valves, ureterocele) Unilateral hydronephrosis 10 mm in a fetus with a single kidney Bilateral abnormality of renal parenchyma Polycystic kidney (autosomal dominant or recessive inheritance. Check family history and consider screening parents) Congenital nephrotic syndrome (may be associated with polyhydramnios, raised AFP, large placenta, family history) Any renal abnormality associated with oligohydramnios (eg. echogenic kidneys)
Table 2
PAEDIATRICS AND CHILD HEALTH 24:7
304
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Principle diagnosis in 350 patients born with antenatally detected urinary tract abnormalities (AUTAs) Principle diagnosisa
Percentage
C Conditions presenting with dilated renal tracts Non-specific dilatation (<10 mm AP diameter of renal pelvis) Non-specific dilatation (10 mm AP diameter of renal pelvis on postnatal scan but normal MCUG and MAG3 scan) Vesicoureteric reflux (VUR) Pelviureteric junction obstruction (PUJO) Vesicoureteric junction obstruction (VUJO) Ureterocele Posterior urethral valve (PUV) C Conditions presenting with abnormality of renal parenchyma Single kidney, pelvic kidneyb and other abnormalities not listed Multicystic dysplastic kidney (MCDK) Duplex onlyb (not associated with VUR, PUJO or VUJO) Echogenic kidneys Isolated dysplasia Lost to follow up
a b
38.0 10.6 12.0 10.6 2.3 2.0 0.9 8.6 6.0 2.6 1.7 1.4 3.4
Diagnosis considered the most significant; for example, two patients categorised with PUJO also had VUR, while one patient with MCDK also had VUR. Pelvic kidney and duplex kidney with no associated abnormality are considered normal variants.
Table 3
there is no other renal abnormality (e.g. increased echogenicity). In our centre a further 10% of babies had a postnatal AP diameter greater than or equal to 10 mm but subsequent MCUG and MAG3 scans were normal. Such babies can be discharged from further follow up, but all parents should be given advice regarding symptoms of urinary tract infection and advised to have their baby seen promptly by the GP if UTI is suspected. If UTI is confirmed, referral for further investigations is warranted.
is indicated. Generally, technetium-labelled dimercaptoacetyltriglycine (MAG3) is used. This is excreted by tubular secretion with 80% being extracted at first pass, providing a high signal-tobackground ratio and hence clear images. A furosemide challenge at 15 minutes and delayed scan taken 1 hour postcontrast is helpful in differentiating between hold up (isotope clears with furosemide and on delayed images) which may resolve with time, and obstruction. Less commonly, the postnatal ultrasound scan reveals abnormal renal parenchyma. In these instances, it is important to know the percentage of function contributed by each kidney. Technetium-labelled dimercaptosuccinic acid (DMSA) scintigraphy is the investigation of choice, as DMSA is extracted, but not excreted, by functioning renal tubules. In addition to differential function, DMSA scan is helpful in documenting the presence and progression of renal scarring, and can reveal small or ectopic kidneys which may have been missed on ultrasound scan. The remainder of this article will focus on specific management of the more common congenital kidney and urinary tract abnormalities expected to survive the neonatal period (Table 3). They will be considered in two groups: renal tract dilatation and unilateral abnormalities associated with a normal contralateral kidney.
Vesicoureteric reflux This is one of the most common significant causes of antenatally detected renal tract abnormality. In our series, 12% had a final diagnosis of vesicoureteric reflux, and reflux was also present in some babies with other primary diagnoses such as multicystic dysplastic kidney (MCDK). Most commonly, mild reflux (grades 1e2) is detected, and in most centres, antibiotic prophylaxis is no longer recommended for these children, although prompt treatment of any urinary tract infection is important and recurrent UTI might prompt a trial of prophylaxis in individual cases. Antibiotic prophylaxis has generally been prescribed for high grade reflux (grades IIIeV), but there is an increasing body of data suggesting this treatment does not in fact protect against pyelonephritis or renal scarring. A DMSA should be considered to look for reflux associated dysplasia and differential function. Serum creatinine at the time of scan will establish overall renal function. Ongoing follow up is indicated for these children with vigilance for urine infection, whether or not prophylactic antibiotics are prescribed. If recurrent urinary tract infections (especially upper tract symptoms) develop despite antibiotic prophylaxis, it is
Renal tract dilatation (Figure 1) Non-specific mild dilatation It is important to recognise that the most common cause of antenatally detected hydronephrosis is non-specific mild dilatation, found in 38% of cases in our series. It is generally accepted that postnatal AP pelvic diameter less than 10 mm is within normal limits, providing: there is no calyceal or ureteric dilatation renal size is normal
PAEDIATRICS AND CHILD HEALTH 24:7
305
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Postnatal scan AP pelvic diameter >20mm Or AP diameter >10mm and clinical history of: • oligohydramnios • palpable kidney or bladder • or poor urinary stream • or solitary kidney •
Discuss with consultant experienced in management of severe renal abnormality Refer to individual management plan
•
Postnatal scan AP pelvic diameter >10mm and <20mm and no clinical history of: • oligohydramnios • palpable kidney or bladder • or poor urinary stream Routine MCUG with antibiotic cover for 3 days starting the day before the MCUG
Postnatal scan AP pelvic diameter <10mm and • no calyceal or ureteric dilatation • normal renal size • no other renal abnormality
Non specific mild dilatation No antibiotic prophylaxis No routine follow up Review if UTI diagnosed
• • •
• • Severe reflux ( ≥ grade 3)
Consider antibiotic prophylaxis
• •
• •
Mild reflux(≤ grade 2)
• • •
No antibiotic prophylaxis Regular follow up with vigilance for UTI Consider prophylaxis if UTI diagnosed
No reflux or Degree of reflux not sufficient to account for degree of dilatation
MAG 3 with furosemide and delayed image
Abnormal
Normal
DMSA Continue follow up with vigilance for UTI
•
Repeat USS 2 years age Consider stopping antibiotics if normal and no UTIs for previous year (alternatively continue prophylaxis until out of nappies – discuss preference of parents) Consider DMSA
•
Repeat USS 5 years age
Discharge if: • No scarring • Normal renal size • No dilatation • No UTI off prophylaxis for at least one year
• •
Repeat USS 2 years age Consider DMSA
Repeat USS at 1 yr
Discharge if normal Assess: • Scarring • Renal size • Ongoing UTIs
Unilateral scarring and/or ongoing UTIs - refer to paediatrician with appropriate expertise to monitor for and manage hypertension / UTIs
Discuss with relevant paediatric urology team
Bilateral scarring and/or bilateral small kidneys – refer to paediatrician with appropriate expertise to monitor renal function and manage early CKD
Figure 1 Algorithm for management of urinary tract dilatation on postnatal ultrasound.
reasonable to undertake a DMSA scan to look for new scarring, but ideally this should be delayed until 4e6 months following the acute infection. If new scarring is detected, or there is ongoing morbidity, an anti-reflux procedure should be considered. Our practice is to repeat an ultrasound at 2 years of age in all cases of reflux. A DMSA may also be considered at this time, especially if there have been confirmed UTIs. This can inform the decision as to whether or not to discontinue prophylactic antibiotics if they have been commenced. Some practitioners delay stopping prophylaxis until the child is out of nappies, the
PAEDIATRICS AND CHILD HEALTH 24:7
philosophy being that urine infections are easier to diagnose once a child is potty trained. We undertake a further ultrasound scan at 5 years of age in children with a high grade reflux. Again, a DMSA scan can be informative if there have been ongoing upper tract UTIs. The pathway for further follow up depends on the result of these scans and whether or not there are ongoing urinary tract infections. If there is: normal renal function no scarring 306
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
narrowing in the posterior urethra, and will also determine whether there is vesicoureteric reflux. Once bladder drainage is ensured with a catheter, endoscopic ablation of the valve can be delayed until the child is stable. Bladder abnormalities range from large low pressure to small high pressure systems. The latter are a concern as they may induce more rapid decline of renal function, both of native kidneys and any future transplant. Many boys need to undertake clean intermittent self catheterisation to remain dry and infection free. Some cases of PUV are not diagnosed antenatally, so any baby boy with a poor urinary stream should be investigated, initially with an ultrasound scan. Some mild cases present later in life, with wetting or recurrent urine infection, or with a history of straining or sitting to urinate. In older children catheterisation for MCUG can be physically and psychologically traumatic and this trauma can be significantly reduced by the use of Entonox.
normal renal size no dilatation of renal tract no UTI off prophylaxis for at least one year patients can be discharged to primary care with the option of re-referral if recurrent urine infections develop. If unilateral renal scarring is identified, there is a small (11% in one study) long term risk of hypertension and lifelong follow up is recommended. Initially we recommend management by a paediatrician with appropriate expertise to monitor for and manage hypertension. Once the blood pressure can be measured using an adult cuff, an annual review, consisting of measurement of blood pressure and urinalysis looking for proteinuria, can be undertaken by the general practitioner. In the case of bilateral renal scarring, there is a risk of long term deterioration of renal function as well as hypertension. These children should be managed by paediatricians experienced in the treatment of chronic kidney disease in childhood.
Unilateral parenchymal abnormalities with normal contralateral kidney (Figure 4)
Pelviureteric or vesicoureteric junction obstruction If there is no reflux on MCUG, or the degree of reflux is insufficient to account for the degree of dilatation, hold up or obstruction to the outflow of urine from the kidney is likely. In our series, 10.6% of the 350 cases of antenatally detected urinary tract abnormality had pelviureteric junction obstruction (PUJO) and 2.3% had vesicoureteric junction obstruction (VUJO) (Figure 2). Investigation is aimed at assessing the site and degree of restriction to urinary flow, and the differential renal function. Patients require careful monitoring with regular ultrasound scans and sequential MAG 3 scans and should be managed by, or in close consultation with, a paediatric urologist. Indications for surgery include: Obstructed curve on MAG 3 scan with no response to furosemide and persistence of isotope in delayed images, especially in the presence of differential renal function less than 40% increasing dilatation on sequential ultrasound scans Pain Pyelonephritis
Providing there is one normally functioning kidney, prognosis for renal function is extremely good, especially in the short to medium term. However, there are reports demonstrating increased incidence of proteinuria, hypertension and reduced glomerular filtration rate (GFR) in adolescence, suggesting a risk of hyperfiltration injury. One cohort study of adults with congenital single kidney found the prevalence of proteinuria, hypertension and reduced GFR to be over 30%, with kidney length under 120 mm and presence of proteinuria associated with a higher risk of renal insufficiency. In view of this, lifelong follow up of patients is recommended, with at least annual review of blood pressure and urinalysis, and intermittent (we would suggest every 5 years), serum creatinine to measure renal function. In childhood, sequential ultrasounds at 2, 5 and 10 years are helpful in determining whether or not there is satisfactory contralateral compensatory hypertrophy. Paediatric growth charts for single kidneys are available. Children with any of the following features should be referred for follow up by a paediatric nephrologist. hypertension proteinuria greater than 20 mg/mmol creatinine on an early morning specimen lack of compensatory hypertrophy on sequential ultrasound scan reduced GFR
Posterior urethral valve This condition affects only boys and is rare, accounting for only 0.9% of cases in our series. The valve, present from about 7 week’s gestation, is an oblique membrane with a small aperture which obstructs the urinary flow. It occurs in the posterior urethra and is thought to be a remnant of the mullerian duct or cloacal membrane. More than 80% of cases are picked up antenatally. The severity of symptoms varies from case to case, with both renal dysfunction and bladder symptoms being common: (Figure 3) 20% develop established renal failure in childhood 40% have chronic kidney disease 40e60% have vesicoureteric reflux 75% have voiding problems The baby should be catheterised at birth, and a significant post-obstructive diuresis with electrolyte imbalance (hyponatremia, hyperkalaemia, acidosis) should be anticipated and carefully managed. Prophylactic antibiotics are recommended and any urine infection should be treated promptly. The diagnosis should be confirmed on MCUG which will show a
PAEDIATRICS AND CHILD HEALTH 24:7
Multicystic dysplastic kidney A multicystic dysplastic kidney (MCDK) occurs when the ureteric bud fails to join with the developing renal tissue during embryogenesis. The resulting kidney is non-functioning and consists of multiple tense non-communicating cysts with no discernible renal cortex. The ultrasound appearances can be diagnostic, but a postnatal DMSA scan is recommended in most centres to confirm lack of function and presence of a normal contralateral kidney. This should not be undertaken prior to 1 month of age, as renal function is inadequate to produce satisfactory images. Over time, many MCDK involute and there is no longer thought to be an increased risk of malignancy or hypertension when compared with the general population.
307
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Delayed excretion of isotope by enlarged left kidney
Rapid uptake and excretion of isotope by right kidney
Bladder filling
Left kidney – continuing accumulation of isotope even after injection of furosemide
Isotope persists in left kidney on delyed image (60 min post injection)
Normal right kidney rapid excretion of isotope
Figure 2 MAG 3 scan in patient with left sided PUJ obstruction.
There is, however, an increased incidence of abnormality of the contralateral kidney, with studies showing vesicoureteric reflux in 5e28% of cases. There is debate as to whether all children with MCDK should have a micturating cystourethrogram (MCUG). This is an invasive and traumatic test, and with current practice being to restrict antibiotic prophylaxis to more severe cases of reflux, it should only be undertaken if the result
will alter management. Our practice is to undertake MCUG only when ultrasound suggests the possibility of reflux, or where there is a history of a febrile urinary tract infection. Unilateral renal dysplasia/hypoplasia In these conditions, measurement of the serum creatinine in combination with a DMSA scan taken at about 3 months is
Bilateral dilated tortonous ureters with grade 5 vesico-ureteric reflux
Thick-walled trabeculated bladder Dilated posterior urethra Site of posterior urethral valve Figure 3 MCUG in patient with posterior urethral valve associated with bilateral grade 5 vesicoureteric reflux.
PAEDIATRICS AND CHILD HEALTH 24:7
308
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
USS at 4 – 6 weeks post delivery
Ectopic kidney identified
no • • •
If otherwise normal, no need for further follow up
yes
Febrile UTI Contralateral pelvic AP diameter ≥10 mm Ureteric dilatation
no
yes
•
3 months age: • DMSA • Creatinine (abnormal if above 35 µmol/l) • blood pressure • urinalysis
•
Consider MCUG(with antibiotic cover) and/or MAG3 scan Consider prophylaxis
Indications for referral to Paediatric Nephrologist at any stage:
Annual follow up: • Blood pressure • urinalysis
Additionally at 2, 5 and 10 yr follow up: • USS • Creatinine (calculate eGFRΔ)
•
Hypertension
•
Proteinuria >20 mg/mmol creatinine on early morning specimen
•
Lack of compensatory hypertrophy on USS
•
eGFR < 90 ml/min/1.73m2
After 10 years, discharge to GP for lifelong annual: • Blood pressure • Urinalysis Δ From the age of 2, estimated GFR should always be calculated from serum creatinine. The formula is: eGFR = (K x ht (cm))/ creatinine (mmol). K is traditionally 40, but will differ according to method of measurement and should be discussed locally.
Figure 4 Algorithm for management of unilateral MCDK, renal dysplasia, hypoplasia or agenesis with normal contralateral kidney.
helpful to estimate the total renal function and the percentage of function contributed by the dysplastic or hypoplastic kidney. There is an association with vesicoureteric reflux, so there should be a low threshold for undertaking a MCUG. If there are recurrent UTI despite antibiotic prophylaxis, whether to undertake an anti-reflux procedure or simply remove the abnormal kidney and ureter will be a decision informed by the relative function of the affected side. Many urologists consider the benefits of removing a kidney that is contributing less than 10% of total renal function outweigh the risks.
PAEDIATRICS AND CHILD HEALTH 24:7
Hypertension is associated with renal dysplasia, and regular blood pressure measurements are indicated. If there is significantly reduced function (less than 10%) in association with hypertension, removal of the abnormal kidney may be considered and may be curative. Ectopic kidney When there is apparent unilateral renal agenesis, a DMSA may be helpful, as occasionally an ectopic (usually pelvic) kidney is discovered. This provides reassurance in terms of increased
309
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
and renal scars? A randomized controlled trial. Pediatrics 2008; 121: e1489e94. Phillips D, Watson AR, Collier J. Distress and radiological investigations of the urinary tract in children. Eur J Pediatr 1996; 155: 684e7. Thomas DFM, Rickwood AMK, Duffy PG. Essentials of paediatric urology. 1st Edn. London: Martin Dunitz, 2002. For a general review of congenital nephrotic syndrome: Jalanko H. Congenital nephrotic syndrome. Pediatr Nephrol 2009; 24: 2121e8. For a general review of autosomal recessive polycystic kidney disease: €scher R, Bu €scher AK, Weber S, Hegen B, Vester U, Hoyer PF. Clinical Bu manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes. Pediatr Nephrol Oct 2013; http://dx.doi.org/10.1007/s00467-013-2634-1. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics 2003; 111: 1072e80.
volume of functioning renal tissue, and though ectopic kidneys may be at a slightly greater risk of traumatic damage, they are usually otherwise asymptomatic. Patients with a normal sized ectopic kidney of otherwise normal appearance do not require any specialised follow up.
Summary Improved antenatal screening has increased the numbers of renal abnormalities detected before birth. This can induce considerable anxiety in parents, and expert counselling is required soon after the diagnosis has been made, both in mild and severe cases. All patients require a postnatal ultrasound, and in about 40% of cases this will be normal and the baby can be discharged from follow up. Approximately 35% of babies will have a significant degree of renal tract dilatation. About a third of these have normal follow up investigations, one third have vesicoureteric reflux and one third hold up or obstruction to urinary flow. For cases of vesicoureteric reflux, management centres on prompt diagnosis and treatment of UTI. In mild reflux, antibiotic prophylaxis is not generally recommended but can be considered in individual cases experiencing recurrent infections. There is contention as to whether prophylaxis should be routinely used in higher grades of reflux. Babies with hold up or obstruction to urinary flow (PUJO or VUJO) need close follow up. Management if directed towards detecting whether obstruction is threatening renal health. Most cases can be treated conservatively, with surgery being reserved for the minority of cases developing increasing dilatation, reduction in differential function or symptoms of pain or pyelonephritis. Unilateral abnormalities of renal parenchyma, such as MCDK, dysplasia, hypoplasia or aplasia are present in about 20% of babies with AUTA. The prognosis is generally good, providing the contralateral kidney is normal and undergoes compensatory hypertrophy. Nevertheless, lifelong annual assessments of renal function and urinalysis are recommended because of the small risk of hyperfiltration injury to the ‘normal’ kidney. Serious abnormalities which affect both kidneys, such as posterior urethral valve or bilateral parenchymal abnormality such as bilateral dysplasia are rare but commonly result in renal dysfunction in childhood and require specialist management. A
Practice points C
C
C
C
C
C
C
FURTHER READING Dudley JA, Haworth JM, McGraw ME, Frank JD, Tizard EJ. Clinical relevance and implications of antenatal hydronephrosis. Arch Dis Child Fetal Neonatal Ed 1997; 76: F31e4. Mallik M, Watson AR. Antenatally detected urinary tract abnormalities: more detection but less action. Pediatr Nephrol 2008; 23: 897e904. Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis
PAEDIATRICS AND CHILD HEALTH 24:7
Congenital abnormalities of the kidney and urinary tract are the commonest abnormalities detected by antenatal screening Prognosis should be guarded during antenatal counselling as the outcome may be better or worse than expected. 30% of babies will have normal postnatal scans and the majority of the remainder can be treated conservatively and will have a good prognosis. Many cases of renal tract dilatation can be managed conservatively, but close monitoring of renal health is needed. Prophylactic antibiotics are no longer recommended for mild grades of reflux, and their use in high grade reflux is contentious. Unilateral abnormalities with normal contralateral kidney have an excellent prognosis, but lifelong annual review of blood pressure and urinalysis is recommended because of the long term risk of hyperfiltration injury Babies with high risk features should be jointly managed from the antenatal stage by fetal, neonatal and paediatric nephrology teams.
Acknowledgements The authors would like to thank Dr Andrew Lunn for his helpful comments on this manuscript.
310
Ó 2014 Elsevier Ltd. All rights reserved.
Antenatally detected urinary tract abnormalities (AUTA)
urethral valve which require early neonatal intervention. Renal abnormalities are associated with a number of different syndromes, so a careful examination of other organs must be undertaken if a renal abnormality is diagnosed antenatally. Although polycystic kidney disease and congenital nephrotic syndrome can sometimes be detected antenatally, these conditions are generally not considered within the group of abnormalities termed CAKUT. They will not be discussed in detail in this review, although they are included in tables of conditions for completeness. Abnormalities may be unilateral or bilateral. The outcomes in patients with unilateral abnormalities are very good, though investigation is required postnatally and long term follow up may be indicated. The outcome in bilateral abnormalities is also often good. Risk factors for a poor outcome include bilateral renal parenchymal abnormalities and/or oligohydramnios. Significant oligohydramnios may lead to life threatening pulmonary hypoplasia requiring intensive ventilatory support.
Corinne HF Langstaff Meeta Mallik
Abstract The kidney and urinary tract account for 30% of all antenatally detected abnormalities, with the majority involving dilatation of the urinary tracts. In nearly 40% of cases, postnatal scans are normal and no further follow up is required. Of those with a confirmed postnatal abnormality a minority will develop hypertension, renal dysfunction, or require surgery. Once an abnormality has been detected, it is important that parents are counselled promptly by those with appropriate knowledge and experience of the suspected condition. Prognosis should be guarded as postnatal scans may reveal the abnormality to be more or less severe than expected. In some cases, the condition may affect the birth plan. Some children are at increased risk of urinary tract infection, so parents should be advised of the relevant symptoms and asked to contact their primary carer promptly (with a clean catch specimen if possible) for treatment if needed. Antibiotic prophylaxis is not routinely recommended but is appropriate in selected cases. This review gives an overview of the management of conditions most likely to be encountered by general paediatricians and includes algorithms for suggested management of children with dilatation of the urinary tract and those with unilateral kidney abnormality associated with a normal contralateral kidney.
Antenatal management Suspicion of any fetal abnormality induces significant anxiety in most parents. Once an abnormality is detected, parents should receive appropriate specialist counselling. Prognosis should be guarded as postnatal scans may reveal the abnormality to be either more or less severe than expected. It is helpful to consider antenatal conditions in terms of high, moderate or low risk and management will differ accordingly (see Tables 1 and 2). Antenatally detected urinary tract abnormalities (AUTA) e moderate and mild risk features (Table 1) These are the most commonly presenting conditions and are not expected to cause significant renal dysfunction at or soon after birth e indeed in almost half of cases, postnatal scans will be normal. In most cases there is dilatation of the renal tracts which may be secondary to obstruction or vesicoureteric reflux. Measurements of dilatation should be taken across the anterioposterior (AP) plane of the renal pelvis (maximum transverse AP diameter of the renal pelvis 7 mm at 18 weeks gestation or later is considered significant). Extra-renal pelvic dilatation is of less significance, whilst dilatation of the renal calyces indicates a potentially more serious condition. A bilateral abnormality (or an abnormality in a baby with a single kidney) is of greater concern, as is a greater degree of dilatation, although the degree of antenatal dilatation does not clearly differentiate between babies who will require follow up and those who will have a normal postnatal scan. It is also not possible to predict those babies who will ultimately require surgery.
Keywords AUTA; CAKUT; ectopic kidney; multicystic dysplastic kidney; pelviureteric junction obstruction; posterior urethral valve; renal agenesis; renal dysplasia; solitary kidney; vesicoureteric junction obstruction; vesicoureteric reflux
The most common abnormalities detected by antenatal screening are those of the kidneys and urinary tract, with an incidence of 7.6/1000 live births, accounting for about 30% of all antenatally detected abnormalities. The majority involve dilatation of the renal tracts. In nearly 40% of cases, postnatal scans are normal and no further follow up is required, however, a minority of cases will have significant morbidity and it is important not to miss these. Congenital abnormalities of the renal tract (CAKUT) are the leading cause of renal failure in childhood and also result in a significant disease burden in adulthood. Of those children with abnormalities on postnatal scan, the majority will require only conservative management. There is a wide spectrum of disorders, ranging from common conditions such as vesicoureteric reflux which may be completely asymptomatic and self-resolving to rare conditions such as posterior
Antenatally detected urinary tract abnormalities (AUTA) e high risk features (Table 2) The minority of cases (approximately 3% in our series) have high risk features with bilateral renal involvement. These babies have a significant risk of severe renal dysfunction in the neonatal period and babies with bilateral renal agenesis or bilateral multicystic dysplastic kidneys do not survive. In a recent series, 50% of babies with bilateral renal disease underwent termination, and of those who were born alive, 50% died within the neonatal period. However, of the survivors, several were found to have either normal kidneys or significantly less severe conditions such as duplex kidneys, particularly if the antenatal diagnosis was of renal
Corinne H F Langstaff MB ChB MD MRCP is a Locum Consultant Paediatric Nephrologist in the Department of Paediatric Nephrology at the Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none. Meeta Mallik MB ChB BSc MRCPH is a Consultant Paediatric Nephrologist in the Department of Paediatric Nephrology at the Queen’s Medical Centre, Nottingham, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 24:7
303
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Whether prophylactic antibiotics should be started Timing and nature of further investigations
AUTA moderate and mild risk features on antenatal scan (measurements of AP diameter at 18 weeks gestation or later)
Immediate postnatal management
Moderate risk features C Unilateral hydronephrosis 20 mm C Bilateral hydronephrosis 7 mm but <10 mm C Hydronephrosis 7 mm but <10 mm in a fetus with a single kidney Mild risk features C Unilateral multicystic dysplastic kidney with normal contralateral kidney C Unilateral renal dysplasia/hypoplasia C Single kidney with normal parenchyma and no dilatation C Unilateral hydronephrosis <20 mm C Non obstructing ureterocele C Other renal abnormality with normal liquor volume (eg. echogenic kidney, duplex system, horseshoe kidney)a
Following delivery, whatever the pre-natal diagnosis, the baby should be examined for: Complications resulting from oligohydramnios e.g. respiratory distress, talipes, developmental dysplasia of hips Evidence of poor urinary stream (in male infants), although a normal stream does not exclude the presence of posterior urethral valves. If posterior urethral valves are not suspected from antenatal scanning and the baby is well, observation of the urinary stream need not delay discharge. Parents should be advised to observe and report back if the stream is poor. Presence of palpable bladder or kidney (suggests significant degree of obstruction) Presence of other abnormalities that occur in association with renal abnormalities (e.g. VACTERL association) All parents should be counselled regarding symptoms of urinary tract infection (UTI) in babies. It is helpful to teach parents how to collect a clean catch urine specimen and provide them with a sterile container on discharge. They should be advised to see their GP promptly in case of: Fever (note fever may be absent in neonatal urinary tract infection) Poor feeding Vomiting and/or diarrhoea Prolonged jaundice Prophylactic antibiotics are only recommended in certain high risk cases and are no longer routinely recommended in moderate or mild risk cases.
a
These conditions should be treated according to degree of dilatation if present.
Table 1
hypoplasia or polycystic kidney disease, highlighting the fact that prognosis, even in this high risk group, should be guarded. Babies suspected of having these high risk conditions should be managed jointly by specialists in fetal and neonatal medicine, and paediatric nephrology teams. Antenatal intervention to decompress dilated systems is rarely performed nowadays as there is no clear evidence of benefit and the risks associated with intervention are significant. Sequential antenatal scans can be helpful in assessing development of pelvicalyceal dilatation and oligohydramnios which can help predict the condition of the baby at birth. An individualised management plan, made after discussion with parents and all medical teams involved, should include: Intended place of delivery (consideration should be given to delivery of the baby in a centre equipped to manage respiratory distress and renal failure in the neonatal period.) Whether or not a catheter is required (for suspected posterior urethral valves) Catheterisation can usually be delayed to allow early skin to skin contact if desired and clinically appropriate.
Imaging All babies require a postnatal ultrasound scan. Relative oliguria during the first few days of life may result in falsely reassuring ultrasound scan appearances. Therefore, the majority of babies should be discharged home at the normal time, returning for a postnatal ultrasound scan which can safely be deferred to between 4 and 6 weeks of age. In the minority of cases where a severe abnormality is suspected, an early ultrasound scan, usually within the first 48 hours of delivery may be recommended as part of the individual management plan. In our series of 350 babies referred with AUTA (Table 3), 38% had a normal postnatal ultrasound scan. The majority of abnormal postnatal scans will reveal renal tract dilatation, and subsequent imaging is required to differentiate whether this is caused by hold up or obstruction to urinary flow, or by vesicoureteric reflux. Our practice, in cases with dilated systems, is to undertake a micturating cystourethrogram (MCUG) in the first instance. An oral antibiotic should be prescribed to cover the procedure because of the risk of inducing urinary tract infection (UTI). The antibiotic used should be determined by local microbiological sensitivities. A three-day course with the MCUG taking place on the second day is recommended. If no reflux is shown, or the degree of reflux is not sufficient to account for the degree of dilatation, dynamic diuresis renography
AUTA high risk features requiring early intervention C C
C C
Bilateral hydronephrosis 10 mm Suspected bladder outlet obstruction (eg. posterior urethral valves, ureterocele) Unilateral hydronephrosis 10 mm in a fetus with a single kidney Bilateral abnormality of renal parenchyma Polycystic kidney (autosomal dominant or recessive inheritance. Check family history and consider screening parents) Congenital nephrotic syndrome (may be associated with polyhydramnios, raised AFP, large placenta, family history) Any renal abnormality associated with oligohydramnios (eg. echogenic kidneys)
Table 2
PAEDIATRICS AND CHILD HEALTH 24:7
304
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Principle diagnosis in 350 patients born with antenatally detected urinary tract abnormalities (AUTAs) Principle diagnosisa
Percentage
C Conditions presenting with dilated renal tracts Non-specific dilatation (<10 mm AP diameter of renal pelvis) Non-specific dilatation (10 mm AP diameter of renal pelvis on postnatal scan but normal MCUG and MAG3 scan) Vesicoureteric reflux (VUR) Pelviureteric junction obstruction (PUJO) Vesicoureteric junction obstruction (VUJO) Ureterocele Posterior urethral valve (PUV) C Conditions presenting with abnormality of renal parenchyma Single kidney, pelvic kidneyb and other abnormalities not listed Multicystic dysplastic kidney (MCDK) Duplex onlyb (not associated with VUR, PUJO or VUJO) Echogenic kidneys Isolated dysplasia Lost to follow up
a b
38.0 10.6 12.0 10.6 2.3 2.0 0.9 8.6 6.0 2.6 1.7 1.4 3.4
Diagnosis considered the most significant; for example, two patients categorised with PUJO also had VUR, while one patient with MCDK also had VUR. Pelvic kidney and duplex kidney with no associated abnormality are considered normal variants.
Table 3
there is no other renal abnormality (e.g. increased echogenicity). In our centre a further 10% of babies had a postnatal AP diameter greater than or equal to 10 mm but subsequent MCUG and MAG3 scans were normal. Such babies can be discharged from further follow up, but all parents should be given advice regarding symptoms of urinary tract infection and advised to have their baby seen promptly by the GP if UTI is suspected. If UTI is confirmed, referral for further investigations is warranted.
is indicated. Generally, technetium-labelled dimercaptoacetyltriglycine (MAG3) is used. This is excreted by tubular secretion with 80% being extracted at first pass, providing a high signal-tobackground ratio and hence clear images. A furosemide challenge at 15 minutes and delayed scan taken 1 hour postcontrast is helpful in differentiating between hold up (isotope clears with furosemide and on delayed images) which may resolve with time, and obstruction. Less commonly, the postnatal ultrasound scan reveals abnormal renal parenchyma. In these instances, it is important to know the percentage of function contributed by each kidney. Technetium-labelled dimercaptosuccinic acid (DMSA) scintigraphy is the investigation of choice, as DMSA is extracted, but not excreted, by functioning renal tubules. In addition to differential function, DMSA scan is helpful in documenting the presence and progression of renal scarring, and can reveal small or ectopic kidneys which may have been missed on ultrasound scan. The remainder of this article will focus on specific management of the more common congenital kidney and urinary tract abnormalities expected to survive the neonatal period (Table 3). They will be considered in two groups: renal tract dilatation and unilateral abnormalities associated with a normal contralateral kidney.
Vesicoureteric reflux This is one of the most common significant causes of antenatally detected renal tract abnormality. In our series, 12% had a final diagnosis of vesicoureteric reflux, and reflux was also present in some babies with other primary diagnoses such as multicystic dysplastic kidney (MCDK). Most commonly, mild reflux (grades 1e2) is detected, and in most centres, antibiotic prophylaxis is no longer recommended for these children, although prompt treatment of any urinary tract infection is important and recurrent UTI might prompt a trial of prophylaxis in individual cases. Antibiotic prophylaxis has generally been prescribed for high grade reflux (grades IIIeV), but there is an increasing body of data suggesting this treatment does not in fact protect against pyelonephritis or renal scarring. A DMSA should be considered to look for reflux associated dysplasia and differential function. Serum creatinine at the time of scan will establish overall renal function. Ongoing follow up is indicated for these children with vigilance for urine infection, whether or not prophylactic antibiotics are prescribed. If recurrent urinary tract infections (especially upper tract symptoms) develop despite antibiotic prophylaxis, it is
Renal tract dilatation (Figure 1) Non-specific mild dilatation It is important to recognise that the most common cause of antenatally detected hydronephrosis is non-specific mild dilatation, found in 38% of cases in our series. It is generally accepted that postnatal AP pelvic diameter less than 10 mm is within normal limits, providing: there is no calyceal or ureteric dilatation renal size is normal
PAEDIATRICS AND CHILD HEALTH 24:7
305
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Postnatal scan AP pelvic diameter >20mm Or AP diameter >10mm and clinical history of: • oligohydramnios • palpable kidney or bladder • or poor urinary stream • or solitary kidney •
Discuss with consultant experienced in management of severe renal abnormality Refer to individual management plan
•
Postnatal scan AP pelvic diameter >10mm and <20mm and no clinical history of: • oligohydramnios • palpable kidney or bladder • or poor urinary stream Routine MCUG with antibiotic cover for 3 days starting the day before the MCUG
Postnatal scan AP pelvic diameter <10mm and • no calyceal or ureteric dilatation • normal renal size • no other renal abnormality
Non specific mild dilatation No antibiotic prophylaxis No routine follow up Review if UTI diagnosed
• • •
• • Severe reflux ( ≥ grade 3)
Consider antibiotic prophylaxis
• •
• •
Mild reflux(≤ grade 2)
• • •
No antibiotic prophylaxis Regular follow up with vigilance for UTI Consider prophylaxis if UTI diagnosed
No reflux or Degree of reflux not sufficient to account for degree of dilatation
MAG 3 with furosemide and delayed image
Abnormal
Normal
DMSA Continue follow up with vigilance for UTI
•
Repeat USS 2 years age Consider stopping antibiotics if normal and no UTIs for previous year (alternatively continue prophylaxis until out of nappies – discuss preference of parents) Consider DMSA
•
Repeat USS 5 years age
Discharge if: • No scarring • Normal renal size • No dilatation • No UTI off prophylaxis for at least one year
• •
Repeat USS 2 years age Consider DMSA
Repeat USS at 1 yr
Discharge if normal Assess: • Scarring • Renal size • Ongoing UTIs
Unilateral scarring and/or ongoing UTIs - refer to paediatrician with appropriate expertise to monitor for and manage hypertension / UTIs
Discuss with relevant paediatric urology team
Bilateral scarring and/or bilateral small kidneys – refer to paediatrician with appropriate expertise to monitor renal function and manage early CKD
Figure 1 Algorithm for management of urinary tract dilatation on postnatal ultrasound.
reasonable to undertake a DMSA scan to look for new scarring, but ideally this should be delayed until 4e6 months following the acute infection. If new scarring is detected, or there is ongoing morbidity, an anti-reflux procedure should be considered. Our practice is to repeat an ultrasound at 2 years of age in all cases of reflux. A DMSA may also be considered at this time, especially if there have been confirmed UTIs. This can inform the decision as to whether or not to discontinue prophylactic antibiotics if they have been commenced. Some practitioners delay stopping prophylaxis until the child is out of nappies, the
PAEDIATRICS AND CHILD HEALTH 24:7
philosophy being that urine infections are easier to diagnose once a child is potty trained. We undertake a further ultrasound scan at 5 years of age in children with a high grade reflux. Again, a DMSA scan can be informative if there have been ongoing upper tract UTIs. The pathway for further follow up depends on the result of these scans and whether or not there are ongoing urinary tract infections. If there is: normal renal function no scarring 306
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
narrowing in the posterior urethra, and will also determine whether there is vesicoureteric reflux. Once bladder drainage is ensured with a catheter, endoscopic ablation of the valve can be delayed until the child is stable. Bladder abnormalities range from large low pressure to small high pressure systems. The latter are a concern as they may induce more rapid decline of renal function, both of native kidneys and any future transplant. Many boys need to undertake clean intermittent self catheterisation to remain dry and infection free. Some cases of PUV are not diagnosed antenatally, so any baby boy with a poor urinary stream should be investigated, initially with an ultrasound scan. Some mild cases present later in life, with wetting or recurrent urine infection, or with a history of straining or sitting to urinate. In older children catheterisation for MCUG can be physically and psychologically traumatic and this trauma can be significantly reduced by the use of Entonox.
normal renal size no dilatation of renal tract no UTI off prophylaxis for at least one year patients can be discharged to primary care with the option of re-referral if recurrent urine infections develop. If unilateral renal scarring is identified, there is a small (11% in one study) long term risk of hypertension and lifelong follow up is recommended. Initially we recommend management by a paediatrician with appropriate expertise to monitor for and manage hypertension. Once the blood pressure can be measured using an adult cuff, an annual review, consisting of measurement of blood pressure and urinalysis looking for proteinuria, can be undertaken by the general practitioner. In the case of bilateral renal scarring, there is a risk of long term deterioration of renal function as well as hypertension. These children should be managed by paediatricians experienced in the treatment of chronic kidney disease in childhood.
Unilateral parenchymal abnormalities with normal contralateral kidney (Figure 4)
Pelviureteric or vesicoureteric junction obstruction If there is no reflux on MCUG, or the degree of reflux is insufficient to account for the degree of dilatation, hold up or obstruction to the outflow of urine from the kidney is likely. In our series, 10.6% of the 350 cases of antenatally detected urinary tract abnormality had pelviureteric junction obstruction (PUJO) and 2.3% had vesicoureteric junction obstruction (VUJO) (Figure 2). Investigation is aimed at assessing the site and degree of restriction to urinary flow, and the differential renal function. Patients require careful monitoring with regular ultrasound scans and sequential MAG 3 scans and should be managed by, or in close consultation with, a paediatric urologist. Indications for surgery include: Obstructed curve on MAG 3 scan with no response to furosemide and persistence of isotope in delayed images, especially in the presence of differential renal function less than 40% increasing dilatation on sequential ultrasound scans Pain Pyelonephritis
Providing there is one normally functioning kidney, prognosis for renal function is extremely good, especially in the short to medium term. However, there are reports demonstrating increased incidence of proteinuria, hypertension and reduced glomerular filtration rate (GFR) in adolescence, suggesting a risk of hyperfiltration injury. One cohort study of adults with congenital single kidney found the prevalence of proteinuria, hypertension and reduced GFR to be over 30%, with kidney length under 120 mm and presence of proteinuria associated with a higher risk of renal insufficiency. In view of this, lifelong follow up of patients is recommended, with at least annual review of blood pressure and urinalysis, and intermittent (we would suggest every 5 years), serum creatinine to measure renal function. In childhood, sequential ultrasounds at 2, 5 and 10 years are helpful in determining whether or not there is satisfactory contralateral compensatory hypertrophy. Paediatric growth charts for single kidneys are available. Children with any of the following features should be referred for follow up by a paediatric nephrologist. hypertension proteinuria greater than 20 mg/mmol creatinine on an early morning specimen lack of compensatory hypertrophy on sequential ultrasound scan reduced GFR
Posterior urethral valve This condition affects only boys and is rare, accounting for only 0.9% of cases in our series. The valve, present from about 7 week’s gestation, is an oblique membrane with a small aperture which obstructs the urinary flow. It occurs in the posterior urethra and is thought to be a remnant of the mullerian duct or cloacal membrane. More than 80% of cases are picked up antenatally. The severity of symptoms varies from case to case, with both renal dysfunction and bladder symptoms being common: (Figure 3) 20% develop established renal failure in childhood 40% have chronic kidney disease 40e60% have vesicoureteric reflux 75% have voiding problems The baby should be catheterised at birth, and a significant post-obstructive diuresis with electrolyte imbalance (hyponatremia, hyperkalaemia, acidosis) should be anticipated and carefully managed. Prophylactic antibiotics are recommended and any urine infection should be treated promptly. The diagnosis should be confirmed on MCUG which will show a
PAEDIATRICS AND CHILD HEALTH 24:7
Multicystic dysplastic kidney A multicystic dysplastic kidney (MCDK) occurs when the ureteric bud fails to join with the developing renal tissue during embryogenesis. The resulting kidney is non-functioning and consists of multiple tense non-communicating cysts with no discernible renal cortex. The ultrasound appearances can be diagnostic, but a postnatal DMSA scan is recommended in most centres to confirm lack of function and presence of a normal contralateral kidney. This should not be undertaken prior to 1 month of age, as renal function is inadequate to produce satisfactory images. Over time, many MCDK involute and there is no longer thought to be an increased risk of malignancy or hypertension when compared with the general population.
307
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
Delayed excretion of isotope by enlarged left kidney
Rapid uptake and excretion of isotope by right kidney
Bladder filling
Left kidney – continuing accumulation of isotope even after injection of furosemide
Isotope persists in left kidney on delyed image (60 min post injection)
Normal right kidney rapid excretion of isotope
Figure 2 MAG 3 scan in patient with left sided PUJ obstruction.
There is, however, an increased incidence of abnormality of the contralateral kidney, with studies showing vesicoureteric reflux in 5e28% of cases. There is debate as to whether all children with MCDK should have a micturating cystourethrogram (MCUG). This is an invasive and traumatic test, and with current practice being to restrict antibiotic prophylaxis to more severe cases of reflux, it should only be undertaken if the result
will alter management. Our practice is to undertake MCUG only when ultrasound suggests the possibility of reflux, or where there is a history of a febrile urinary tract infection. Unilateral renal dysplasia/hypoplasia In these conditions, measurement of the serum creatinine in combination with a DMSA scan taken at about 3 months is
Bilateral dilated tortonous ureters with grade 5 vesico-ureteric reflux
Thick-walled trabeculated bladder Dilated posterior urethra Site of posterior urethral valve Figure 3 MCUG in patient with posterior urethral valve associated with bilateral grade 5 vesicoureteric reflux.
PAEDIATRICS AND CHILD HEALTH 24:7
308
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
USS at 4 – 6 weeks post delivery
Ectopic kidney identified
no • • •
If otherwise normal, no need for further follow up
yes
Febrile UTI Contralateral pelvic AP diameter ≥10 mm Ureteric dilatation
no
yes
•
3 months age: • DMSA • Creatinine (abnormal if above 35 µmol/l) • blood pressure • urinalysis
•
Consider MCUG(with antibiotic cover) and/or MAG3 scan Consider prophylaxis
Indications for referral to Paediatric Nephrologist at any stage:
Annual follow up: • Blood pressure • urinalysis
Additionally at 2, 5 and 10 yr follow up: • USS • Creatinine (calculate eGFRΔ)
•
Hypertension
•
Proteinuria >20 mg/mmol creatinine on early morning specimen
•
Lack of compensatory hypertrophy on USS
•
eGFR < 90 ml/min/1.73m2
After 10 years, discharge to GP for lifelong annual: • Blood pressure • Urinalysis Δ From the age of 2, estimated GFR should always be calculated from serum creatinine. The formula is: eGFR = (K x ht (cm))/ creatinine (mmol). K is traditionally 40, but will differ according to method of measurement and should be discussed locally.
Figure 4 Algorithm for management of unilateral MCDK, renal dysplasia, hypoplasia or agenesis with normal contralateral kidney.
helpful to estimate the total renal function and the percentage of function contributed by the dysplastic or hypoplastic kidney. There is an association with vesicoureteric reflux, so there should be a low threshold for undertaking a MCUG. If there are recurrent UTI despite antibiotic prophylaxis, whether to undertake an anti-reflux procedure or simply remove the abnormal kidney and ureter will be a decision informed by the relative function of the affected side. Many urologists consider the benefits of removing a kidney that is contributing less than 10% of total renal function outweigh the risks.
PAEDIATRICS AND CHILD HEALTH 24:7
Hypertension is associated with renal dysplasia, and regular blood pressure measurements are indicated. If there is significantly reduced function (less than 10%) in association with hypertension, removal of the abnormal kidney may be considered and may be curative. Ectopic kidney When there is apparent unilateral renal agenesis, a DMSA may be helpful, as occasionally an ectopic (usually pelvic) kidney is discovered. This provides reassurance in terms of increased
309
Ó 2014 Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEPHROLOGY
and renal scars? A randomized controlled trial. Pediatrics 2008; 121: e1489e94. Phillips D, Watson AR, Collier J. Distress and radiological investigations of the urinary tract in children. Eur J Pediatr 1996; 155: 684e7. Thomas DFM, Rickwood AMK, Duffy PG. Essentials of paediatric urology. 1st Edn. London: Martin Dunitz, 2002. For a general review of congenital nephrotic syndrome: Jalanko H. Congenital nephrotic syndrome. Pediatr Nephrol 2009; 24: 2121e8. For a general review of autosomal recessive polycystic kidney disease: €scher R, Bu €scher AK, Weber S, Hegen B, Vester U, Hoyer PF. Clinical Bu manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes. Pediatr Nephrol Oct 2013; http://dx.doi.org/10.1007/s00467-013-2634-1. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics 2003; 111: 1072e80.
volume of functioning renal tissue, and though ectopic kidneys may be at a slightly greater risk of traumatic damage, they are usually otherwise asymptomatic. Patients with a normal sized ectopic kidney of otherwise normal appearance do not require any specialised follow up.
Summary Improved antenatal screening has increased the numbers of renal abnormalities detected before birth. This can induce considerable anxiety in parents, and expert counselling is required soon after the diagnosis has been made, both in mild and severe cases. All patients require a postnatal ultrasound, and in about 40% of cases this will be normal and the baby can be discharged from follow up. Approximately 35% of babies will have a significant degree of renal tract dilatation. About a third of these have normal follow up investigations, one third have vesicoureteric reflux and one third hold up or obstruction to urinary flow. For cases of vesicoureteric reflux, management centres on prompt diagnosis and treatment of UTI. In mild reflux, antibiotic prophylaxis is not generally recommended but can be considered in individual cases experiencing recurrent infections. There is contention as to whether prophylaxis should be routinely used in higher grades of reflux. Babies with hold up or obstruction to urinary flow (PUJO or VUJO) need close follow up. Management if directed towards detecting whether obstruction is threatening renal health. Most cases can be treated conservatively, with surgery being reserved for the minority of cases developing increasing dilatation, reduction in differential function or symptoms of pain or pyelonephritis. Unilateral abnormalities of renal parenchyma, such as MCDK, dysplasia, hypoplasia or aplasia are present in about 20% of babies with AUTA. The prognosis is generally good, providing the contralateral kidney is normal and undergoes compensatory hypertrophy. Nevertheless, lifelong annual assessments of renal function and urinalysis are recommended because of the small risk of hyperfiltration injury to the ‘normal’ kidney. Serious abnormalities which affect both kidneys, such as posterior urethral valve or bilateral parenchymal abnormality such as bilateral dysplasia are rare but commonly result in renal dysfunction in childhood and require specialist management. A
Practice points C
C
C
C
C
C
C
FURTHER READING Dudley JA, Haworth JM, McGraw ME, Frank JD, Tizard EJ. Clinical relevance and implications of antenatal hydronephrosis. Arch Dis Child Fetal Neonatal Ed 1997; 76: F31e4. Mallik M, Watson AR. Antenatally detected urinary tract abnormalities: more detection but less action. Pediatr Nephrol 2008; 23: 897e904. Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis
PAEDIATRICS AND CHILD HEALTH 24:7
Congenital abnormalities of the kidney and urinary tract are the commonest abnormalities detected by antenatal screening Prognosis should be guarded during antenatal counselling as the outcome may be better or worse than expected. 30% of babies will have normal postnatal scans and the majority of the remainder can be treated conservatively and will have a good prognosis. Many cases of renal tract dilatation can be managed conservatively, but close monitoring of renal health is needed. Prophylactic antibiotics are no longer recommended for mild grades of reflux, and their use in high grade reflux is contentious. Unilateral abnormalities with normal contralateral kidney have an excellent prognosis, but lifelong annual review of blood pressure and urinalysis is recommended because of the long term risk of hyperfiltration injury Babies with high risk features should be jointly managed from the antenatal stage by fetal, neonatal and paediatric nephrology teams.
Acknowledgements The authors would like to thank Dr Andrew Lunn for his helpful comments on this manuscript.
310
Ó 2014 Elsevier Ltd. All rights reserved.