CUA: Antenatal hydronephrosis (2017)

Background

Antenatal hydronephrosis (ANH) is one of the most commonly detected ultrasound (US) findings, affecting 1‒5% of pregnancies
- The majority of ANH in the 3rd trimester is discovered due to US for maternal indications.
- The potential benefit of early detection of urinary tract dilation is to reduce renal damage due to treatment of obstruction and infection. Conversely, many of these antenatally detected cases spontaneously resolve with observation and consequently can be submitted to unnecessary investigations and continued medical follow-up.
Hydronephrosis does not necessary imply urinary tract obstruction
- Hydronephrosis simply refers to dilation of the renal collecting system.
- Definitinon of congenital renal obstruction: impaired urinary drainage, which, if uncorrected, will limit the ultimate functional potential of the developing kidney.
The differential diagnosis of AHN, in order of likelihood, includes:
1. Transient primary hydronephrosis
2. Uretero-pelvic junction obstruction (UPJO)
3. Vesicoureteric reflux (VUR)
4. Uretero-vesical junction obstruction (UVJO)
5. Primary non-obstructive megaureter
6. Ureterocele
7. Ectopic ureter
8. Megacystis (dilated urinary bladder)
- - Includes causes of bladder outlet obstruction due to posterior urethral valves (PUV) and, less commonly, Prune Belly syndrome, megacystis-megaureter syndrome, megacystis-microcolon intestinal hypoperistalsis syndrome, anterior urethral valves, megalourethra, urethral atresia, and cloacal anomalies
- Post-natal resolution has been noted in 25‒50% of AHN cases.
  - Of those persisting postnatally, the majority will be low-grade.
- An association between higher rates of post-natal pathology and severity of HN holds true for most HN diagnoses, with the exception of VUR. VUR rates among patients with mild, moderate, and severe prenatal HN are not significantly different.
Grading

- Descriptors such as mild, moderate, or severe should not be used in isolation, as they are subjective and undefined
- Various grading systems for the severity of AHN exist (3):
  1. Antero-posterior renal pelvic diameter (APD)
    - Simplest form grading
  2. Society of Fetal Ultrasound (SFU) classification
  - - Standard among pediatric urologists

Grade	Ultrasound findings
0	Normal kidney (resolved antenatal hydronephrosis)
1	Pyelectasis
2	Pyelectasis with dilation of 1 or more major calyces (caliectasis)
3	Pyelectasis with dilation of all 3 major calyces
4	Pyelectasis with parenchymal thinning compared to contralateral kidney

- 1. Urinary tract dilation (UTD) classification
  - - Recently proposed by SFU; combines elements of both APD and SFU
    - Uses a 3-point system based on 6 different observations (renal pelvis APD, calyceal dilation, parenchymal thickness/appearance, ureteral dilation, and bladder abnormalities) to stratify patients into 3 risk categories (P1, P2, and P3) based on the most concerning of 6 US variables:
      - UTD P1 (low-risk) with 10‒15 mm renal pelvis APD and central calyceal dilation to UTD P3 with renal pelvis APD >15 mm, peripheral calyceal dilation, parenchymal thinning, ureter dilation, and or bladder abnormality (high-risk).

Definition of the dilated urinary tract

Severity of ANH by antero-posterior renal pelvic diameter

Degree of ANH	Second trimester	Third trimester
Mild	4 to ≤6 mm	7 to ≤8 mm
Moderate	7 to ≤10 mm	9 to ≤15 mm
Severe	>10 mm	≥16 mm

SFU Severity of hydroureteronephrosis (HUN) based on the transverse measure of the distal ureter:
- Grade 1 is <7 mm
- Grade 2 is 7‒10 mm
- Grade 3 is >10 mm.
The dilated fetal bladder or megacystis has been defined based on the formula for fetal bladder sagittal length in mm = gestational age in weeks + 2

Antenatal vs. post-natal follow-up

The frequency of antenatal follow-up of a pregnant mother is left to the discretion of the obstetrician.
Second trimester ANH is often followed up so that progression of severity can be detected and appropriate postnatal follow-up planned
Most centres define significant ANH in the third trimester as APD ≥7 mm
- Although APD >4‒5 mm in the third trimester is considered pyelectasis, the ideal cut-off for routine postnatal screening remains controversial, since high grades of AHN can resolve postnatally and conversely low grades can deteriorate
Indications for referral to a pediatric urologist for antenatal counselling (5):
1. Dilated bladder
2. History of oligohydramnios
3. Severe bilateral hydronephrosis
4. Increased renal cortical echogenicity (hyper-echogenicity)
5. Renal cortical cysts
- These findings raise concern for potential renal failure
While AHN is more common in fetuses with serious chromosomal anomalies, routine karyotyping for all cases of isolated AHN is not recommend. However, this may be considered in the presence of multiple system anomalies.

Postnatal investigations

Physical exam
- Should specifically include verifying the presence of a palpable kidney or bladder, abdominal wall abnormality, signs of spina bifida occulta, a normal introitus in females, and the presence of testicles and a normal urethra in males.
Labs
- Baseline urinalysis
  - Can be useful in the infant follow-up period and when the child is non-verbal and unable to express symptoms of a UTI, although the need for bag specimens introduces a high risk of contamination.
- Serum creatinine
  - Indications (3):
    1. Severe bilateral HN
    2. Abnormal renal echogenicity
    3. Solitary kidney
  - Should be obtained after 2 days to avoid confusion with maternal creatinine.
Imaging
- Renal-bladder US (RBUS)
  - Verbatim (summary section): All significant AHN should be investigated with a postnatal RBUS. Most centres define significant AHN in the third trimester as APD ≥7 mm
    - Verbatim (RBUS section): All children with AHN should have a complete abdominopelvic US, with particular attention to both the kidneys and bladder. [likely meant “significant” ANH rather than "all" patients]
  - The RBUS should include assessment of cranio-caudal length of the kidneys, degree of echogenicity and corticomedullary differentiation, SFU grade of hydronephrosis, maximal APD on transverse axial view of the renal pelvis, diameter of both proximal and distal ureter if dilated, the degree of bladder filling, the detrusor thickness or presence of bladder trabeculation, diverticula, ureterocele, and posterior urethral dilation in males.
  - A full bladder should prompt a period of observation with re-imaging post-void to assess for the capability to empty the bladder and to assess whether the HN improves post-void.
  - Fasting for a RBUS is unnecessary.
  - Timing (see below):
    - Avoid US in the first 2 days of life due to concern of understaging secondary to neonatal oliguria.
    - The acceptable delay in the timing of the first postnatal US is controversial, with the SFU suggesting anywhere from 1‒4 weeks (see Figure 1 from Original Guideline for details, discussed below). In cases where immediate postnatal management is required such as PUV, US should not be delayed.
- Voiding cysto-urethrography (VCUG)
  - The clinical utility of a VCUG in HGHN is to distinguish an obstructive cause of AHN from one due to VUR, not due to concern over UTI
    - On average, 16% of infants with ANH are found to have VUR, with 25% of such cases occurring in the non-dilated, contralateral renal unit.
  - Steps to VCUG
    1. A scout view for assessment of spine anomalies, presence of significant constipation or urinary stones
    2. Catheter is inserted
      - A balloon catheter should not be used, as the balloon can obscure the filling defect characteristic of a ureterocele.
      - The amount of urine removed should be recorded and the urine sent for analysis and culture as indicated.
      - The bladder should be gravity filled until the first void occurs, with recording of the bladder capacity.
    3. Voiding views of the urethra with post-void views of the bladder.
    4. Delayed imaging after the post-void image may be required if there is VUR into a dilated renal pelvis or ureter so as to assess for concomitant UPJO and UVJO
    - A cyclical study with at least two fill and void cycles will increase the detection of VUR.
  - Nuclear cystography is more sensitive than VCUG for VUR with less radiation exposure
  - Indications
    - The AUA guidelines on VUR similarly recommends that VCUG in the neonate with:
      1. High-grade (SFU grade ≥3) hydronephrosis
      2. Hydroureter
      3. An abnormal bladder on ultrasound (late-term prenatal or postnatal)
      4. Develop a UTI on observation
    - VCUG is not necessary in the evaluation of isolated LGHN (SFU 1‒2) with normal renal parenchyma and symmetric renal size
    - Any infant with suspected bladder outlet obstruction (e.g., PUV) should have an urgent VCUG. The following should raise suspicious for bladder outlet obstruction (7):
      1. Dilated posterior urethra
      2. Distended bladder
      3. Thick or trabeculated bladder
      4. History of oligohydramnios
      5. Severe bilateral hydronephrosis
      6. Increased renal cortical echogenicity (hyper-echogenicity)
      7. Renal cortical cysts
- Diuretic renography
  - MAG3 diuretic renogram is test of choice for the assessment of the function of a hydronephrotic kidney as it permits assessment of both the differential renal function (DRF) and the drainage time.
    - A dimercaptosuccinic acid (DMSA) study can be considered to establish early split function in cases of neonates or premature infants, since the DRF in this study is not influenced by an immature GFR.
  - The diuretic renogram should include a report of the DRF, which can vary from 45‒55%; the cortical transit time, which is normal up to 5 minutes; the half-time; and the shape of the curve.
  - Test results can be influenced by
    - Poor renal function (single kidney glomerular filtration rate [GFR] <15 ml/min)
    - Poor hydration
    - Massively dilated collecting system
    - Full bladder
    - Dilated distal ureter
  - Renograms can be performed at any age, as long as they are used as a baseline study for serial comparison.
  - Indications
    - APD >15 mm or HGHN (SFU 3-4) with VCUG was negative for VUR to identify other potential causes of hydronephrosis (such as UPJO, UVJO)
    - Not necessary in the evaluation of isolated LGHN (SFU 1‒2) with normal renal parenchyma and symmetric renal size
Other
- Additional studies are sometimes necessary to further elucidate the precise cause of AHN, which, because of their invasive nature, are reserved for only select cases.
- Percutaneous antegrade pyelography or endoscopic retrograde pyelography can be useful when multiple levels of obstruction are suspected, such as combined UPJO and UVJO.
- Cystoscopy can help for evaluation of ectopic ureters and ureteroceles as can magnetic resonance urography (MRU). MRU can be especially helpful with the abnormal anatomy found in duplication anomalies, renal ectopy and renal fusion anomalies

Continuous antibiotic prophylaxis (CAP)

The role of CAP initiated at birth is controversial
CAP may be of benefit in (4):
1. HGHN (SFU 3-4)
2. Females with ANH
3. Uncircumcised males with ANH
4. Cases with dilated ureter or bladder abnormality
Commonly used prophylaxes in the neonate include:
1. Amoxicillin
2. Cephalexin
3. Trimethoprim
- Trimethoprim is contraindicated in premature infants and age <6 weeks (CW12 p442)
- TMP/SMX should NOT be used age <6-8 weeks because of the respective risk of kernicterus. (CW12 p443/513)
- Nitrofurantoin should NOT be used age <3 months because of the risk of hemolytic anemia.

Follow-up protocols

Based on severity of hydronephrosis
- See Figure 1 from Original Guideline
- High-grade hydronephrosis (SFU Grades 3 and 4) or APD >15 mm
  - Initial post-natal RBUS
    - Should be done as soon as feasible after day 2 of life (most centres recommend within 2 weeks of life) as this represents the cohort most likely to require surgery and to experience UTI.
    - If the postnatal US reveals persistent high-grade hydronephrosis, these cases should be referred to a pediatric urologist for immediate consultation.
      - Bilateral HGHN requires more urgent consultation.
  - Additional investigations
    - Patients should have a VCUG
      - MAG3 renal scan should be done if the VCUG is negative for VUR
  - These cases are most likely to benefit from CAP
  - In the absence of any pathology requiring immediate intervention, repeat US and MAG3 should be performed within 3 months, although a repeat MAG3 is optional if the first exam is normal. If improvement is not seen, close follow-up should continue to at least 18 months of age, by which time most childhood UPJO becomes apparent.
- For cases with antenatal APD 10‒15 mm, the SFU grading is suggested to clarify which follow-up protocol should be used
- Low-grade hydronephrosis (SFU Grade 1 and 2) or APD <10 mm
  - Initial post-natal RBUS
    - Timing open to debate; most physicians will obtain an US within the first months of life and a follow-up can be obtained 6 months later.
      - In the absence of deterioration, follow-up US can then be performed on an annual basis.
  - Additional investigations
    - VCUG and MAG3 are not required
  - CAP is unnecessary
  - The majority of such cases improve by age 2. Since the majority of congenital UPJO progresses to pyeloplasty by 18 months of age, continue follow-up to at least until age 2.
    - There is controversy on the need for follow-up beyond 2 years of age in patients who have persistent LGHN.
- SFU Grade 0
  - Up to 50% of ANH can resolve at birth and is referred to as SFU Grade 0 HN.
  - SFU guidelines recommend a repeat US within the first month of life.
    - Many centres will discharge the patient after a normal post-natal US, since the majority of late or recurrent HN are symptomatic and can be counselled as such.
  - In patients with a history of mild to moderate fetal hydronephrosis and a normal post-partum ultrasound (obtained at 1-2 months), additional evaluations are unnecessary.
  - In patients with a history of moderate to severe fetal hydronephrosis and a normal post-partum ultrasound, additional evaluations are necessary.
    - The presence of ureteral dilation on the pre-natal ultrasound has been found to be associated with a significant increased risk for neonatal UTIs and high-grade vesicoureteral reflux despite a normal post-partum renal ultrasound.
    - A neonatal VCUG is recommended if ureteral dilation is found on the fetal ultrasound.

Indications for surgery in obstructive HN and HUN

Appropriate counselling of families should include a discussion of the risks of observation vs. immediate surgery.
Strong indications for reconstructive surgery include (2):
1. Loss of DRF of >5% on serial renography
2. Worsening HN with worsening drainage times on renography
- - In older children, flank pain or vomiting are also suggestive of obstruction, especially if exacerbated by fluid intake. Hypertension and renal calculi can rarely be signs of obstruction.
Relative indications for surgery (5):
1. UTI
2. Low DRF on initial renogram
3. Palpable giant HN
4. Concern over non-compliance with follow-up imaging protocols
5. Family preference in cases of persistent HGHN requiring repeated renographic evaluation
Threshold for surgical intervention is lowered in cases of solitary kidney or bilateral HGHN

Questions

What is the differential diagnosis of ANH in order of likelihood?
Describe the SFU grading for ANH

In the third trimester, what antero-posterior renal pelvic diameter is considered mild, moderate, and severe antenatal hydronephrosis?
When is post-natal evaluation of antenatal hydronephrosis generally indicated?
What are the indications for a referral to a pediatric urologist for antenatal counselling?
In which patients should a serum creatinine be obtained as part of the post-natal evaluation?
What imaging findings on ultrasound warrant a VCUG in the work-up of ANH?
When should post-natal US be performed in patients with ANH?
What are the indications for diuretic renography?
Which patients with ANH may benefit from continuous antibiotic prophylaxis? Which antibiotics are commonly used? Which should be avoided and why?
What are the indications for surgery in obstructive hydronephrosis?

Answers

What is the differential diagnosis of ANH in order of likelihood?
1. Transient primary hydronephrosis
2. Uretero-pelvic junction obstruction (UPJO)
3. Vesicoureteric reflux (VUR)
4. Uretero-vesical junction obstruction (UVJO)
5. Primary non-obstructive megaureter
6. Ureterocele
7. Ectopic ureter
8. Megacystis (dilated urinary bladder)
Describe the SFU grading for ANH

Grade	Ultrasound findings
0	Normal kidney (resolved antenatal hydronephrosis)
1	Pyelectasis
2	Pyelectasis with dilation of 1 or more major calyces (caliectasis)
3	Pyelectasis with dilation of all 3 major calyces
4	Pyelectasis with parenchymal thinning compared to contralateral kidney

In the third trimester, what antero-posterior renal pelvic diameter is considered mild, moderate, and severe antenatal hydronephrosis?
- Mild: 7-8mm
- Moderate 9-15mm
- Severe: >15
When is post-natal evaluation of antenatal hydronephrosis generally indicated?
- When third trimester US shows APD ≥ 7mm
What are the indications for a referral to a pediatric urologist for antenatal counselling?
1. Dilated bladder
2. Severe bilateral AHN
3. Renal cortical hyper-echogenicity
4. Renal cortical cysts
5. History of oligohydramnios
In which patients should a serum creatinine be obtained as part of the post-natal evaluation?
1. Severe bilateral HN
2. Solitary kidney
3. Abnormal renal echogenicity
What imaging findings on ultrasound warrant a VCUG in the work-up of ANH?
1. Dilated posterior urethra
2. Thick or trabeculated detrusor
3. Dilated bladder
4. Severe bilateral HN
5. Increased renal cortical echogenicity
6. Renal cortical cysts
7. History of oligohydramnios
When should post-natal US be performed in patients with ANH?
- If HGHN (SFU 3-4) or APD >15mm, then within first 2 weeks
- If LGHN (SFU 1-2) or APD 7-10mm, then within first 3 months
What are the indications for diuretic renography?
- HGHN (SFU Grades 3 and 4) or APD >15 mm whose VCUG was negative for VUR
Which patients with ANH may benefit from continuous antibiotic prophylaxis? Which antibiotics are commonly used? Which should be avoided and why?
- CAP may be of benefit in:
1. 1. Grades 3 and 4 HN
  2. Females with AHN
  3. Uncircumcised males with AHN
  4. Cases with dilated ureter or bladder abnormality
- Commonly used prophylaxes in the neonate include amoxicillin, cephalexin, and trimethoprim.
- TMP/SMX and nitrofurantoin should NOT be used in the neonate because of the respective risk of kernicterus and hemolytic anemia, respectively.
What are the indications for surgery in obstructive hydronephrosis?
1. Loss of DRF of >5% on serial renography (absolute)
2. Worsening HN with worsening drainage times on renography (absolute)
3. UTI (relative)
4. Low DRF on initial renogram (relative)
5. Palpable giant HN (relative)
6. Concern over non-compliance with follow-up imaging protocols (relative)
7. Family preference in cases of persistent HGHN requiring repeated renographic evaluation (relative)