Renal and genital

Question 1

What is Henoch-Schonlein purpura?

Answer 1

• A small vessel vasculitis, characterised by the classic tetrad:
  rash,
  abdominal pain,
  arthritis/arthralgia and
  glomerulonephritis

Question 2

What is the aetiology of Henoch-Schonlein purpura?

Answer 2

Genetic predisposition and environmental trigger leads to increased circulating IgA and disrupted IgG synthesis

• IgA and IgG interact to product IgA-containing complexes
• These are deposited within affected organs (kidney, GI tract, skin) → inflammatory response with vasculitis

Often preceded by an URTI, esp streptococcal infections

• May also occur after drugs (e.g. penicillin)

Question 3

What is the epidemiology of Henoch-Schonlein purpura?

Answer 3

• Usually occurs in 3-10yo;
  
  • 50% occur in <5yo
• M>F

Question 4

What are the signs and symptoms of Henoch-Schonlein purpura?

Answer 4

• Rash
  
  • Occurs in all patients – mandatory for diagnosis (+ one other symptom)
  • Symmetrically distributed over buttocks, extensor surfaces of arms and legs, and ankles; trunk is usually spared
  • May initially be urticarial, rapidly becoming maculopapular and purpuric
  • Palpable
  • May recur over several wks
• Joint pain (80%)
  
  • Esp knees and ankles, periarticular oedema
  • There is no long-term damage and symptoms resolve before the rash goes
• Colicky abdominal pain (50%)
  
  • Often associated with nausea and vomiting
  • GI involvement can cause haematemesis and melaena; intussusception may occur
• Renal involvement (80%)
  
  • Microscopic or macroscopic haematuria, proteinuria, RBC casts
  • Varies in severity
    
    • Mild: haematuria (microscopic or macroscopic), mild proteinuria
    • Severe: rapidly progressive nephritis, nephrotic syndrome and renal failure

Question 5

What is the Ix for Henoch-Schonlein purpura?

Answer 5

• Usually clinical diagnosis (with urine dip)
• Urine dip
  
  • In all patients with suspected HSP
  • May show RBCs, proteinuria or casts
• 24hr urine for protein
  
  • May be raised due to renal involvement
• Bloods:
  
  • Serum U&Es and creatinine
    
    • If abnormalities on urinalysis
    • Elevated creatinine indicates renal impairment or failure
  • Serum IgA
    
    • May be elevated (not a specific test for HSP)
  • Coagulation studies
    
    • To exclude other causes à should be normal
• Skin/renal biopsy
  
  • If unusual presentation
  • Shows IgA deposition
• Abdo USS
  
  • If severe abdo pain → look for intussusception

Question 6

What is the Mx of Henoch-Schonlein purpura?

Answer 6

Symptomatic management:

• For joint pain and abdominal pain:
  
  • Paracetamol, ibuprofen
• For oedema/scrotal involvement and severe abdominal pain:
  
  • Oral corticosteroids (prednisolone)
  • Rest, hydration, elevation of affected limb
  • If abdo pain is very severe à surgical referral (possible intussusception)

For nephrotic range proteinuria or declining GFR:

• Nephrology referral
• Corticosteroids
  
  • IV methylprednisolone (pulse dosing) for 3 days; followed by 4 months oral prednisolone
  • To reverse the inflammatory process and prevent irreversible glomerular injury
• May need renal biopsy to determine severity and prognosis
• If rapidly progressing nephritis à immunosuppressants (cyclophosphamide or azathioprine), plasmapheresis

Follow-up:

• All children followed up for 1yr
  
  • To detect persisting haematuria or proteinuria (10%)
• Long-term follow-up
  
  • For children with persistent renal involvement or required treatment (to monitor for complications)

Question 7

What are the complications and prognosis of Henoch-Schonlein purpura?

Answer 7

Complications:

• Renal impairment and deterioration of function → may progress to end-stage renal failure (rare)
  
  • RFs are heavy proteinuria, oedema, HTN and deteriorating renal function
• GI haemorrhage & intussusception
• CNS & ocular complications
• Orchitis

Prognosis

• Children with mild renal involvement usually make a complete recovery
• 1/3 have recurrence within 4 months, but usually milder

Question 8

What is a UTI

Answer 8

Symptomatic bacterial infection involving the lower urinary tract (cystitis), upper urinary tract (pyelonephritis) or both

Question 9

Which organisms cause UTIs?

Answer 9

Most common organism is E. coli

Also caused by

• Klebsiella,
• Proteus,
  
  • M>F (under prepuce), predisposes to phosphate stones by splitting urea to ammonia
• Pseudomonas,
  
  • usually in children with congenital abnormality of urinary tract, stones or catheters
• Streptococcus faecalis
• Staphylococcus saprophyticus

Question 10

Which host factors predispose to UTI?

Answer 10

• Renal or urinary tract abnormalities
• Incomplete bladder emptying
  
  • Caused by infrequent voiding (resulting in bladder enlargement), obstruction by a loaded rectum from constipation, neuropathic bladder, vesicoureteric reflux
• Vesicoureteric reflux

Question 11

Summarise vesico-uteric reflux

Answer 11

• Familial developmental anomaly of the vesicoureteric junctions
• The ureters are displaced laterally and enter directly into the bladder rather than at an angle, with shortened or absent intramural course
• May also occur with bladder pathology, e.g. neuropathic bladder, urethral obstruction, or temporarily after a UTI
• Severity varies from reflux into the lower end of an undilated ureter during micturition, to the most severe form with reflux during bladder filling and voiding, with a distended ureter, renal pelvis and clubbed calyces
  
  • Mild VUR usually resolves spontaneously and is of no clinical significance
  • Severe forms cause intrarenal reflux
• VUR-associated ureteric dilation can lead to:
  
  • Urine returning to the bladder from the ureters after voiding à incomplete bladder emptying à infection
  • Pyelonephritis if there is intrarenal reflux (acute then chronic)
  • Bladder voiding pressure transmitted to the renal papillae à renal damage if voiding pressures are high
• Infection may destroy renal tissue à leads to scarred, shrunken, poorly-functioning segment of kidney (reflux nephropathy)
  
  • If bilateral and severe à CKD and HTN

Question 12

What are the RFs for a UTI?

Answer 12

age <1yo,

female,

uncircumcised boys in the 1^st year of life,

previous UTI,

voiding dysfunction,

VUR,

sexual activity,

obstructive anomalies,

constipation,

diarrhoea

Question 13

What are the Sx of a UTI?

Answer 13

• Upper UTI: bacteriuria with pyrexia >38⁰C or loin pain with pyrexia <38⁰C
• Lower UTI: bacteriuria with no systemic symptoms
• Infants/young children:
  
  • Pyrexia
  • Vomiting
  • Lethargy
  • Irritability
  • Poor feeding/failure to thrive
  • Offensive urine, haematuria
• Older children:
  
  • Dysuria, frequency, urgency
  • Abdominal pain and loin tenderness
  • Secondary enuresis
  • Fever +/- rigors
  • Offensive/cloudy urine, haematuria

Question 14

What are the Ix for a UTI

Answer 14

Urine sample should be tested in all infants with unexplained fever >38⁰C

• Urine dip
  
  • Nitrites are very likely to indicate UTI (but some children with UTI are nitrite negative); leukocytes are present in other febrile illnesses (so not specific for UTI)
  • Leukocyte esterase and nitrite positive à suggests UTI
    
    • If leukocyte esterase negative and nitrite positive à can still treat as UTI if clinically suspicious (do culture)
    • If leukocyte esterase positive and nitrite negative à less likely to be UTI; still do culture if clinically suspicious
    • If both are negative à UTI unlikely; can still do culture if clinically suspicious
      
      • May be negative in infants (as haven’t mounted a detectable immune response)
• Urine microscopy and culture
  
  • In all children <3yo with suspected UTI, and if urine dip is negative but still suspicious of UTI
  • Microscopy shows >4 WBC/high-power field or any bacteria; culture of >10⁵ CFU of a single organism per millilitre in a properly collected specimen gives 90% probability of infection
  • Culture is gold standard
  • Growth of mixed organisms is usually contamination
• Bloods (if febrile/systemically unwell)
  
  • FBC, CRP, U&Es

Question 15

What are atypical and recurrent UTIs?

Answer 15

• Atypical UTIs include:
  
  • seriously ill/septicaemia,
  • poor urine flow,
  • abdominal/bladder mass,
  • raised creatinine,
  • failure to respond to antibiotics within 48hrs,
  • atypical (non-E.coli) organisms
• Recurrent UTIs:
  
  • ≥2 UTI with acute pyelonephritis,
  • or 1 episode with acute pyelonephritis + one episode with cystitis,
  • or 3 episodes of cystitis

Question 16

What are the Ix for atypical or reccurrent UTI?

Answer 16

• USS:
  
  • For atypical or recurrent UTIs, or <6mo
  • To look for structural abnormalities and urinary obstruction, renal defects
• DMSA (dimerceptosuccinic acid) scan:
  
  • For atypical or recurrent UTIs, 4-6 months after infection
  • To diagnose pyelonephritis or renal scarring
• Voiding cystourethrogram:
  
  • To evaluate presence and degree of VUR
• MCUG:
  
  • If urethral obstruction is suspected

Question 17

What is the Mx of UTI?

Answer 17

Treatment of UTI depends on age and severity:

• <3mo with suspicion of UTI or if seriously ill:
  
  • Refer to hospital
  • IV antibiotics (e.g. ampicillin + gentamycin) for 5-7d
    
    • Then oral prophylaxis can be started
• >3mo with acute pyelonephritis/upper UTI:
  
  • Consider severity when deciding treatment setting
    
    • More severe if: younger, vomiting, inadequate fluid intake
  • 2-4d of IV antibiotics (e.g. ceftriaxone, ampicillin + gentamycin) followed by 7-10d of oral antibiotics
  • Oral antibiotics (e.g. cefixime, co-amoxiclav) for 7d
  • Antibiotic choice is adjusted according to sensitivity on urine culture
• Children with cystitis/lower UTI:
  
  • Oral antibiotics (e.g. trimethoprim, nitrofurantoin, amoxicillin) for 3d
  • Antibiotic choice is adjusted according to sensitivity on urine culture

Question 18

What is the follow-up of children with recurrent UTIs, renal scarring or reflux?

Answer 18

• Urine dip should be done with any nonspecific illness, and sent for MC&S if suggestive of UTI
• Low-dose antibiotic prophylaxis (trimethoprim)
  
  • Given at least until child is out of nappies (in congenital abnormalities); may be given long-term
• Anti-VUR surgery if there is progression of scarring with ongoing VUR
• Regular monitoring of BP, urinalysis for proteinuria (suggests CKD) and renal growth/function if bilateral defects

Question 19

What is the conservative (preventative Mx of UTI)?

Answer 19

• High fluid intake to produce a high urine output
• Regular voiding
• Ensure complete bladder emptying à encourage child to try a second time to empty bladder after 1-2min
• Treatment/prevention of constipation
• Good perianal hygiene
• Antibiotic prophylaxis

Question 20

What are the complications and prognosis of UTI?

Answer 20

Complications:

• Sepsis
• Chronic pyelonephritis
• CKD (if scarring is bilateral)
• HTN

Prognosis is usually good

• There is risk of recurrent infection after 1^st UTI
• Progression of renal dysfunction is unlikely (even in patients with urinary tract comorbidity)

Question 21

What is enuresis?

Answer 21

Micturition that occurs at an inappropriate or socially unacceptable time or place

Primary nocturnal enuresis:

• Enuresis during sleep (bedwetting)

Daytime enuresis:

• Lack of bladder control during the day in a child old enough to be continent (over 3-5yo)

Secondary (onset) enuresis:

• Loss of previously achieved urinary continence

Question 22

Aetiology of enuresis?

Answer 22

Nocturnal enuresis:

• Essentially caused by a mismatch between nocturnal urine production and functional bladder capacity, compounded by an inability to wake à bedwetting
• Most children are dry during the day before they are dry at night
• Small children need freedom from stress and a measure of parental approval to learn night-time continence
• 2/3 of children have an affected 1^st degree relative
• May also be associated with developmental, attention or learning difficulties (e.g. ADHD)
• Organic causes are the same as those for secondary enuresis (but are rare)

Daytime enuresis:

• May be caused by:
  
  • Lack of attention to bladder sensation
    
    • A manifestation of a developmental or psychogenic problem, or may occur in otherwise normal children who are preoccupied
  • Detrusor instability (sudden urge to void due to detrusor contractions)
  • Bladder neck weakness
  • Neuropathic bladder
    
    • Bladder is enlarged and fails to empty properly; has an irregular thick wall
    • Associated with spina bifida and other neurological complications
  • UTI (rare without other symptoms)
  • Constipation
  • Ectopic ureter
    
    • Causes constant dribbling; child is always damp
• Nocturnal enuresis is also usually present

Secondary enuresis:

• May be due to:
  
  • Emotional upset (most common)
  • UTI
  • Faecal retention
    
    • If severe enough to reduce bladder volume and case bladder neck dysfunction
  • Polyuria from an osmotic diuresis in DM or renal concentrating disorder (e.g. sickle cell disease, CKD, DI (central or nephrogenic))

Question 23

Epidemiology of enuresis?

Answer 23

Median age of dryness during the day is 3.5yrs, and during the night is 4yrs

Nocturnal enuresis:

• Very common if infrequent
• >2 nights/wk in 6% 5yo and 1% 10yo

Question 24

Signs and symptoms of enuresis?

Answer 24

• Bedwetting or incontinence during the day
• May have signs of underlying cause:
  
  • May have evidence of neuropathic bladder à distended bladder, may have abnormal perineal sensation and anal tone, abnormal leg reflexes and gait, sensory loss in S2, S3 and S4
  • Girls who are dry at night but wet on getting up are likely to have urine from an ectopic ureter opening into the vagina

Question 25

Ix of enuresis?

Answer 25

• Nocturnal enuresis:
  
  • Ix only indicated if bed wetting is of recent onset, occurs during the day, or if there are features of UTI, DM or ill health à see secondary enuresis
• Daytime enuresis:
  
  • Urine MC&S
  • Other Ix depend on likely cause
    
    • USS
      
      • May show bladder pathology, incomplete bladder emptying, thickening of bladder wall
    • Urodynamic studies
    • Spine X-ray
      
      • May show abnormal vertebral anatomy
    • MRI
      
      • To confirm/exclude spinal defect, e.g. tethering of spinal cord
• Secondary enuresis:
  
  • Urine dip
    
    • For infection, glycosuria and proteinuria
  • Measure osmolality of an early morning urine sample
    
    • To assess urine concentrating ability
    • Rarely, a formal water deprivation test may be needed

Renal tract USS

Question 26

Mx of enuresis?

Answer 26

Nocturnal enuresis:

• Education and lifestyle changes: (1^st line)
  
  • Explain to child and parent that the problem is common and beyond conscious control
  • Don’t punish the child
  • Address excessive/insufficient fluid intake and abnormal toileting patterns
  • Star charts:
    
    • Child is praised and a star is awarded for agreed behaviour helping to change the sheets, rather than dry nights
    • Wet beds are treated in a matter-of-fact way; child is not blamed
  • Treatment is only considered at >5yo (usually only started at 7yo)
• Enuresis alarm: (2^nd line)
  
  • Sensor, usually placed in pants or under the child, which sounds an alarm when it becomes wet à wakes the child, gets out of bed to pass urine, returns and helps to remake a wet bed before going back to sleep
  • Takes several weeks to achieve dryness but is effective in most cases (as long as child is motivated and procedure is followed fully)
  • 1/3 relapse after a few months à repeat treatment usually produces lasting dryness
• Desmopressin: (3^rd line)
  
  • Synthetic ADH
  • May be used if >7yo and alarm unsuccessful or unacceptable, or short-term relief is needed (e.g. holidays, sleepovers)
  • Restrict fluid intake after use
  • May need to be continued for 3-6 months
  • Can be combined with alarm (4^th line)
• Imipramine (TCA): (5^th line)
  
  • Rarely used à considered in ADHD patients who may also be prescribed it for ADHD
• Self-help groups:
  
  • Advice and assistance to parents and health professionals
  • E.g. ERIC, the Children’s Bowel and Bladder Charity

Daytime enuresis:

• Treat underlying neurological/anatomical cause (if there is one)
• If neuro/anatomical causes is excluded:
  
  • Star charts
  • Bladder training
    
    • Education, rigorous scheduling of diet and voiding habits, and psychological support
    • Most helpful for daytime enuresis but has been used for nocturnal enuresis
  • Pelvic floor exercises
  • Enuresis alarm (if lack of attention to bladder sensation)
  • Anticholinergics, e.g. oxybutynin
    
    • If other measures fail

Management of secondary enuresis depends on the cause

Question 27

Complications and prognosis of enuresis?

Answer 27

Complications:

• Shame, low-self esteem
• Frustration for family

Long-term resolution is almost inevitable à very rare in adults

• Short-term recurrence is common

Question 28

What is acute glomulonephritis?

Answer 28

Inflammation of the glomeruli and nephrons, caused by a range of disorders

Question 29

Aetiology of acute glomulonephritis?

Answer 29

Glomerular inflammation leads to 2 consequences:

1. Loss of barrier function à proteinuria (mild to nephrotic syndrome) and haematuria (mild to macrocytic)
2. Loss of filtering capacity à reduced excretion, so accumulation of waste products (AKI)

Causes are classified based on histology:

• Post-streptococcal glomerulonephritis:
  
  • Secondary to group A beta-haemolytic Strep à glomerular infiltration of inflammatory cells and proliferation of endothelial and mesangial cells
  • Presents with nephritic syndrome 1-12 weeks after URTI (serotype 12) or skin infection (serotype 49)
  • Rare in developed countries but common in developing world
  • Diagnosed by evidence of recent Strep infection (culture, raised ASO/anti-DNAse B titres) and low C3 levels that return to normal after 3-4wks
  • Almost all children recover without treatment
• Vasculitis:
  
  • HSP (see separate section)
  • SLE
  • Wegener granulomatosis (granulomatosis with polyangiitis)
• Mesangiocapillary glomerulonephritis (aka membranoproliferative glomerulonephritis)
  
  • Proliferation of mesangial cells, increase in mesangial matrix and thickening of glomerular BM
  • Causes nephrotic syndrome or nephritic syndrome in children and young adults
  • Low C3
  • 50% develop end-stage renal failure within 10yrs
• Mesangial proliferative nephritis:
  
  • Aka IgA nephropathy when seen with IgA deposition
  • Often presents with macroscopic haematuria; may be associated with URTI; can present with nephrotic syndrome
  • Progression to end-stage renal disease is rare
  • The renal lesion in HSP is similar (or thought to be a variant)
• Goodpastures syndrome (aka anti-basement membrane disease):
  
  • Due to autoantibodies against type IV collagen in the glomerular BM
  • Presents with haematuria and haemoptysis
  • Causes rapidly-progressive glomerulonephritis
• Minimal change disease (see nephrotic syndrome)
  
  • Fusion of the epithelial cell foot processes on the outside of the glomerular BM (on EM)
  • Causes steroid-sensitive nephrotic syndrome with normal renal function, normal BP, normal C3
• Focal segmental glomerulosclerosis
  
  • Common cause of nephrotic syndrome in older children and younger adults
  • Some of the glomeruli show segmental scarring and foot process fusion
  • May be associated with haematuria, HTN and impaired renal function
  • Progresses to end-stage renal failure in 50% over many years
• Membranous nephropathy:
  
  • Widespread thickening of the glomerular basement membrane; granular deposits of immunoglobulin and complement on immunofluorescence
  • Usually idiopathic (but may be secondary to SLE and Hep B); may precede SLE
  • Causes nephrotic syndrome
  • Progresses to end-stage renal failure in 30-50%
• Alport syndrome:
  
  • Familial nephritis (X-linked recessive)
  • Progresses to end-stage CKD by early adult life

Associated with nerve deafness and ocular defects

Question 30

Epidemiology of acute glomulonephritis?

Answer 30

Depends on cause

Question 31

Ix for acute glomerulonephretis?

Answer 31

• Urine dipstick
  
  • For protein, check for microscopic haematuria
• Urine MC&S (exclude UTI)
• 24hr urine protein
  
  • >50mg/kg/d
  • May be difficult to collect in younger children à can use spot urine protein:creatinine ratio instead
  • Nephrotic-range proteinuria varies by age and size of the child
• Bloods:
  
  • U&Es, creatinine
  • Serum albumin (typically <30g/L – normal is 35)
  • Serum lipids (hyperlipidaemia is a complication)
• Ix for cause:
  
  • C3 and C4 levels: C3 is low in membranoproliferative glomerulonephritis, postinfectious glomerulonephritis and SLE
  • Hep B and C screen, HIV, malaria screen (if foreign travel)
  • Antistreptolysin O or anti-DNAse B titres and throat swab
  • IgA antibodies, antinuclear antibodies (SLE)
  • Renal USS
  • Renal biopsy:
    
    • Only in older children with haematuria, HTN, renal impairment and steroid-resistant

Question 32

Mx of acute glomerulonephretis?

Answer 32

Depends on the type, severity and complications

General:

• Monitor haematuria and proteinuria
• Monitor fluids; treat oedema with fluid restriction and diuretics
• Monitor and correct electrolyte balance
• Monitor and correct acid-base imbalances
• Antihypertensive therapy (ACEi)

Possible use of steroids/immunosuppressive agents (HSP, minimal change disease)

Treat underlying cause if possible

Specialist referral

Question 33

Complications and prognosis of acute glomerulonephretis?

Answer 33

Complications:

• HTN à encephalopathy, seizures, end-organ damage, cerebral haemorrhage
• Nephrotic syndrome (and its complications – thrombosis, infection, etc.)
• End-stage renal failure
  
  • May occur with any cause of acute glomerulonephritis (rare in some types)
  • Uraemia, metabolic acidosis, electrolyte abnormalities, fluid overload
  • Renal biopsy to diagnose; treatment with immunosuppression and plasma exchange

Prognosis depends on type

Question 34

What is nephrotic syndrome?

Answer 34

Clinical syndrome with a triad of proteinuria, hypoalbuminaemia and oedema

Question 35

Aetiology of nephrotic syndrome?

Answer 35

Structural damage to the glomerular membrane leads to proteinuria

• This leads to hypoalbuminaemia (secondary to proteinuria and increased breakdown of albumin in kidney)
• Hypoalbuminaemia leads to decreased intravascular osmotic pressure à oedema

Steroid-sensitive nephrotic syndrome (aka minimal change disease):

• In 90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy
• Does not progress to CKD
• Association with atopy
• Features strongly suggesting steroid-sensitive: age 1-10yo, no macroscopic haematuria, normal BP, normal complement levels, normal renal function

Steroid-resistant nephrotic syndrome:

• Primary causes:
  
  • Focal segmental glomerulosclerosis
  • Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis)
  • Membranous nephropathy
• Secondary causes:
  
  • Infection (HIV, Hep B/C, malaria)
  • SLE, HSP
  • Bee stings

Congenital nephrotic syndrome:

• Rare autosomal recessive disease; more common in Finland and consanguineous families
• Presents in first 3 months of life

High mortality due to complications of hypoalbuminaemia

Question 36

Epidemiology of nephrotic syndrome?

Answer 36

Uncommon à about 1/10,000 children worldwide

Steroid-sensitive nephrotic syndrome: peak age 2-4yo; M>F; more common in Asian children

Question 37

Symptoms and signs of nephrotic syndrome?

Answer 37

• Periorbital oedema (esp on waking)
  
  • Often the earliest sign
• Scrotal or vulval, leg and ankle oedema
• Ascites
• Anorexia, lethargy
• Oliguria, haematuria
• HTN

Question 38

Ix of nephrotic syndrome?

Answer 38

• Urine dipstick
  
  • For protein, check for microscopic haematuria
• Urine MC&S (exclude UTI)
• 24hr urine protein
  
  • >50mg/kg/d
  • May be difficult to collect in younger children à can use spot urine protein:creatinine ratio instead
  • Nephrotic-range proteinuria varies by age and size of the child
• Bloods:
  
  • U&Es, creatinine
  • Serum albumin (typically <30g/L – normal is 35)
  • Serum lipids (hyperlipidaemia is a complication)
• Ix for cause:
  
  • C3 and C4 levels: C3 is low in membranoproliferative glomerulonephritis, postinfectious glomerulonephritis and SLE
  • Hep B and C screen, HIV, malaria screen (if foreign travel)
  • Antistreptolysin O or anti-DNAse B titres and throat swab
  • Renal biopsy:
    
    • Only in older children with haematuria, HTN, renal impairment and steroid-resistant

Question 39

Mx of nephrotic syndrome?

Answer 39

Symptomatic management of oedema:

• Low-sodium diet
• Diuretics
• Daily weight and fluid balance to monitor

Steroid-sensitive nephrotic syndrome:

• Oral corticosteroids (prednisolone)
  
  • 60mg/m² for 4wks; then 40mg/m² on alternate days for 4wks; then weaned/stopped
  • If no response to steroids after 4-6wks à may have a more complex diagnosis
    
    • Do renal biopsy (in steroid-sensitive renal histology is normal on light microscopy but there is fusion of podocytes on EM à therefore called minimal-change disease)
• Parental urine testing for relapses
• If relapses:
  
  • Involve paediatric nephrologist
  • May need steroid-sparing agents (e.g. cyclophosphamide, mycophenolate mofetil, rituximab)

Steroid-resistant nephrotic syndrome:

• Refer to paediatric nephrologist
• ACEi for HTN
• Genetic testing

Penicillin prophylaxis to reduce infection risk; TED stockings to reduce thrombosis risk

Question 40

Complications and prognosis of nephrotic syndrome?

Answer 40

Complications:

• Hypovolaemia
  
  • During the initial phase of oedema, the intravascular compartment may become depleted
  • There is peripheral vasoconstriction and urinary sodium retention
    
    • Low urinary sodium (<10mmol/L) and high RBC packed cell volume suggest hypovolaemia
  • Urgent treatment with IV normal saline
  • May cause respiratory compromise à if severe give 20% albumin infusion and furosemide
• Thrombosis:
  
  • There is a hypercoagulable state due to urinary loss of ATIII, thrombocytosis, increased clotting factor synthesis and increased blood viscosity from raised Hct
• Infection
  
  • Risk of infection with encapsulated bacteria (esp Pneumococcus), spontaneous peritonitis
  • Give pneumococcal and influenza vaccines to children in relapse
  • Treat chickenpox and singles with acyclovir
• Hypercholesterolaemia:
  
  • Inverse correlation with serum albumin
• SEs of corticosteroid therapy if relapsing steroid-sensitive
• End-stage renal failure (in steroid-resistant)

Steroid-sensitive nephrotic syndrome:

• Urine usually becomes free of protein after 11d
• 1/3 resolve directly; 1/3 have infrequent relapses, 1/3 relapse frequently and become steroid-dependent

Steroid-resistant nephrotic syndrome:

• Focal segmental glomerulosclerosis: 30% progress to end-stage renal-failure in 5yrs; 20% respond to cyclophosphamide, cyclosporin, tacrolimus or rituximab
• Mesangiocapillary glomerulonephritis: decline in renal function over many years
• Membranous nephropathy: most remit spontaneously within 5yrs

NB causes of proteinuria:

• Orthostatic proteinuria (only found when upright during the day; further Ix not needed)
• Glomerular abnormalities (minimal change disease, glomerulonephritis, familial nephritides)
• Increased glomerular filtration pressure
• Reduced renal mass in CKD
• HTN

Question 41

What is acute glomerulonephritis?

Answer 41

Inflammation of the glomeruli and nephrons, caused by a range of disorders

Question 42

What are the types of acute glomerulonephritis?

Answer 42

Glomerular inflammation leads to 2 consequences:

1. Loss of barrier function à proteinuria (mild to nephrotic syndrome) and haematuria (mild to macrocytic)
2. Loss of filtering capacity à reduced excretion, so accumulation of waste products (AKI)

Causes are classified based on histology:

• Post-streptococcal glomerulonephritis:
  
  • Secondary to group A beta-haemolytic Strep à glomerular infiltration of inflammatory cells and proliferation of endothelial and mesangial cells
  • Presents with nephritic syndrome 1-12 weeks after URTI (serotype 12) or skin infection (serotype 49)
  • Rare in developed countries but common in developing world
  • Diagnosed by evidence of recent Strep infection (culture, raised ASO/anti-DNAse B titres) and low C3 levels that return to normal after 3-4wks
  • Almost all children recover without treatment
• Vasculitis:
  
  • HSP (see separate section)
  • SLE
  • Wegener granulomatosis (granulomatosis with polyangiitis)
• Mesangiocapillary glomerulonephritis (aka membranoproliferative glomerulonephritis)
  
  • Proliferation of mesangial cells, increase in mesangial matrix and thickening of glomerular BM
  • Causes nephrotic syndrome or nephritic syndrome in children and young adults
  • Low C3
  • 50% develop end-stage renal failure within 10yrs
• Mesangial proliferative nephritis:
  
  • Aka IgA nephropathy when seen with IgA deposition
  • Often presents with macroscopic haematuria; may be associated with URTI; can present with nephrotic syndrome
  • Progression to end-stage renal disease is rare
  • The renal lesion in HSP is similar (or thought to be a variant)
• Goodpastures syndrome (aka anti-basement membrane disease):
  
  • Due to autoantibodies against type IV collagen in the glomerular BM
  • Presents with haematuria and haemoptysis
  • Causes rapidly-progressive glomerulonephritis
• Minimal change disease (see nephrotic syndrome)
  
  • Fusion of the epithelial cell foot processes on the outside of the glomerular BM (on EM)
  • Causes steroid-sensitive nephrotic syndrome with normal renal function, normal BP, normal C3
• Focal segmental glomerulosclerosis
  
  • Common cause of nephrotic syndrome in older children and younger adults
  • Some of the glomeruli show segmental scarring and foot process fusion
  • May be associated with haematuria, HTN and impaired renal function
  • Progresses to end-stage renal failure in 50% over many years
• Membranous nephropathy:
  
  • Widespread thickening of the glomerular basement membrane; granular deposits of immunoglobulin and complement on immunofluorescence
  • Usually idiopathic (but may be secondary to SLE and Hep B); may precede SLE
  • Causes nephrotic syndrome
  • Progresses to end-stage renal failure in 30-50%
• Alport syndrome:
  
  • Familial nephritis (X-linked recessive)
  • Progresses to end-stage CKD by early adult life
  • Associated with nerve deafness and ocular defects

Question 43

Epidemiology of acute glomerulonephritis?

Answer 43

Depends on cause

Question 44

Signs and symptoms of acute glomerulonephritis?

Answer 44

There is increased glomerular cellularity so decreased blood flow → decreased GFR → leads to:

• Decreased urine output
• HTN → may cause seizures
• Oedema (characteristically periorbital)
• Haematuria & proteinuria
• There is a spectrum of disease, ranging from asymptomatic to nephrotic and nephritic syndromes
  
  • Nephrotic syndrome: heavy proteinuria, hypoalbuminaemia and oedema
  • Nephritic syndrome: haematuria (micro or macroscopic), proteinuria, fall in GFR, salt and water retention, HTN
• Other symptoms depend on cause

Question 45

Ix for acute glomerulonephritis?

Answer 45

• Urine dipstick
  
  • For protein, check for microscopic haematuria
• Urine MC&S (exclude UTI)
• 24hr urine protein
  
  • >50mg/kg/d
  • May be difficult to collect in younger children à can use spot urine protein:creatinine ratio instead
  • Nephrotic-range proteinuria varies by age and size of the child
• Bloods:
  
  • U&Es, creatinine
  • Serum albumin (typically <30g/L – normal is 35)
  • Serum lipids (hyperlipidaemia is a complication)
• Ix for cause:
  
  • C3 and C4 levels: C3 is low in membranoproliferative glomerulonephritis, postinfectious glomerulonephritis and SLE
  • Hep B and C screen, HIV, malaria screen (if foreign travel)
  • Antistreptolysin O or anti-DNAse B titres and throat swab
  • IgA antibodies, antinuclear antibodies (SLE)
  • Renal USS
  • Renal biopsy:
    
    • Only in older children with haematuria, HTN, renal impairment and steroid-resistant

Question 46

Mx of AKI?

Answer 46

Depends on the type, severity and complications

General:

• Monitor haematuria and proteinuria
• Monitor fluids; treat oedema with fluid restriction and diuretics
• Monitor and correct electrolyte balance
• Monitor and correct acid-base imbalances
• Antihypertensive therapy (ACEi)

Possible use of steroids/immunosuppressive agents (HSP, minimal change disease)

Treat underlying cause if possible

Specialist referral

Question 47

Complications and prognosis AKI?

Answer 47

Complications:

• HTN à encephalopathy, seizures, end-organ damage, cerebral haemorrhage
• Nephrotic syndrome (and its complications – thrombosis, infection, etc.)
• End-stage renal failure
  
  • May occur with any cause of acute glomerulonephritis (rare in some types)
  • Uraemia, metabolic acidosis, electrolyte abnormalities, fluid overload
  • Renal biopsy to diagnose; treatment with immunosuppression and plasma exchange

Prognosis depends on type

Question 48

Causes of proteinuria?

Answer 48

• Orthostatic proteinuria (only found when upright during the day; further Ix not needed)
• Glomerular abnormalities (minimal change disease, glomerulonephritis, familial nephritides)
• Increased glomerular filtration pressure
• Reduced renal mass in CKD
• HTN

Question 49

What is nephrotic syndrome?

Answer 49

Clinical syndrome with a triad of:

• proteinuria,
• hypoalbuminaemia and
• oedema

Question 50

Aetiology of nephrotic syndrome?

Answer 50

Structural damage to the glomerular membrane leads to proteinuria

• This leads to hypoalbuminaemia (secondary to proteinuria and increased breakdown of albumin in kidney)
• Hypoalbuminaemia leads to decreased intravascular osmotic pressure à oedema

Steroid-sensitive nephrotic syndrome (aka minimal change disease):

• In 90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy
• Does not progress to CKD
• Association with atopy
• Features strongly suggesting steroid-sensitive: age 1-10yo, no macroscopic haematuria, normal BP, normal complement levels, normal renal function

Steroid-resistant nephrotic syndrome:

• Primary causes:
  
  • Focal segmental glomerulosclerosis
  • Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis)
  • Membranous nephropathy
• Secondary causes:
  
  • Infection (HIV, Hep B/C, malaria)
  • SLE, HSP
  • Bee stings

Congenital nephrotic syndrome:

• Rare autosomal recessive disease; more common in Finland and consanguineous families
• Presents in first 3 months of life
• High mortality due to complications of hypoalbuminaemia

Question 51

Epidemiology of nephrotic syndrome?

Answer 51

Uncommon → about 1/10,000 children worldwide

Steroid-sensitive nephrotic syndrome: peak age 2-4yo; M>F; more common in Asian children

Question 52

Signs and symptoms of nephrotic syndrome?

Answer 52

• Periorbital oedema (esp on waking)
  
  • Often the earliest sign
• Scrotal or vulval, leg and ankle oedema
• Ascites
• Anorexia, lethargy
• Oliguria, haematuria
• HTN

Question 53

Ix of nephrotic syndrome?

Answer 53

• Urine dipstick
  
  • For protein, check for microscopic haematuria
• Urine MC&S (exclude UTI)
• 24hr urine protein
  
  • >50mg/kg/d
  • May be difficult to collect in younger children à can use spot urine protein:creatinine ratio instead
  • Nephrotic-range proteinuria varies by age and size of the child
• Bloods:
  
  • U&Es, creatinine
  • Serum albumin (typically <30g/L – normal is 35)
  • Serum lipids (hyperlipidaemia is a complication)
• Ix for cause:
  
  • C3 and C4 levels: C3 is low in membranoproliferative glomerulonephritis, postinfectious glomerulonephritis and SLE
  • Hep B and C screen, HIV, malaria screen (if foreign travel)
  • Antistreptolysin O or anti-DNAse B titres and throat swab
  • Renal biopsy:
    
    • Only in older children with haematuria, HTN, renal impairment and steroid-resistant

Question 54

Mx of nephrotic syndrome?

Answer 54

Symptomatic management of oedema:

• Low-sodium diet
• Diuretics
• Daily weight and fluid balance to monitor

Steroid-sensitive nephrotic syndrome:

• Oral corticosteroids (prednisolone)
  
  • 60mg/m² for 4wks; then 40mg/m² on alternate days for 4wks; then weaned/stopped
  • If no response to steroids after 4-6wks à may have a more complex diagnosis
    
    • Do renal biopsy (in steroid-sensitive renal histology is normal on light microscopy but there is fusion of podocytes on EM à therefore called minimal-change disease)
• Parental urine testing for relapses
• If relapses:
  
  • Involve paediatric nephrologist
  • May need steroid-sparing agents (e.g. cyclophosphamide, mycophenolate mofetil, rituximab)

Steroid-resistant nephrotic syndrome:

• Refer to paediatric nephrologist
• ACEi for HTN
• Genetic testing

Penicillin prophylaxis to reduce infection risk; TED stockings to reduce thrombosis risk

Question 55

Complications and prognosis of nephrotic syndrome?

Answer 55

Complications:

• Hypovolaemia
  
  • During the initial phase of oedema, the intravascular compartment may become depleted
  • There is peripheral vasoconstriction and urinary sodium retention
    
    • Low urinary sodium (<10mmol/L) and high RBC packed cell volume suggest hypovolaemia
  • Urgent treatment with IV normal saline
  • May cause respiratory compromise à if severe give 20% albumin infusion and furosemide
• Thrombosis:
  
  • There is a hypercoagulable state due to urinary loss of ATIII, thrombocytosis, increased clotting factor synthesis and increased blood viscosity from raised Hct
• Infection
  
  • Risk of infection with encapsulated bacteria (esp Pneumococcus), spontaneous peritonitis
  • Give pneumococcal and influenza vaccines to children in relapse
  • Treat chickenpox and singles with acyclovir
• Hypercholesterolaemia:
  
  • Inverse correlation with serum albumin
• SEs of corticosteroid therapy if relapsing steroid-sensitive
• End-stage renal failure (in steroid-resistant)

Steroid-sensitive nephrotic syndrome:

• Urine usually becomes free of protein after 11d
• 1/3 resolve directly; 1/3 have infrequent relapses, 1/3 relapse frequently and become steroid-dependent

Steroid-resistant nephrotic syndrome:

• Focal segmental glomerulosclerosis: 30% progress to end-stage renal-failure in 5yrs; 20% respond to cyclophosphamide, cyclosporin, tacrolimus or rituximab
• Mesangiocapillary glomerulonephritis: decline in renal function over many years
• Membranous nephropathy: most remit spontaneously within 5yrs

Question 56

What are the causes of proteinuria?

Answer 56

• Orthostatic proteinuria (only found when upright during the day; further Ix not needed)
• Glomerular abnormalities (minimal change disease, glomerulonephritis, familial nephritides)
• Increased glomerular filtration pressure
• Reduced renal mass in CKD
• HTN

Question 57

What is AKI?

Answer 57

A sudden, potentially reversible, reduction in renal function

Question 58

Aetiology of AKI?

Answer 58

Causes are classified into prerenal, renal and postrenal

• Prerenal (most common):
  
  • Caused by:
    
    • Hypovolaemia: haemorrhage, GI losses (gastroenteritis, DKA), burns, diarrhoea, septic shock, nephrotic syndrome
    • Cardiac failure: severe coarctation, hypoplastic L heart, myocarditis
    • Hypoxia: pneumonia, RDS
• Intrinsic renal:
  
  • Caused by:
    
    • Vascular:
      
      • HUS (triad of AKI, MAHA and thrombocytopenia due to verocytotoxin-producing E. coli O157:H7)
      • Vasculitis, embolus, renal vein thrombosis
    • Tubular:
      
      • Acute tubular necrosis (80% of intrinsic renal causes)
        
        • Due to circulatory compromise – due to pre-renal AKI, or nephrotoxic drugs (paracetamol, aminoglycosides)
      • Ischaemic, toxic, obstructive
    • Glomerular:
      
      • Acute glomerulonephritis
    • Interstitial:
      
      • Acute interstitial nephritis (infection, drugs (NSAIDs, frusemide, penicillin)
      • Pyelonephritis
• Postrenal:
  
  • Caused by urinary obstruction
    
    • Neuropathic bladder, posterior urethral valves, blocked catheter, stones
  • Obstruction results in increased intratubular pressure à tubular ischaemia and atrophy

AKI results in failure to maintain homeostasis of fluid (oliguria, volume overload), electrolytes (hyperkalaemia) and acid-base (metabolic acidosis)

• Disease spectrum varies from mild renal impairment to severe renal failure

Question 59

Epidemiology of AKI?

Answer 59

Prerenal AKI is most common in children

HUS and multisystem failure (causing ATN) are the most common causes of renal AKI in children

Question 60

Signs and symptoms of AKI?

Answer 60

• Oliguria (0.5ml/kg/hr)
• Anorexia, nausea and vomiting
• Oedema
• SOB (due to volume overload)
• Signs of the cause, e.g. sepsis
• Acute-on-chronic renal failure is suggested by:
  
  • Growth failure
  • Anaemia
  • Renal osteodystrophy

Question 61

Ix of AKI?

Answer 61

• Urinalysis
  
  • For blood, protein (glomerulonephritis), glucose (interstitial nephritis)
  • Microscopy for casts (glomerulonephritis)
  • Osmolality and Na levels (low Na in pre-renal as body tries to retain volume; high in intrinsic)
• Bladder catheterisation
  
  • Significant urine volume if bladder outlet obstruction; small volume if impaired urine production or higher level obstruction
• Bloods:
  
  • U&Es (high urea, high creatinine, high K)
  • Blood gases (metabolic acidosis)
  • FBC (for cause – anaemia suggests blood loss, high WCC suggests infection)
  • Blood cultures (if infection suspected)
  • Blood film (RBC fragmentation in HUS)
• Renal USS:
  
  • To identify obstruction
  • Small kidneys suggest CKD, large bright kidneys suggest acute
• ECG: may show electrolyte abnormalities (e.g. hyperkalaemia)
• CXR: signs of pulmonary oedema
• Renal biopsy
  
  • If cause is unknown

Question 62

Mx of AKI?

Answer 62

Close monitoring and supportive management:

• Circulation and fluid balance, urine output (catheterise)
• U&Es, ECG
• Stop nephrotoxic drugs
• Aim for euvolaemia (give fluids or fluid restrict/diuretics as needed)
• Correct acidosis, hyperkalaemia and hyperphosphataemia
  
  • Metabolic acidosis: sodium bicarbonate
  • Hyperphosphataemia: calcium carbonate, dietary restriction
  • Hyperkalaemia: calcium gluconate if ECG changes, salbutamol (nebulised or IV), calcium exchange resin, glucose and insulin, dietary restriction, dialysis

Prerenal:

• ABCDE approach, fluids, circulatory support
• Treat underlying cause
• If severe, consult nephrologist because dialysis may be needed

Renal:

• High-calorie, normal protein feed to decrease catabolism, uraemia and hyperkalaemia
• Treat underlying condition
  
  • Rapidly progressive glomerulonephritis may need treatment with immunosuppression
• If severe, consult nephrologist because dialysis may be needed

Postrenal:

• Relief of obstruction by bladder catheterisation or surgery
• If severe, consult nephrologist because dialysis may be needed

Dialysis:

• Indicated in AKI when there is:
  
  • Failure of conservative management
  • Severe hyperkalaemia, hyponatraemia or hypernatraemia, metabolic acidosis (not controlled with medical management)
  • Pulmonary oedema or severe HTN due to volume overload
  • Multisystem failure

May be peritoneal dialysis or haemodialysis

Question 63

Complications and prognosis of AKI?

Answer 63

Complications:

• Uraemia
  
  • Causes anorexia, nausea, vomiting, encephalopathy, arrhythmias, pericarditis
• Volume overload
  
  • Causes pulmonary oedema and peripheral oedema
  • Treat by sitting up, high-flow oxygen, venous vasodilator (diamorphine) and furosemide IV
• Hyperkalaemia:
  
  • ECG changes: tall tented T waves, absent P waves, wide QRS, increased PR interval, bradycardia
  • Treat with 10ml 10% calcium gluconate (cardioprotective), IV insulin and glucose and salbutamol nebulisers. If patient is acidotic can give bicarbonate (also drives K into cells)
• Hyperphosphataemia:
  
  • Treated with dietary restrictions
• Metabolic acidosis
• Chronic renal failure and end stage renal disease

Prognosis depends on the cause

Best prognosis if after pre-renal causes, HUS or ATN

Question 64

What is CKD?

Answer 64

Progressive loss of renal function, characterised by decreased GFR and persistently raised urea and creatinine

Question 65

What are the causes of CKD?

Answer 65

There is progressive fibrosis of the glomeruli, tubules and small vessels à renal scarring à decreased function

Causes of CKD:

• <5yo:
  
  • Congenital abnormalities: hypoplasia, obstruction (posterior urethral valves), malformations
• >5yo:
  
  • Hereditary disorders: Alport syndrome (thickened glomerular basement membrane), autosomal recessive polycystic kidney disease
  • Acute glomerulonephritis (all causes can cause CKD)
  • Vesicoureteral reflux
  • Systemic disease (HSP, SLE)

Question 66

What are the 5 stages of CKD?

Answer 66

1. eGFR >90ml/min per 1.73m²
   
   • Normal renal function but structural abnormality or persistent haematuria or proteinuria
2. eGFR 60-89ml/min per 1.73m²
   
   • Mildly reduced renal function, asymptomatic
3. eGFR 30-59ml/min per 1.73m²
   
   • Moderately reduced renal function, renal osteodystrophy
4. eGFR 15-29ml/min per 1.73m²
   
   • Severely reduced renal function with metabolic derangements and anaemia à make plans for renal replacement therapy
5. eGFR <15ml/min per 1.73m²
   
   • End stage renal failure à renal replacement therapy required
   • Much less common in children than adults

Question 67

Epidemiology of CKD?

Answer 67

Congenital and familial causes are more common in childhood than acquired disease

Question 68

Symptoms and signs of CKD?

Answer 68

• Antenatal diagnosis (for many congenital abnormalities)
• Stage 1-3 tends to be asymptomatic
  
  • Incidental finding of proteinuria
  • Unexplained normochromic, normocytic anaemia
• Stage 4 and 5 presents with:
  
  • Anorexia and lethargy
  • Polydipsia and polyuria
  • Faltering growth
  • Bony deformities from renal osteodystrophy (renal rickets) – seen in stage 3 too
  • HTN
  • Acute-on-chronic renal failure (precipitated by infection or dehydration)

Question 69

Ix for CKD?

Answer 69

• Urinalysis
  
  • Haematuria, proteinuria
  • 24hr collection for protein
• Bloods:
  
  • U&Es (high urea, high creatinine, high K)
  • Gases (metabolic acidosis)
  • Determine GFR
• Renal ultrasound
  
  • May show structural malformations
• Renal biopsy
  
  • To determine the cause (e.g. glomerulonephritis)
• Abdominal X-ray/CT/MRI
• Complement components and autoantibody screening to detect autoimmune causes (see glomerulonephritis)

Question 70

Mx for CKD?

Answer 70

Aims to prevent symptoms and metabolic abnormalities, allow normal growth and development, and preserve residual renal function

Conduct management in specialist paediatric nephrology centre with MDT approach

Diet:

• Calorie supplementation if needed (NG/gastrostomy)
• Protein intake should be enough to maintain growth, but prevent accumulation of toxic by-products

Prevention of renal osteodystrophy:

• Phosphate retention and hypocalcaemia due to decreased activation of vitamin D lead to secondary hyperparathyroidism à causes osteitis fibrosis cystica and osteomalacia
• To prevent renal osteodystrophy:
  
  • Phosphate restrict (e.g. decrease dairy products)
  • Calcium carbonate (phosphate binder)
  • Activated vitamin D supplements

Control of salt and water balance and acidosis:

• Many children with CKD caused by structural malformations and renal dysplasia have an obligatory loss of salt and water
• Give salt supplements and free access to water
• Bicarbonate supplements to prevent acidosis

Anaemia:

• Due to reduced production of EPO and circulation of metabolites that are toxic to the BM
• Give SC EPO

Hormonal abnormalities:

• There is growth hormone resistance (high GH levels but poor growth)
  
  • Recombinant GH improves growth for up to 5yrs (unknown if this improves final height)
• Delayed puberty and subnormal pubertal growth spurt
  
  • Common in stage 4 and 5

Dialysis and transplantation:

• Optimum management is transplantation à difficult in very small children; minimum weight of 10kg must be reached to avoid renal vein thrombosis
• Immunosuppression is needed
• Ideally, child is transplanted before dialysis is needed
  
  • If this is not possible à dialysis
  • Peritoneal dialysis (either cycling overnight using a machine (continuous cycling dialysis) or manual exchanges over 24hrs (continuous ambulatory peritoneal dialysis) can be done by parents at home
  • Alternatively haemodialysis is used
    
    • In hospital 3x/wk à more disruptive to family life and school

Question 71

Complications and prognosis of CKD?

Answer 71

Complications are discussed in management (anaemia, faltering growth etc.)

CKD is progressive and irreversible

Survival after transplantation is high à 95% 1^st yr graft survival; 90% for 5yrs

• Better survival if living donor (rather than deceased)

Question 72

What is nephroblastoma?

Answer 72

A malignant tumour of the kidney

Aka Wilms tumour

Question 73

Aetiology of nephroblastoma?

Answer 73

Originates from embryonal renal tissue

• It is an undifferentiated mesodermal tumour of the intermediate cell mass (primitive renal tubules and mesenchymal cells)

May be inherited or occur sporadically

• Various genes are implicated, e.g. WT1 gene (11p13), WT2 gene (11p15)
• Risk is increased with various syndromes (e.g. Down’s) and urogenital abnormalities (hypospadias, cryptorchidism)
• But only 10% are associated with congenital malformations or have positive FHx

Most common sites for metastasis are lungs, regional lymph nodes, liver and bone

Question 74

Epidemiology of nephroblastoma?

Answer 74

Most common renal tumour of childhood (but still uncommon)

Usually presents <5yo (80%); very rare after 10yo

15% have metastatic disease at presentation

Question 75

Signs and symptoms of nephroblastoma?

Answer 75

• Large abdominal/flank mass +/- abdominal distension
• Usually otherwise-well
• Haematuria
• Less common presentation:
  
  • Abdominal pain, anorexia
  • Anaemia (haemorrhage into mass)
  • HTN

Question 76

Ix for nephroblastoma?

Answer 76

• Urine dip (microscopic or macroscopic haematuria, protein)
• Bloods:
  
  • FBC: may show anaemia (normocytic normochromic or due to IDA)
  • U&Es and creatinine: normal or impaired renal function (increased creatinine)
  • LFTs: abnormal if liver mets
  • Serum calcium: elevated if bone mets or elevated PTH
  • Serum albumin: low in unwell children
• USS
  
  • Shows intrinsic renal mass
• CT/MRI with and without contrast
  
  • Confirms USS findings and defines extent of tumour
  • Enough for presumptive diagnosis, but histology is needed for definitive diagnosis
• Staging tests
  
  • CXR, CT/MRI chest
• Definitive diagnosis is with nephrectomy or open biopsy (if tumour is unresectable)
• Consider genetic studies

Question 77

Mx for nephroblastoma?

Answer 77

MDT approach

• Referral to specialist centre
• Paediatric surgeons, pathologists, paediatric oncologists etc.

Nephrectomy

• In all patients
• Tumour is staged histologically (histology gives definitive diagnosis)
• Subsequent treatment is planned according to surgical and pathological findings

Chemotherapy

• May be given pre and postoperatively, or postoperatively only

Radiotherapy

• For advanced disease à flank or whole abdomen irradiation

If bilateral disease (5%) management needs to be particularly careful to preserve as much renal function as possible

Question 78

Complications and prognosis of nephroblastoma?

Answer 78

Complications:

• Anaemia
• Acquired vWD (<10%)
• Renal failure (may occur in patients with bilateral disease)
• Complications of chemotherapy: pancytopenia, febrile neutropenia, constipation, hepatotoxicity, cardiotoxicity, infertility, secondary malignancies (radiotherapy and chemo)

Prognosis is good → 80% cured

• If favourable histology (grade 1-2) à >90% 5yr survival
• Cure rate for metastatic disease at presentation (15%) is 60%

Relapse has poor prognosis

Question 79

What are congenital abnormalities of the renal tract?

Answer 79

Abnormalities in the development of any structure in the urinary tract

Question 80

What is the aetiology of congenital abnormalities of the renal tract?

Answer 80

They are potentially important because they may:

• Be associated with abnormal renal development or function (CKD)
• Predispose to infection
• Cause urinary obstruction which needs surgical treatment

Question 81

What is the aetiology of congenital abnormalities of the renal tract?

Answer 81

They are potentially important because they may:

• Be associated with abnormal renal development or function (CKD)
• Predispose to infection
• Cause urinary obstruction which needs surgical treatment

Question 82

What are the types of congenital abnormalities of the renal tract?

Answer 82

• Renal agenesis:
  
  • Absence of both kidneys
  • Causes severe oligohydramnios àfoetal compression à Potter’s syndrome
    
    • Potter’s syndrome:
      
      • Intrauterine compression of the foetus from oligohydramnios caused by lack of foetal urine
      • Low-set ears, beaked nose, prominent epicanthic folds and downwards slant to eyes, pulmonary hypoplasia, limb deformities
  • Fatal (stillborn or dies soon after birth from respiratory failure)
• Multicystic dysplastic kidney:
  
  • Non-functioning structure with large cysts, no renal tissue and no connection with the bladder
  • 50% will have involuted by 2yo; nephrectomy indicated if it remains large
  • If bilateral, they cause Potter syndrome (because they produce no urine)
• Other causes of large cystic kidneys are:
  
  • Autosomal recessive polycystic kidney disease (ARPKD)
  • Autosomal dominant polycystic kidney disease (ADPKD)
    
    • 1 in 1000
    • Causes HTN in childhood and renal failure in late adulthood
  • Tuberous sclerosis
  • In these disorders some or normal renal function is maintained, but both kidneys are always affected (in contrast to a multicystic dysplastic kidney)
• Pelvic kidney or horseshoe kidney:
  
  • Pelvic kidney is due to abnormal migration; horseshoe kidney is when the lower poles are fused
  • May predispose to obstruction of urinary drainage
• Duplex system:
  
  • Varies from simply a bifid renal pelvis, to complete division with 2 ureters
  • These ureters often have abnormal drainage à ureter from the lower pole often refluxes and ureter from the upper pole may drain ectopically into the urethra or vagina, or may prolapse into the bladder (uterocoele) and obstruct urine flow
• Bladder exstrophy:
  
  • Failure of fusion of the infraumbilical midline structures à exposed bladder mucosa
  • If due to absence or severe deficiency of anterior wall muscles (prune-belly syndrome), it is often associated with a large bladder and large ureters (megacystis-megaureter) and cryptorchidism
• Obstruction to urine flow:
  
  • May occur at the pelviureteric or vesicoureteric junction, at the bladder neck (due to neuropathic bladder) or at the posterior urethra in a boy (due to posterior urethral valves)
  • Urinary obstruction results in dilation of the urinary tract proximal to the site of obstruction à hydroureters and hydronephrosis, thickened bladder wall with diverticulae
  • May ultimately lead to a dysplastic kidney à small, poorly functioning, may contain cysts
    
    • If very severe and bilateral à Potter syndrome

Question 83

Signs and symptoms of congenital abnormalities of the renal tract?

Answer 83

• Usually diagnosed antenatally
• Other symptoms depend on the cause, e.g. oligohydramnios in bilateral renal agenesis

Question 84

Ix for congenital abnormalities of the renal tract?

Answer 84

• Antenatal USS diagnosis is most common
  
  • Allows early planning and treatment à opportunity to minimise/prevent progressive renal damage
  • Careful attention to amount of amniotic fluid
• Postnatal:
  
  • USS
  • Intravenous urogram (allows visualisation of anomalies that are not well seen on USS)
  • DMSA, MCUG, MAG3

Question 85

Mx for congenital abnormalities of the renal tract?

Answer 85

Antenatal:

• Counselling
• Karyotyping if appropriate

Postnatal treatment:

• Start prophylactic antibiotics at birth (to prevent UTI)
• Catheter (if obstruction suspected (e.g. posterior urethral valves))
• Symptom control (antihypertensives, calcium supplements, phosphate binders)
• Dialysis (for renal failure)
• Surgery:
  
  • Treat the problem
  • E.g. nephrectomy in multicystic dysplastic kidney/non-functioning kidney; removal of posterior urethral valves, etc.

Question 86

Complications and prognosis of congenital abnormalities of the renal tract?

Answer 86

Complications (depend on cause):

• Hypertension
• Renal osteodystrophy
• UTIs
• Calculi

Prognosis depends on the cause

Question 87

What is an inguinal hernia?

Answer 87

Protrusion of abdominal contents through the fascia of the abdominal wall, through the internal inguinal canal

Question 88

Aetiology of inguinal hernia?

Answer 88

Usually caused by a persistently patent processus vaginalis

• In embryological development, the structures that are found in the scrotum in a boy (testes, vas and blood vessels) or labium in a girl (attachment of the round ligament of the uterus) pass through the abdominal wall as they migrate downwards and pick up layers corresponding to those of the abdominal wall
  
  • In a boy these make up the coverings of the spermatic cord
  • In boys and girls there is a remnant of peritoneal invagination, the processus vaginalis (normally obliterates by term)
    
    • If the processus vaginalis remains patent and in continuity with the abdomen, abdominal contents can become a hernia

Hernias emerge from the deep inguinal ring and pass through the inguinal canal (due to failure of inguinal canal to close)

• Therefore they are usually indirect (can be direct in premature babies where the tissues are weak)
• Direct hernias protrude directly through a weakness in the posterior wall of the inguinal canal

The contents of the hernia may become incarcerated (irreducible)

• Strangulation can occur à visceral contents of the hernia become twisted à bowel obstruction and compromised blood supply à infarction, damage to testes
• Risk of incarceration is much higher in infants than older children
• In girls, sometimes an ovary can be incarcerated within a hernia

Question 89

RFs of inguinal hernia?

Answer 89

• prematurity,
• male,
• FHx,
• undescended testes

Question 90

Epidemiology of inguinal hernia?

Answer 90

• Common (5% boys);
• even more common in premature babies

Question 91

Signs and symptoms of inguinal hernia?

Answer 91

• Reducible lump in the groin which may extend into the scrotum or labium
• Usually asymptomatic
• May be intermittent à visible during straining
• If incarcerated:
  
  • Tender lump; irreducible; oedema
  • Infant may be irritable, may vomit

Question 92

Ix for inguinal hernia?

Answer 92

• Clinical diagnosis
• USS if there is doubt

Question 93

Mx of inguinal hernia?

Answer 93

Surgery (heriotomy):

• Herniotomy: ligation and division of processus vaginalis
• If reducible:
  
  • Outpatient referral for surgical repair (should be prompt to reduce incarceration risk, esp if neonate)
• If non-reducible:
  
  • Most can be reduced by ‘taxis’ before surgery (manual reduction with IV morphine)
    
    • Then repair 48hrs later (after oedema has settled)
  • If manual reduction fails à emergency surgery

Question 94

Complications and prognosis of inguinal hernia?

Answer 94

Complications:

• Incarceration (50% if <1yo) à infarcted testes/ovary, intestinal injury
• After herniotomy:
  
  • Recurrence (1%)
  • Damage to bladder, vas deferens, testicular vessels (testicular atrophy)
  • Wound infection

Prognosis is excellent with surgical repair

Question 95

What is testicular torsion?

Answer 95

Urological emergency caused by the twisting of the testicle on the spermatic cord

Question 96

Aetiology of testicular torsion?

Answer 96

Urological emergency caused by the twisting of the testicle on the spermatic cord

Question 97

RFs for testicular torsion?

Answer 97

Undescended testis, ‘clapper bell’ testis, trauma

• ‘Clapper bell’ testis: when testis lies transversely on its attachment to the spermatic cord)
  
  • Testis is normally covered by the tunica vaginalis (layer of peritoneum) which has superior and inferior attachments
  • In this deformity, both attachments occur superior to the testicle à increased risk of torsion because testicle is freely mobile within the tunica

Question 98

Epidemiology of testicular torsion?

Answer 98

Most common in post-pubertal boys

In newborns it usually presents at birth (and is believed to be perinatal)

Question 99

Signs and symptoms of testicular torsion?

Answer 99

• Sudden-onset scrotal pain
  
  • May be intermittent à suggests periods of torsion and spontaneous de-torsion
  • Usually no relief upon elevation of the scrotum
• Redness and oedema
• Nausea and vomiting
• May present with groin/abdo pain à must examine the testes in a boy presenting with sudden onset pain in the groin, abdomen or scrotum

Question 100

Ix for testicular torsion?

Answer 100

• Clinical diagnosis à don’t delay surgery
• If diagnosis is unclear à USS and Doppler scans
  
  • To assess for torsion and assess blood flow

Question 101

Mx for testicular torsion?

Answer 101

Emergency → must be treated early to lower risk of complications

Analgesia (morphine)

Emergency surgical exploration

• The contralateral testis is also fixed to the posterior wall (due to increased risk of contralateral torsion)
• In neonates with unilateral torsion:
  
  • Surgery is not always emergency because the testicle is unlikely to be salvaged anyway
  • Semi-elective surgery minimises anaesthetic risk

Question 102

Complications and prognosis of testicular torsion?

Answer 102

Complications:

• Subfertility (due to ischaemia and necrosis)
  
  • After 10hrs, irreversible damage is likely; after >12hrs, necrosis has usually occurred
  • If bilateral testicular loss à impaired pubertal development
• Recurrence (if contralateral testis is not fixed)
• Cosmetic deformity
• Psychological implications

If treatment is started within 6hrs, the testis usually remains viable

In perinatal torsion, testicular loss is almost inevitable

Question 103

What is phimosis?

Answer 103

Phimosis: inability to retract the foreskin proximally over the glans penis

• Can be congenital (normal up to the age of puberty) or acquired (pathologic)

Question 104

What happens to the foreskin as the child grows?

Answer 104

The foreskin (aka prepuce):

• Normal foreskin does not retract in infancy; 1% boys >16yo have a non-retractile foreskin
  
  • Mean age of 1^st foreskin retraction is 10yrs
• The foreskin develops adherent to the underlying glans
• Protects the meatal squamous epithelium (in an environment when urine can cause inflammation)
• When traction is applied (gently) to a normal foreskin, the skin at the preputial opening everts (even if it doesn’t open up completely)
  
  • A foreskin that is pathologically non-retractile will not do this à differentiates a normal foreskin that is simply non-retractile from one which is problematic

Question 105

Causes of phimsosis?

Answer 105

• Balanitis xerotica obliterans (BXO) – aka male lichen sclerosus
  
  • Most common cause (95%)
  • Chronic inflammatory skin condition
  • Keratinisation of the tip of the foreskin causes progressive scarring which can extend onto the glans/meatus/urethra à foreskin cannot be retracted
  • Foreskin was usually normally retractile earlier in childhood
• Rarer causes are repeated infections (balanoposthitis), trauma, repeated forced retraction of non-retractile foreskin

Question 106

Epidemiology of phimosis?

Answer 106

BXO usually affects older boys (>9yo) and young adults

Question 107

Symptoms of phimosis?

Answer 107

• BXO:
  
  • Irritation
  • Dysuria, haematuria
  • Local infection
  • On examination:
    
    • Foreskin is white, fibrotic and the preputial tip is scarred
    • Often difficult to visualise the meatus (can also be scarred)

Question 108

Ix for phimosis?

Answer 108

clinical diagnosis

Question 109

Mx of phimosis?

Answer 109

Phimosis if <12yo, congenital or physiological:

• Reassurance

BXO/phimosis in >12yo:

• Topical corticosteroids
  
  • 4-6wks (can be repeated once)
• Circumcision (if doesn’t respond to steroids)

Question 110

Complications of phimosis?

Answer 110

• Complications of circumcision: bleeding, infection, swelling
• Complications of BXO:
  
  • Phimosis
  • Meatal stenosis
  • Erosions of the glans/prepuce à can extend into urethra
  • Squamous cell carcinoma of the penis

Question 111

What is paraphimosis?

Answer 111

Paraphimosis: foreskin retracts proximal to the glans penis and becomes fixed in position

Question 112

Aetiology of paraphimosis?

Answer 112

• This is a retracted foreskin that cannot be reduced easily
• There is a ring of narrower skin
• The glans swells à if the foreskin is not reduced it may result in compromised blood supply to the glans

Question 113

Epidemiology of paraphimosis?

Answer 113

Paraphimosis usually occurs in post-pubertal boys

Question 114

Symptoms of paraphimosis?

Answer 114

• Penile pain and swelling

Question 115

Ix for paraphimosis?

Answer 115

• Clinical diagnosis

Question 116

Mx for paraphimosis?

Answer 116

• Emergency manual reduction
  
  • Needs analgesia (dorsal penile nerve block, sedation, GA)
  • If there is difficulty, apply sugar (fluid flows down concentration gradient so flows out)
• Circumcision or dorsal slit
  
  • If conservative measures fail

Question 117

Complications of paraphimosis?

Answer 117

• Penile necrosis
• Recurrence (unless circumcised)

Question 118

What is hypospadias?

Answer 118

A common birth defect where the urethra is located in an abnormal position on the ventral surface of the penis

Question 119

Aetiology of hypospadias?

Answer 119

Due to failure of development of ventral tissues of the penis, in particular the failure of ventral urethral closure

Varies in severity

• Distal is more common than proximal

Question 120

Epidemiology of hypospadias?

Answer 120

Common → 1 in 200 boys

Question 121

Signs and symptoms of hypospadias?

Answer 121

• Typically there are 3 features, but their occurrence is variable:
  
  • Ventral urethral meatus
    
    • Urethral meatus is in a variable position (80% on distal shaft or glans)
  • Ventral curvature of the shaft of the penis
    
    • More apparent on erection
  • Hooded appearance of the foreskin
    
    • Characteristic in appearance because of ventral foreskin deficiency
    • No functional significance

Question 122

Ix for hypospadias?

Answer 122

• Clinical diagnosis

Question 123

Mx for hypospadias?

Answer 123

Specialist referral

Surgery

• Not mandatory, but may be performed on functional and cosmetic grounds
• Ultimate aim is to allow boy to pass urine in a straight line while standing, and have a straight erection
• Usually done in 2-3yo (if needed)
• Boy should not be circumcised before the repair (because prepuce may be needed for the repair)

Question 124

Complications and prognosis of hypospadias?

Answer 124

Complications:

• Surgical complications:
  
  • Breakdown of the repair
  • Meatal narrowing
  • Urethral fistula, stricture, wound dehiscence (10%)

>90% surgical success rates

Question 125

What is cryptorchidism?

Answer 125

When one or both testes are not present within the scrotal sac

Aka undescended testis

Question 126

Aetiology of cryptorchidism?

Answer 126

Aetiology is unknown → may be due to hormones (e.g. oestrogen), environmental or maternal toxins, maternal alcohol consumption, genetics

Most become arrested along their normal pathway of descent

• During embryological development the testes migrate from their original retroperitoneal position near the kidneys, to their final position in the scrotum
• They descend through the inguinal canal in the 3^rd trimester
• 10% of impalpable testes have regressed in development and are absent

Testes can also be retractable

• This is when the testis can be easily manipulated into the scrotum, but the cremaster muscle pulls up the testis (seen in eliciting the cremasteric reflux by light touch on the abdo wall → pulls up testis)

Question 127

RFs for cryptorchidism?

Answer 127

• FHx,
• prematurity,
• low BW,
• maternal alcohol use,
• gestational DM

Question 128

Epidemiology of cryptorchidism?

Answer 128

Common à 5% newborn term infants, more common in premature infants

• By 3mo, only 1% are undescended

1/3 are bilateral

Question 129

Signs and symptoms of cryptorchidism?

Answer 129

• Felt on examination
  
  • Examination must be done in a warm environment with warm hands
  • Undescended testes may be palpable or impalpable
    
    • A palpable undescended testis is felt in the groin, but cannot be manipulated into the scrotum
      
      • Occasionally it can be palpated below the external inguinal ring but outside the scrotum à ectopic testis
    • If the testis is impalpable, it may be in the inguinal canal but cannot be identified, or it may be intraabdominal or absent
  • Retractable testes are easily manipulated down into the scrotum but retract back up
    
    • Parent report that the testis is sometimes obvious, esp when boy is warm and relaxed, but sometimes not

Question 130

Ix for cryptorchidism?

Answer 130

• Diagnosis usually made at routine examination of the newborn
• If there are bilateral impalpable testes à karyotype
  
  • Regarded as medical emergency
  • To exclude disorders of sex development

Question 131

Mx for cryptorchidism?

Answer 131

Surgery → orchiopexy:

• Performed around 1yo (not earlier because some spontaneously descend)
• Surgical placement of the testes in the scrotum
• Performed for the following reasons:
  
  • Cosmetic: to achieve same symmetrical appearance as other boys
    
    • If testis is absent à prothesis may be inserted when child is older
  • Reduced risk of torsion and trauma
  • Fertility: must be in scrotum, below body temp, for spermatogenesis
  • Malignancy: surgery facilitates examination but probably doesn’t reduce risk
• If testes are non-palpable:
  
  • Examination under anaesthesia + orchiopexy

Retractable testes are usually followed up annually

Some have surgery to place into scrotum

Question 132

Complications and prognosis of cryptorchidism?

Answer 132

Complications:

• Infertility
  
  • High risk if bilateral; low if unilateral
  • Reduced risk by timely orchiopexy
• Malignancy (2.2x RR with orchiopexy, 6x RR without orchiopexy)

Surgical correction is successful in 95%

Question 133

Summarise hydroceles

Answer 133

• Collection of serous fluid between the layers of the tunica vaginalis (membrane that surrounds testes along spermatic cord)
• Same underlying anatomy as a hernia, but the processus vaginalis, although patent, is not wide enough to form an inguinal hernia
• Usually asymptomatic; may appear blue; transilluminate
• You can ‘get above’ a hydrocele à differentiate from hernia
• Usually resolve spontaneously when the processus vaginalis closes in the first few months
  
  • Surgery considered if it persists beyond 2yo

Question 134

Summarise varicoceles

Answer 134

• Scrotal swelling comprising dilated (varicose) testicular veins
• Common → 15% boys; most common at puberty; more common on L side
• Usually asymptomatic but may cause a dull ache; may have blue colour; feels like bag of worms
• Conservative management if asymptomatic
  
  • Surgical ligation of gonadal veins if needed