Kidneys and Urinary Tract Disorders Flashcards
Define acute glomerulonephritis
Acute inflammation of the kidneys
What is the pathophysiology of acute glomerulonephritis?
o Increased glomerular cellularity (proliferative disease) restricts glomerular blood flow →GFR is decreased
o This leads to
▪ Decreased urine output and volume overload
▪ Hypertension (may cause seizures)
▪ Oedema (usually initially periorbital)
▪ Haematuria and proteinuria
What are the causes of acute nephritis in children?
PAVI
o Post-infectious (including streptococcus)
o Vasculitis
▪ Henoch-Scholein purpura
▪ SLE
▪ Wegener granulomatosis
▪ Microscopic polyarteritis
▪ Polyarteritis nodosa
o IgA nephropathy and mesangiocapillary glomerulonephritis
o Anti-glomerular basement membrane disease (Goodpasture syndrome)
Define rapidly progressive glomerulonephritis.
Rarely you may get rapid deterioration of renal function
o This can occur with any cause of acute nephritis
o If untreated, this could lead to CKD
What are the signs and symptoms of glomerulonephritis?
- presence of risk factors
- haematuria
- oedema
- hypertension
- oliguria
- anorexia
- nausea
- malaise
- group A beta-haemolytic Streptococcus
- respiratory infections
- gastrointestinal infections
- hepatitis B
What are the investigations for glomerulonephritis?
- urinalysis and urine microscopy
- comprehensive metabolic profile
- glomerular filtration rate (GFR)
- full blood count
- erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
- complement levels
- rheumatoid factor
- anti-neutrophil cytoplasmic antibody
How do you manage acute glomerulonephritis?
-
Mild:
- Treat the underlying cause
- Supportive tx with close monitoring
- May need abx, if post-strep GN
- Phenoxymethylpenicillin
-
Moderate:
- ACE inhibitor or ARB
- May need abx, if post-strep GN
- Phenoxymethylpenicillin
- Furosemide
-
Severe:
- Corticosteroids + immunosuppressants (e.g. Rituximab)
-
With nephrotic syndrome:
- Prednisolone +/- immunosupressant
- Prophylactic Trimethoprim - for early phases of tx due to immunosuppression
How do you manage Rapidly progressive glomerulonephritis?
-
Manage existing CV RFs:
- Lifestyle
- Blood
- BP control
- Aspirin
-
For Anti-GBM
- Plasmapheresis + prednisolone + cyclophosphamide
- Prophylactic Trimethoprim: for early phases of treatment due to immunosuppression
-
For immune complex - not SLE:
- Prednisolone
- Phenoxymethylpenicillin
-
For immune complex - SLE:
- Cyclophosphamide +/- prednisolone
- Prophylactic Trimethoprim: for early phases of treatment due to immunosuppression
-
For Pauci-immune:
- Methylprednisolone + cyclophosphamide
- Prophylactic Trimethoprim: for early phases of treatment due to immunosuppression
Define post-streptococcal and post-infectious nephritis.
• Usually follows streptococcal sore throat or skin infection
o Characteristically occurs 4-6 weeks following group A beta-haemolytic streptococcus (GAS) infection (skin or throat) (Strep pyogenes)
What is the pathophysiology of post-streptococcal/post-infectious nephritis?
• Thought to be due to deposition of immune complexes in glomeruli
o Type III hypersensitivity reaction→immune complex deposition (IgG, IgM) in glomerular membrane→leads to inflammatory reaction in glomerulus
o Involves C3 complement activation and depletion
Note: to differentiate between this and IgA nephropathy – think how long after pharyngitis, they have had symptoms of glomerulonephritis
Common in developing countries
What are the clinical features of post-streptococcal/post-infectious nephritis?
- Coca-cola coloured urine (Dark)
- Peripheral oedema
What are the ix for post-streptococcal/post-infectious GN?
o Evidenceofrecentstreptococcalinfection
▪ Culture of the organism
▪ Anti-streptolysin O titre
• Detects most strains of group A streptococcus
▪ Anti-DNAse B titres
• Also detects group A beta-haemolytic streptococci
o Low complement (C3) levels
▪ Return to normal after 3-4 weeks
What is the mx of post-streptococcal/post-infectious GN?
Same as acute nephritis.
Define IgA nephropathy.
Defined by the presence of mesangial IgA immune deposits, often accompanied by C3 and IgG. Also known as Berger’s disease.
Common
Involves type III hypersensitivity reaction (IgA-IgG complex)
Usually occurs 5-7 days following an upper RTI (pharyngitis) or GI infection
Prognosis in children better than in adults
What are the clinical features of IgA nephropathy?
• Presents with MACROSCOPIC HAEMATURIA (urine appears red) in association with upper respiratory tract infection
What are the ix for IgA nephropathy?
Urinalysis: RBCs, protein
C3 and C4 complement levels: normal
Renal biopsy: diffuse mesangial IgA deposition (same as HSP)
What is the Mx of IgA nephropathy?
Same as HSP.
Most cases will resolve spontaneously within 4 weeks
Admit if inability to maintain adequate hydration with oral intake, severe abdominal pain, severe renal involvement etc
o If dehydrated→IV fluids
o If significant anaemia→may need RBC transfusion
Joint pain can be managed using paracetamol or ibuprofen
If there is scrotal involvement or severe oedema or severe abdominal pain, oral prednisolone may be given - also rest, hydration, and elevation of affected area
IV corticosteroids are recommended in patients with nephrotic-range proteinuria and those with declining renal function
In rapidly progressive nephritis: IV corticosteroid + oral prednisolone + cylophosphamine - renal transplant and dialysis may be considered.
Renal transplant may be considered in end-stage renal disease
Follow up for BP and renal function
Define Familial Nephritis.
Alport syndrome is the MOST COMMON familial nephritis
X-linked recessive disorder
Leads to progressive end-stage chronic kidney disease in early adult life
Associated with sensorineural deafness and ocular defects
Thin basement membrane disease is a differential
Define AKI.
Acute kidney injury (AKI) is a sudden, potentially reversible, reduction in renal function. Oliguria (<0.5 ml/kg per hour) is usually present.
How are AKIs stratified in terms of level of severity?
It is stratified into levels of severity by the pRIFLE and KDIGO criteria, two of the most widely used diagnostic criteria for AKI. pRIFLE uses changes in estimated creatinine clearance (eCCl), KDIGO uses serum creatinine (SCr) and changes in urine output.
What are the causes of AKIs?
The cause(s) of acute kidney injury may be:
prerenal: the most common cause in children
renal: there is salt and water retention; blood, protein, and casts are often present in the urine; and there may be symptoms specific to an accompanying disease (e.g. haemolytic uraemic syndrome [HUS])
postrenal: from urinary obstruction.
What are the pre-renal causes of AKIs?
- Hypovolaemia:
- gastroenteritis
- burns
- sepsis
- haemorrhage
- nephrotic syndrome
- Circulatory failure
- Heart failure
This is suggested by hypovolaemia. The fractional excretion of sodium is very low as the body tries to retain volume.
What are the renal causes of AKIs?
- Vascular:
- haemolytic uraemic syndrome
- vasculitis
- embolus
- renal vein thrombosis
- Tubular:
- acute tubular necrosis
- ischaemic
- toxic
- obstructive
- Glomerular
- Glomerulonephritis
- Interstitial
- Interstitial nephritis
- Pyelonephritis
If there is circulatory overload, restriction of fluid intake and challenge with a diuretic may increase urine output sufficiently to allow gradual correction of sodium and water balance. A high-calorie, normal protein diet will decrease catabolism, uraemia, and hyperkalaemia
What are the post-renal causes of AKI?
Obstruction:
congenital, e.g. posterior urethral valves
acquired, e.g. blocked urinary catheter, renal and ureteric stones
When is acute-on-chronic renal failure suggested?
Acute-on-chronic renal failure is suggested by the child having faltering growth, anaemia, and disordered bone mineralization (renal osteodystrophy).
What are the clinical features of AKI?
Non-specific symptoms such as sepsis, hypotension, decreased urine output, lower urinary tract symptoms or oedema
Acute-on-chronic renal failure is suggested by:
o Growth failure
o Anaemia
o Disordered bone mineralisation (renal osteodystrophy)
What are the investigations for AKI?
Serum creatinine
Urine output
GFR
KDIGO criteria or pRIFLE
What are the investigations for AKI?
Serum creatinine
Urine output
GFR
KDIGO criteria or pRIFLE
What is the management of an AKI?
- Use STOP AKI
- Sepsis - perform a septic screen
- Toxins - identify and stop nephrotoxic drugs (e.g. NSAIDS, amino glycoside. iodine based contrast agents)
-
Optimise volume status and BP
- Hypovolaemic - give bolus saline
- Withhold diuretics
-
Prevent harm
- Treat reversible causes e.g. urinary tract obstruction
- Treat life threatening complications e.g. acidosis and hyperkalaemia
Pre-renal failure
o Due to hypovolaemia, decreased sodium excretion because the body is trying to retain it
o Hypovolaemia should be urgently addressed with fluid replacement and circulatory support
o Dopamine/adrenaline in severe hypotension
o Furosemide if volume overloaded
What is the prognosis of AKI?
AKI in childhood generally has a good prognosis unless it is complicating a more serious condition (e.g. severe infection, following cardiac surgery)
How do you manage metabolic abnormalities in a renal-AKI?
How common are UTIs?
Affects 3-7% of girls and 1-2% of boys before age of 6 years
o More common in boys until 3 months of age (dye to congenital abnormalities) and then much more common in girls
12-30% of them have recurrence within a year
What systems are involved in UTIs?
May involve kidneys (pyelonephritis) - fever and systemic involvement
or cystitis - no fever
Why are UTIs important in childhood?
Up to half of those affected have a structural abnormality of the urinary tract
Pyelonephritis
o Involves kidneys
o Associated with fever and systemic involvement
o May damage the growing kidney and form a scar, predisposing to hypertension and progressive CKD if scarring is bilateral
What are the causative organisms of UTIs?
o Escherichia coli–most common (80%)
o Klebsiella
o Proteus
▪ More common in boys
▪ Predisposes to formation of phosphate stones (as it alkalises urine)
o Pseudomonas
▪ Suggests that there may be some structural abnormality in urinary tract
▪ More common in children with plastic catheters or ureteric stents
o Enterococcus faecalis
What are the RFs of getting a UTI?
o Antenatally diagnosed renal or urinary tract abnormality
o Incomplete bladder emptying due to infrequent voiding, vulvitis, hurried micturition, obstruction by a loaded rectum via constipation, neuropathic bladder
o Vesicoureteric reflux (found in 35% of children presenting with UTI)
o Poor hygiene e.g. not wiping from front to back in girls
What are the clinical features of UTIs in infants?
Infants: non-specific symptoms
o Fever
o Vomiting
o Lethargy/irritability
o Poor feeding/faltering growth
o Jaundice
o Septicaemia
o Offensiveurine
o Febrile seizure (> 6 months)
What are the clinical features of UTIs in children?
o Dysuria, frequency, urgency
o Abdominal pain or loin tenderness
o Fever+/-rigors
o Lethargy and anorexia
o Vomiting, diarrhoea
o Haematuria
o Offensive/cloudy urine
o Febrile seizure
o Recurrence of enuresis
What are the immediate investigations used for a UTI?
• Test urine sample in any infant/child presenting with
o Unexplained fever > 38 degrees
o An alternative site of infection who remain unwell despite treatment o Symptoms and signs suggestive of UTI
o Collection of urine samples
▪ Children in nappies
BEST METHOD: a ‘clean-catch’ sample into a waiting clean pot when nappy is removed
If not possible, use urine collection pad
Adhesive plastic bag applied to perineum after careful washing (possible contamination)
Urethral catheter if urgent, and no urine is passed
Suprapubic aspiration (fine needle attached to syringe inserted directly into a bladder under US guidance) if severely ill and non-invasive methods not possible
▪ Older children
• MIDSTREAM SAMPLE, with careful cleaning and collection to avoid contamination
o Send sample for microscopy and culture
▪ A bacterial culture of > 105 colony-forming units (CFU) of a single organism per millilitre in a properly collected specimen gives a 90% probability of infection
▪ If mixed growth of organisms→suggests contamination
Urine dipstick
o Can be used as screening test
o Culture should still be performed unless both leucocyte esterase and nitrite are negative, or is clinical symptoms and dipstick tests do not correlate
o Assess risk of serious illness (ABCDE)
▪ Temperature
▪ Respiratory rate
▪ Heart rate
▪ Do not delay treatment in a child with high risk of serious illness if urine sample cannot be obtained
▪ Capillary refill time
▪ Check for signs of dehydration
What further investigations would you do for a UTI?
The extent of further investigation beyond urine sample is controversial as they can be invasive
o There has been a move away from extensive investigation of all children with UTIs to those with atypical or recurrent UTIs
o Atypical UTIs include
▪ Seriously ill or septicaemia
▪ Poor urine flow
▪ Abdominal or bladder mass
▪ Raised creatinine
▪ Failure to respond to suitable antibiotics within 48 hours
▪ Infection with atypical organisms
o An initial ultrasound will identify serious structural abnormalities and urinary obstruction and renal defects
o If urethral obstruction is suspected, MCUG should be performed promptly
o NOTE: functional scans should be deferred for 3 months after a UTI, unless the ultrasound is suggestive of obstruction, to avoid missing a new scar and because false-positive results may be produced due to transient inflammation o NICE guidelines on further investigations:
▪ Infants and children with atypical UTI should have an ultrasound of the urinary tract to identify structural abnormalities
▪ DMSA and MCUG may also be performed in children < 6 months presenting with atypical or recurrent UTI
DMSA to check for renal scars 3 months after UTI
MCUG or MAG3 to detect obstruction and VUR
How do you interpret a urine dipstick and how does this change your management (in <3 yrs and ≥3yr old)?
If both leucocyte esterase + nitrite positive: treat as UTI (+ send urine for culture if < 3 years, suspicion of pyelonephritis, no response to treatment etc)
If both leucocyte esterase + nitrite negative: UTI unlikely, consider DDx
If leucocyte esterase positive + nitrite negative:
o Send urine sample for microscopy and culture
o If < 3 years: start antibiotic treatment
o If > 3 years: only start abx if good clinical evidence of UTI
• If leucocyte esterase negative + nitrite positive: treat as UTI
o Start abx if dipstick was with a fresh urine sample
o Send urine for culture to confirm
Summarise the investigations and management of UTIs (taking into account age)
What abx and for how long do we use for UTIs (special consideration for age)
Define enuresis.
Definition: normal micturition occurring at an inappropriate or socially unacceptable time or place, occurring after a developmental age when bladder control should be established (~5 years)
At what age do we expect children to be dry by:
- Day and night
- By day only
- Day and night: 5 yr
- Day only: 4 yrs
Define primary nocturnal enuresis.
nocturnal enuresis in which the child has never had a period of dryness longer than 6 months
Define secondary nocturnal enuresis.
nocturnal enuresis recurring after a period of more than 6 months of the child being dry at night
Define daytime enuresis.
Lack of bladder control during the day in a child old enough to be continent ( over the age of 3-5 yrs)
How common is nocturnal enuresis? Which gender is it more common in?
Nocturnal enuresis > 2 nights/week is present in 6% of 5 yr olds
1.5% of 10yr olds.
M>F by 2:1
What is the achievement of night-time dryness is dependent upon?
Dependent on the development of 2 functions:
- Ability of bladder to increase in functional capacity, aided by the action of ADH to decrease nocturnal urine production.
- The arousal of the individual to the stimulus provided by a full bladder.
What are the risk factors for nocturnal enuresis?
- Genetically determined delay in acquiring night time dryness, with ⅔ have affected first degree relative
- Young children also need reasonable freedom from stress and a measure of potential approval to lear night time continence
- Emotional stress can interfere and cause secondary nocturnal enuresis
- Most children with nocturnal enuresis are psychologically normal and tx relies on symptomatic approach
What are the causes of diurnal enuresis?
- UTI
- Constipation with faecal impaction severe enough to lower bladder volume and cause bladder neck dysplasia
- Polyuria with osmotic diuretics e.g. DM or renal concentrating disorders CKD
- Overactive bladder
- Structural abnormalities e.g. ectopic ureter or near abnormalities
What investigation do we do for nocturnal enuresis?
• Investigations for secondary NE
o Urine dipstick to check for infection, glycosuria and proteinuria
o Assessment of urine concentrating ability by measuring osmolality of an early morning urine sample
o Ultrasound of the renal tract
How do we manage primary nocturnal enuresis?
Explain:
- Common problem
- Beyond conscious control of child - no blame
- No punishment
- Fluid can be restricted 2 hrs before bed
o Children < 5 years
- Reassure the parents that many children aged < 5 yrs wet the bed and this usually resolves without intervention
- Ensure easy access to the toilet at night (e.g. potty near the bed)
- Encourage bladder emptying before bed
- Consider a positive reward system
- Star chart
o Children > 5years
- If bedwetting is infrequent (< 2 per week) reassure the parents and offer watch- and-see approach
- Can use a star or reward chart
- Don’t punish or make the child feel embarrassed If long-term treatment is required, offer:
1st line: enuresis alarm with positive reward system - ⅓ relapse
2nd line: desmopressin
o Note: fluid should be restricted 1 hour before desmopressin until 8 hours after
o May need to use detrusor-relaxing drugs if have nocturnally overactive bladder
If rapid or short-term control is required (e.g. school trips), offer desmopressin If bedwetting recurs following treatment, restart previously successful treatments and offer combination treatment with desmopressin and an enuresis alarm
Referral
If bedwetting has NOT responded to two courses of treatment, refer to secondary care, enuresis clinic or community paediatrician
Self-help group: Advice + assistance parents e.g. Eric, The children Bowel + Bladder Charity
How do we manage primary bedwetting with daytime symptoms?
Refer all children to secondary care or an enuresis clinic
Also:
- Exclude neuro causes
- Constipation should be treated
- Small portable alarm for lack of attention to bladder
- Anticholinergics - oxybutin - dampens down bladder contractions if other measure fail
What are the causes of daytime enuresis?
o Lack of attention to bladder sensation (manifestation of developmental or psychogenic problem)
o Detrusor instability (sudden, urgent urge to void induced by sudden bladder contractions)
o Bladder neck weakness
o Neuropathic bladder (bladder is enlarged and fails to empty properly, irregularly thick wall, associated with spina bifida and other neurological conditions)
o UTI
o Constipation
o Ectopic ureter (causes constant dribbling)
What would you expect to see on examination in a child with daytime enuresis?
- May reveal evidence of neuropathic bladder i.e. bladder distension, abnormal perineal sensation, anal tone, or abnormal leg reflexes, gait
- Sensory loss in distribution of S2,S3 and S4 dermatome
- Spinal lesion may be present
- Girls who get up to pool of urine due to ectopic ureter into vagina
What are the ix for daytime enuresis?
• Investigations
o Urine should be sent for MC&S
o Ultrasound may reveal abnormalities
o Urodynamic studies may be required
o MRI may be used to exclude a spinal defect
What are the causes of secondary onset nocturne?
• The loss of previously achieved urinary continence may be due to:
o Emotional upset (MOST COMMON)
o UTI
o Polyuria from an osmotic diuresis (e.g. diabetes mellitus, diabetes insipidus, CKD)
What are the investigation for secondary nocturnal enuresis?
Investigations
o Urine dipstick to check for infection, glycosuria and proteinuria
o Assessment of urine concentrating ability by measuring osmolality of an early morning urine sample
o Ultrasound of the renal tract
How do we manage secondary bedwetting?
o The following underlying causes can be managed in primary care
▪ UTI
▪ Constipation
o The following underlying causes are likely to need specialist referral
▪ Diabetes
▪ Recurrent UTI
▪ Psychological problems
▪ Family problems
▪ Developmental, attention or learning difficulties
▪ Known or suspected physical or neurological problems
Summarise the management of enuresis.
Summary
o Look for possible causes (e.g. constipation, diabetes)
o BED
- *Behavioral** - Advise onreduced fluid intake before bed, diet and toileting behaviour & Reward systems (e.g. star charts)
- *Enuresis** alarm
- *Desmopressin**: may be used 1st line if > 7 years or if short-term control is needed (e.g. holiday)
Define HSP.
Most common vasculitis of childhood
Affects small vessels
Involves tissue deposition of IgA-containing immune complexes within affected organs
What is HSP characterised by?
o Characteristic purpuric rash over extensor surfaces (esp buttocks and legs)
o Arthralgia
o Abdominal pain
o Periarticular oedema
o Glomerulonephritis
What is the epidemiology of HSP?
o Usually affects ages 3-10 years
o More common in boys (2:1)
o Peaks during winter months, often preceded by an upper RTI
What is the pathophysiology of HSP?
o Underlying aetiology is unknown – thought to be an immune-mediated vasculitis
o Possible theory: genetic predisposition and antigen exposure increase circulating IgA levels and disrupt IgG synthesis→ the IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs precipitating an inflammatory response and vasculitis
o Similar pathophysiology to IgA nephropathy
Describe the clinical features of HSP.
Haematuria
Surface rash on extensors (non- blanching raised palpable purpura), Scrotal Swelling
Polyarthritis, Abdo Pain
Fever
Rash
o Symmetrically distributed over the buttocks and extensor surfaces of arms and legs
o Trunk is usually spared
o Usually palpable
o First clinical feature in about 50% of cases
• Joint pain
o Particularly knees and ankles - ⅔ of pts
o Accompanied by periarticular oedema
• Colicky abdominal pain
o Can be treated with corticosteroids
o Can cause haematemesis and melaena - intussusception can occur
• Renal involvement
o Over 80% have haematuria or mild proteinuria
o Usually, a complete recovery is achieved
o Persistent haematuria or proteinuria is a risk factor for progressive CKD
RFs for CKD:
- Heavy proteinuria
- Oedema
- Hypertension
- Deteriorating renal function
o So, all children with HSP should be followed for a year
What are the investigations for HSP?
Urinalysis→RBCs, proteinuria, casts
24-hour urine collection for protein
Serum creatinine and electrolyte levels – to assess for renal failure
Serum IgA – raised
Coagulation studies – normal
Skin biopsy – IgA deposition
Renal biopsy – IgA, C3 and fibrin deposition in the mesangial region
What is the Mx of HSP?
Most cases will resolve spontaneously within 4 weeks
Admit if inability to maintain adequate hydration with oral intake, severe abdominal pain, severe renal involvement etc
o If dehydrated→IV fluids
o If significant anaemia→may need RBC transfusion
Joint pain can be managed using paracetamol or ibuprofen
If there is scrotal involvement or severe oedema or severe abdominal pain, oral prednisolone may be given - also rest, hydration, and elevation of affected area
IV corticosteroids are recommended in patients with nephrotic-range proteinuria and those with declining renal function
In rapidly progressive nephritis: IV corticosteroid + oral prednisolone + cylophosphamine - renal transplant and dialysis may be considered.
Renal transplant may be considered in end-stage renal disease
Follow up for BP and renal function
Define nephrotic syndrome.
Characterised by a triad of
o PROTEINURIA (> 50mg/kg/24 hours OR urine PC ratio > 300mg/mmol)
o HYPOALBUMINAEMIA(\<30g/L) o PERIPHERAL OEDEMA
What is the peak incidence of nephrotic syndrome?
2-5 yrs
What are the causes of nephrotic syndrome?
Cause is unknown but some cases occur secondary to systemic diseases e.g. Henoch-Scholein
purpura and other vasculitides, SLE, infections (e.g. malaria), allergens (e.g. bee sting)
80% of cases are due to MINIMAL CHANGE GLOMERULONEPHRITIS
What is the pathophysiology of nephrotic syndrome?
Pathophysiology
o Glomeruli are damaged and become more permeable, allowing plasma proteins to pass through leading to proteinuria
o Albumin is one of the proteins hence you get hypoalbuminaemia
o This causes peripheral and periorbital oedema as there is less oncotic pressure in blood vessels and fluid leaks out
What are some other features of nephrotic syndrome?
Other features
o Hyperlipidaemia
o Hypercoagulable state – due to loss of antithrombin III
o Predisposition to infection – due to loss of Ig
What are the clinical features of nephrotic syndrome?
- Periorbital oedema (particularly on waking) – usually the earliest sign
- Scrotal or vulva, leg and ankle oedema
- Ascites
- Breathlessness due to pleural effusion and abdominal distension
- Infection such as peritonitis, septic arthritis or sepsis due to loss of protective immunoglobulins in the urine
What are the investigations for nephrotic syndrome
• Urine protein (dipstick) - 24 hour urine collection can also be done
FBC and ESR - for infection and increased Hb also suggests intravascular fluid depletion
Urea, electrolytes, creatinine, albumin - Low Na+, high urea and/or high creatinine → intravascular fluid depletion
Complement levels: C3 and C4 - low C3- post infectious glomerulonephritis, if low C3 + C4 - SLE
Antistreptolysin O or anti-DNAase B titres and throat swab (for post-streptococcal glomerulonephritis)
Urine microscopy and culture
Urinary sodium concentration - Low (<10mmol/L) - intravascular fluid depletion
Hepatitis B and C screen - looking for cause
Malaria screen if travel abroad
Define minimal change disease.
Steroid-sensitive nephrotic syndrome
How common is minimal change disease? Who is it more common in?
Accounts for 90% of nephrotic syndrome in children.
More common in boys, Asian ethnicity, and associated with atopy
Tends to affect ages 1-10
Often precipitated by respiratory infections, recent vaccination or by immune stimulus (e.g. bee sting)
What is the pathophysiology of minimal change disease?
o T cells in the blood release cytokines-glomerular-permeability factor which specifically damages the foot processes of the podocytes making them flatter (effacement)
o Damaged foot processes lose their negatively charged coat→allow negatively charged molecules like albumin to go through
o Note: in minimal change disease, there is SELECTIVE proteinuria – larger proteins like immunoglobulins are not filtered through (unlike other causes of nephrotic syndrome)
What are the investigations of minimal change disease?
Investigations will show
o No macroscopic haematuria
o Normal blood pressure
o Normal complement levels
o Normal renal function
o Renal biopsy and histology
▪ Light microscopy: will be NORMAL (hence minimal change disease)
▪ Electron microscopy: effacement of podocyte foot processes/fusion of podocytes seen
▪ Immunofluorescence is negative
What is the management of minimal change disease?
What is the prognosis of minimal change disease?
- 20% - resolve directly
- 30% - infrequent relapses
- 50% - frequent relapses (steroid-dependent) - urine test at home
What are the complications of nephrotic syndrome?
• Hypovolaemia
o As the oedema forms, the intravascular compartment may become depleted o The child may complain of abdominal pain and feel faint
o The body will respond with peripheral vasoconstriction and urinary sodium retention
o Low urine sodium (< 10 mmol/L) and high haematocrit are suggestive of hypovolaemia
o TREATMENT: IV 0.9% saline
o If severe, IV 20% albumin infusion with furosemide may be needed (NOTE: this can precipitate pulmonary oedema and hypertension from fluid overload, and the diuretics could worsen the hypovolaemia)
• Thrombosis
o Hypercoagulable state results from:
▪ Urinary losses of antithrombin III
▪ Thrombocytosis (may be worsened by steroid therapy)
▪ Increased synthesis of clotting factors
▪ Increased blood viscosity from raised haematocrit
• Infection
o High risk of infection by capsulated bacteria (especially Pneumococcus) as immunoglobulins are also lost through urine
o Pneumococcal and seasonal influenza vaccination is recommended
o Chickenpox and shingles should be treated with aciclovir
• Hypercholesterolaemia
o Correlates inversely with serum albumin
o Cause is unknown
What are the causes of steroid dependent nephrotic syndrome?
- Focal segmental glomerulosclerosis
- ▪ Most common
- ▪ Familial or idiopathic
- ▪ Prognosis
- 30% progress to end-stage renal failure in 5 years
- 20% respond to cyclophosphamide, cyclosporin, tacrolimus or rituximab
- Recurrence post-transplant is common
- o Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis) ▪ More common in older children
- Haematuria
- Low complement levels
- Decline in renal function over many years
- o Membranous nephropathy
- ▪ Associated with hepatitis B
- ▪ May precede SLE
- ▪ Most remit spontaneously within 5 years
What is the management of steroid resistant nephrotic syndrome?
o Refer to paediatric nephrologist
o Management of oedema using diuretic therapy, salt restriction, ACEi and sometimes NSAIDs (which may reduce proteinuria)
o Genetic testing is available and helps direct management e.g. withdrawal of immunosuppression or supplementation of CoQ10 if CoQ10 pathway defect
Summarise congenital nephrotic syndrome.
Presents in first 3 months of life
Rare - genetic testing recommended - 70% have an underlying genetic defect
More common in Finns and in consanguineous families
Associated with high mortality due to complications of hypoalbuminaemia (intensive nutritional management better)
Management: may need unilateral nephrectomy (to manage albuminuria) and subsequent
dialysis, definitive treatment by renal transplantation
What are the causes of renal masses unilaterally?
▪ Multicystic kidney
▪ Compensatory hypertrophy
▪ Obstructed hydronephrosis
▪ Renal tumour (Wilms tumour)
▪ Renal vein thrombosis
What are the causes of renal masses biilaterally?
▪ Polycystic kidneys (autosomal dominant + autosomal recessive)
▪ Tuberous sclerosis
▪ Renal vein thrombosis
Define renal calculi.
Presence of crystalline stones (calculi) within the urinary system (kidneys and ureters)
How common are renal calculi?
UNCOMMON in childhood
What is the most common type of calculi? What is it associated with?
The MOST COMMON type of stone are phosphate stones, which are associated with infection (Proteus)
What do calcium containing stones occur with?
Calcium-containing stones may occur with idiopathic hypercalciuria, increased urinary urate and oxalate excretion
What predisposing factors are there for renal calculi?
o UTI
o Structural anomalies of the urinary tract o Metabolicabnormalities
Define nephrocalcinosis. What is it associated with? What can it be a complication of?
Nephrocalcinosis (depositions of calcium in the parenchyma) may occur in hypercalciuria, hyperoxaluria and distal renal tubular acidosis
This may be a complication of furosemide therapy in neonates
What are the clinical features of renal calculi?
Haematuria
Loin or abdominal pain
UTI
Passage of a stone
What are the investigations for renal calculi?
- Urine dipstick: for microscopic haematuria
- Non-contrast CT (gold-standard)
- U&Es and creatinine to check renal function
What is the management of renal calculi?
- Conservative management with IV fluids, analgesia (morphine) and anti-emetics (ondansetron)
- Bacterial Infection - antibiotic treatment with co-trimoxazole or nitrofurantoin, or surgical decompression
-
Small stones - medical expulsive therapy
- May pass naturally
- Tamsulosin OR Alfuzosin OR Silodosin
- Larger stones and those that do not pass spontaneously - surgical removal
- 1st line: ESWL (extracorporeal shock wave lithotripsy or ureteroscopy
- High fluid intake is recommended in all affected children
Further ix for structural abnormalities
Define Haemolytic Uraemic Syndrome
HUS is a triad of
o Microangiopathic haemolytic anaemia (MAHA): intravascular haemolysis and red cell fragmentation
o Acute renal failure
o Thrombocytopenia
What are the 2 forms of HUS?
o D+: diarrhoea-associated (prodrome of diarrhoea) ▪ More common in young children
o D-: no prodromal illness identified
What is HUS secondary to usually?
Typical HUS is secondary to GI infection with E coli O157:H7
o Acquired through contact with farm animals or eating uncooked beef
o Produces verocytotoxin that enters GI mucosa and attacks endothelial cells, where it causes intravascular thrombogenesis
Less often caused by Shigella
What is the pathophysiology of HUS?
o A toxin causes endothelial damage which leads to platelet activation
o Endothelial injury results in platelet aggregation and the release of unusually large vWF multimers and activation of platelets and clotting cascade
o There is also fibrin deposition in small vessels leading to microthrombi
o Damaged RBCs clog up vessels
▪ The glomerular afferent arteriole and capillaries are particularly vulnerable (undergo fibrosis necrosis)
▪ This leads to renal ischaemia and acute renal failure
o The thrombi also promote intravascular haemolysis
o MAHA results from damage to RBCs
What are the clinical features of HUS?
• GI prodromal illness
o Severe abdominal colic
o Watery diarrhoea that becomes bloodstained
• General
o Malaise
o Fatigue
o Nausea
o May have fever
• Renal
o Oliguria or anuria
o Haematuria
What are the investigations for HUS?
• FBC
o Normocyticanaemia
o High neutrophils
o Very low platelets
• U&Es
o High urea
o High creatinine
o High K+
o Low Na+
Clotting: normal (DIC does not usually occur)
LFTs
o High unconjugated bilirubin
o High LDH from haemolysis
Blood cultures
ABG: low pH, low bicarbonate, low PaCO2, normal anion gap
Blood film: schistocytes, high reticulocytes and spherocytes
Urinalysis
Stool samples: MC&S
What is the management of HUS?
- Consult nephrology and haematology specialists
- Children with the typical presentation should be admitted
- Supportive
- Monitor urine output and fluid balance
- In diarrhoea HUS(D+HUS) use of antibiotics can worsen disease
- Maintain adequate hydration status (avoid cardiopulmonary overload) – IV isotonic crystalloids
- Monitor blood pressure (treat If elevated)
- Treatment should be with CCBs (ACE inhibitors can reduce renal perfusion)
- If anaemic, red cell transfusion is needed
- Avoid antibiotics, anti-diarrhoeals, narcotic opioids and NSAIDs
- 50% of patients will require dialysis in the acute phase
- If irreversible renal failure has occurred then renal transplant will be needed
- Long-term follow-up is necessary because there may be persistent proteinuria and the
- development of hypertension and progressive CKD
-
Atypical HUS has no diarrhoeal prodrome, may be familial and frequently relapses
- This has a high risk of hypertension and progressive CKD with a high mortality
- Thrombotic thrombocytopenic purpura will require plasmapheresis
Define chronic kidney disease.
CKD is the progressive loss of renal function that can be caused by many conditions
How common is stage 5 kidney disease in children?
Rare
What are the causes of CKD in children?
Congenital and familial causes are more common in childhood than acquired diseases
o Commonest cause: structural malformations and hereditary nephropathies
o Renal dysplasia +/-reflux
o Obstructive uropathy
o Glomerular disease
o Congenital nephrotic syndrome
o Tubulointerstitial diseases
o Renovascular disease
o Polycystic kidney disease
o Metabolic
Describe Stage 1 to 5 CKD.
What are the clinical features of severe CKD?
• CLINICAL FEATURES (of stage 4/5 CKD):
o Anorexia and lethargy
o Polydipsia and polyuria
o Faltering growth/growth failure
o Bony deformities from renal osteodystrophy
o Hypertension
o Acute-on-chronic renal failure (precipitated by infection or dehydration)
o Incidental finding of proteinuria
o Unexplained normochromic, normocytic anaemia
Symptoms before these stages unlikely
Many children will have had their renal disease detected antenatally
What are the aims of CKD management?
The aims of management are to prevent the symptoms and metabolic abnormalities of chronic kidney disease, to allow normal growth and development, and to preserve residual renal function.
The management of these children should be conducted in a specialist paediatric nephrology centre.
What are the 1st line, 2nd line and additional treatments for CKD?
What should we do if anaemia presents in CKD?
o Erythropoietin stimulating agent can be used
o Iron supplementation should also be given
What should we do if secondary hyperparathyroidism occurs in CKD?
o Decreased activation of vitamin D leads to phosphate retention and hypocalcaemia, which, in turn, leads to secondary hyperparathyroidism and eventually osteitis fibrosa cystica and osteomalacia
o Phosphate restriction (by reducing milk), using calcium carbonate as a phosphate binder and activated vitamin D supplements can help
What should we do if metabolic acidosis occurs in CKD?
o Many children will also have obligatory loss of salt and water
o They need salt supplements and a lot of water
o Treatment with bicarbonate supplements is needed to prevent acidosis
What diet advice should we give in CKD?
o Anorexia and vomiting are common
o Calorie supplements or NG/gastrostomy feeding is often necessary to optimise growth
o Protein intake should be sufficient to maintain growth and normal albumin (but preventing the accumulation of toxic metabolic by-products)
How should we treat hormonal abnormalities in CKD?
o Growth hormone resistance, characterised by a high GH level but poor growth, is a feature of CKD
o Recombinant human GH is effective in improving growth for up to 5 years of use
o Many children with stage 4/5 CKD will have delayed puberty or subnormal pubertal growth spurt
What are the different aspects of CKD tx?
- Medical
- Diet
- Complications:
- Anaemia
- Secondary hyperparathyroidism
- Metabolic acidosis
- Salt and water loss
- Hormonal abnormalities
