Renal & Urology: PKD; Enuresis; HUS Flashcards
There are two types of PKD.
Which type develops in children? [1]
There are two types of polycystic kidney disease (PKD).
Autosomal recessive polycystic kidney disease (ARPKD) presents in children
Autosomal dominant, known as ADPKD, presents later in life, usually in adults.
Describe the pathophysiology of Autosomal recessive polycystic kidney disease (ARPKD) [1]
Autosomal recessive polycystic kidney disease (ARPKD):
- It is the result of a mutation in the polycystic kidney and hepatic disease 1 (PKHD1) gene on chromosome 6.
- This gene codes for the fibrocystin/polyductin protein complex (FPC), which is responsible for the creation of tubules and the maintenance of healthy epithelial tissue in the kidneys, liver and pancreas.
6The underlying pathology of ARPKD causes which consequences for patients? [3]
- Cystic enlargement of the renal collecting ducts
- Oligohydramnios, pulmonary hypoplasia and Potter syndrome
- Congenital liver fibrosis
Describe how ARPKD usually presents (and is therefore dx) [+]
ARPKD usually presents in the antenatal period with oligohydramnios and polycystic kidneys seen on antenatal scans.
Oligohydramnios is a lack of amniotic fluid caused by reduced urine production by the fetus.
- A lack of amniotic fluid leads to Potter syndrome, which is characterised by dysmorphic features such as underdeveloped ear cartilage, low set ears, a flat nasal bridge and abnormalities of the skeleton.
- The oligohydramnios leads to underdeveloped fetal lungs (pulmonary hypoplasia), resulting in respiratory failure shortly after birth.
- Additionally, large cystic kidneys can take up so much space in the abdomen it becomes hard for the neonate to breath adequately
Patients with polycystic kidney disease have a number of ongoing problems throughout life. What are they? [5]
- Liver failure due to liver fibrosis
- Portal hypertension leading to oesophageal varices
- Progressive renal failure
- Hypertension due to renal failure
- Chronic lung disease
What is the prognosis of ARPKD? [1]
Survival depends of very extensive interventions from a number of different specialties both in the neonatal period and throughout life. Around 1/3 will die in the neonatal period. Around 1/3 will survive to adulthood.
Describe what is meant by Multicystic Dysplastic Kidney? [1]
Multicystic dysplastic kidney (MCDK) is a separate condition to PKD, where one of the baby’s kidneys is made up of many cysts while the other kidney is normal.
- In rare cases it can be bilateral, which inevitably leads to death in infancy.
- MCDK is normally diagnosed on antenatal ultrasound scans.
What is meant by enuresis? [1]
What are the different classifications? [2]
The term enuresis is used to describe involuntary urination.
- Bed wetting is called nocturnal enuresis
- . Inability to control bladder function during the day is called diurnal enuresis.
- Most children get control of daytime urination by [] years and nighttime urination by []-[] years.
- Most children get control of daytime urination by 2 years and nighttime urination by 3 – 4 years.
What is meant by primary noctunal enuresis? [1]
What is the most common cause of primary nocturnal enuresis?
Primary nocturnal enuresis is where the child has never managed to be consistently dry at night.
The most common cause of primary nocturnal enuresis is a variation on normal development, particularly if the child is younger than 5 years. Often patients will have a family history of delayed dry nights.
- In this situation reassurance is important, and there is no need to jump to further investigations or management.
What are other causes of primary nocturnal enuresis (apart from variation on normal) [+]
Overactive bladder
- Frequent small volume urination prevents the development of bladder capacity.
Fluid intake prior to bedtime
- particularly fizzy drinks, juice and caffeine, which can have a diuretic effect
Failure to wake
- due to particularly deep sleep and underdeveloped bladder signals
Psychological distress
- for example low self esteem, too much pressure or stress at home or school
Secondary causes such as chronic constipation, urinary tract infection, learning disability or cerebral palsy
Describe the management of enuresis [+]
The initial step in management of primary nocturnal enuresis is to establish the underlying cause. It can be helpful to keep a 2 week diary of toileting, fluid intake and bedwetting episodes.
- This helps establish any patterns and identifies areas that may be changed, such as fluid intake before bed. It is important to take a history and examination to exclude underlying physical or psychological causes.
Reassure parents of children under 5 years that it is likely to resolve without any treatment
Lifestyle changes: reduced fluid intake in the evenings, pass urine before bed and ensure easy access to a toilet
Encouragement and positive reinforcement. Avoid blame or shame. Punishment should very much be avoided.
Treat any underlying causes or exacerbating factors, such as constipation
Enuresis alarms
- generally first-line for children
- a device that makes a noise at the first sign of bed wetting, waking the child and stopping them from urinating. It requires quite a high level of training and commitment and needs to be used consistently for a prolonged period (i.e. at least 3 months). Some families may find them very helpful, whereas others may find they add to the burden and frustration and are counter productive.
Pharmacological treatment
- Desmopressin is an analogue of vasopressin (also known as anti-diuretic hormone). It reduces the volume of urine produced by the kidneys. It is taken at bedtime with the intention of reducing nocturnal enuresis.
- Oxybutinin is an anticholinergic medication that reduces the contractility of the bladder. It can be helpful where there is an overactive bladder causing urge incontinence.
- Imipramine is a tricyclic antidepressant. It is not clear how it works, but it may relax the bladder and lighten sleep.
Define secondary nocturnal enuresis? [1]
Secondary nocturnal enuresis is where a child begins wetting the bed when they have previously been dry for at least 6 months. This is more indicative of an underlying illness than primary enuresis.
Causes of secondary nocturnal enuresis include: [5]
Urinary tract infection
Constipation
Type 1 diabetes
New psychosocial problems (e.g. stress in family or school life)
Maltreatment
Always think about abuse and safeguarding, particularly with deliberate bedwetting, punishment for bedwetting (despite parental education) or unexplained secondary nocturnal enuresis.
Management of secondary nocturnal enuresis is based on treating the underlying cause. The most common and easily treatable secondary causes are urinary tract infections and constipation. Other problems may require referral to secondary care for further management.
Diurnal enuresis is daytime incontinence. This occurs when the person has become dry at night but still has episodes of urinary incontinence during the day. This occurs more frequently in girls. Incontinence comes in two main types [2]
Urge incontinence is an overactive bladder that gives little warning before emptying
Stress incontinence describes leakage of urine during physical exertion, coughing or laughing.
Other causes of diurnal enuresis include [3]
Recurrent urinary tract infections
Psychosocial problems
Constipation
Which drugs are used for enuresis? [3]
Pharmacological treatment
- Desmopressin is an analogue of vasopressin (also known as anti-diuretic hormone). It reduces the volume of urine produced by the kidneys. It is taken at bedtime with the intention of reducing nocturnal enuresis.
- Oxybutinin is an anticholinergic medication that reduces the contractility of the bladder. It can be helpful where there is an overactive bladder causing urge incontinence.
- Imipramine is a tricyclic antidepressant. It is not clear how it works, but it may relax the bladder and lighten sleep.
Describe the pathophysiology of HUS [3]
Thrombosis of the small blood vessels throughout body due to Shiga toxin
Classically produced by E. Coli. But also:
* pneumococcal infection
* HIV
* rare: systemic lupus erythematosus, drugs, cancer
What is the classic triad of HUS? [3]
Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:
* acute kidney injury
* microangiopathic haemolytic anaemia
* thrombocytopenian- low platelets
Which medications increase the risk of HUS? [5]
Loperamide
β-lactams, trimethoprim-sulfamethoxazole, metronidazole, azithromycin
Describe the presentation of HUS
Diarrhoea is the first symptom, which turns bloody within 3 days. Around a week after the onset of diarrhoea, the features of HUS develop:
* Fever
* Abdominal pain
* Lethargy
* Pallor
* Reduced urine output (oliguria)
* Haematuria
* Hypertension
* Bruising
* Jaundice (due to haemolysis)
* Confusion
Investigations for HUS? [3]
full blood count:
- anaemia, thrombocytopaenia, fragmented blood film
U&E:
- acute kidney injury
stool culture
What is the treatment for HUS ? [3]
treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
- there is NO role for antibiotics, despite the preceding diarrhoeal illness in many patients
- Treatement for hypertension may also be needed
the indications for plasma exchange in HUS are complicated
- As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
eculizumab (a C5 inhibitor monoclonal antibody) has evidence of greater efficiency than plasma exchange alone in the treatment of adult atypical HUS
The two most common causes of nephritis in children are [2]
The two most common causes of nephritis in children are post-streptococcal glomerulonephritis and IgA nephropathy (Berger’s disease).
Describe Post-Streptococcal Glomerulonephritis [2]
Post-streptococcal glomerulonephritis occurs 1 – 3 weeks after a β-haemolytic streptococcus infection, such as tonsillitis caused by Streptococcus pyogenes.
- Immune complexes made up of streptococcal antigens, antibodies and complement proteins get stuck in the glomeruli of the kidney and cause inflammation
- Subepithelial ‘humps’ of deposits trigger inflammation, leading to epithelial cell damage, which allows the protein to filter more freely into the urine. The number of these deposits correlates with the degree of proteinuria.
- Causes AKI
NB: The clinical course of PSGN correlates to the rate of clearance of these immune complex deposits from the glomerulus.
TOMTIP. When should you consider a
Consider a diagnosis of post-streptococcal glomerulonephritis where there is evidence of recent tonsillitis caused by streptococcus. This could be a history of tonsillitis, positive throat swab results and anti-streptolysin antibody titres found on a blood test.
Describe the clinical presentation of PSGN [5]
The most commonly recognised clinical presentation among those diagnosed with PSGN is an acute nephritic syndrome;
Generalised oedema [66% of patients who present]
* Caused by water and salt retention due to renal insufficiency.
* This can progress to severe complications of fluid overload, eg. Respiratory distress due to pulmonary oedema.
Hypertension [60% of patients who present]
* Caused by water and salt retention due to renal insufficiency.
* The extent of hypertension can vary from mild to severe needing treatment
Gross haematuria[40% of patients who present];
* Red blood cell components leak from glomerular capillaries through the damaged glomerular membrane into the urine.
* Urine looks tea or cola-coloured.
Oliguria
* this varies significantly between affected individuals but also during the clinical course, as renal function initially declines and then improves.
NB: PSGN can be asymptomatic(unknown proportion), diagnosed incidentally with microscopic haematuria. Some experts speculate the incidence of PSGN is a lot higher than previously thought, but because asymptomatic cases do not present and are therefore not recognised.
Describe the investigations for post-streptococcal glomerulonephritis [+]
Urinalysis (A fresh sample should be sent to the lab to confirm haematuria and quantify the degree of proteinuria)
* Haematuria - with characteristic dysmorphic red blood cells (RBC) with or without RBC casts.
* Proteinuria - usually mild, although varying degrees of proteinuria may be found [it can reach nephrotic range in 5% of cases].
Renal function:
- decline of eGFR and elevated creatinine
Culture
* A throat or skin swab for culture should be taken to help confirm the presence of GAS.
* Only positive in 25% of cases because of the delay from initial GAS infection to the clinical presentation of PSGN (usually 1-3 weeks depending on the site of infection).
Serology:
- Anti-streptolysin (ASO)
Complement
- Low C3 levels (90% of cases) found during the initial 2 weeks, should return to baseline within 4-8 weeks.
Renal biopsy
- can provide a definitive diagnosis, but due to the self-limiting clinical course of PSGN, a biopsy is rarely needed.
Mx of PSGN? [1]
There is no specific cure for PSGN, so the focus of management is to prevent and manage any complications that arise from fluid overload
Monitoring blood pressure
- Loop diuretics provide rapid diuresis, reducing blood pressure.
- If severe hypertensive encephalopathy develops, treatment with anti-hypertensives may be needed. However, ACE-inhibitors should be used with caution due to the risk of hyperkalemia.
Monitoring renal function
- Rarely, PSGN leads to significant renal insufficiency. In some cases, dialysis may be necessary.
Antibiotic therapy should be given if there is any evidence of a persistent streptococcal infection. Early antibiotics reduce the incidence and severity of PSGN.
What are short term [3] and long term [3] complicationsof PSGN?
Short-term complications:
Pulmonary oedema
- this can manifest with respiratory distress and usually correlates to clinically evident oedema and signs of fluid overload.
Hypertensive encephalopathy
- infrequently, severe hypertension develops into hypertensive encephalopathy, requiring anti-hypertensives to reduce blood pressure
.
Severe acute kidney injury (AKI)
- requiring dialysis.
Most cases in children resolve with no long-lasting effects. There is a small subset of cases that develop late complications;
* Hypertension
* Proteinuria
* Renal insufficiency, which progresses to renal failure.
Lecture
What investigations should you conduct for enuresis? [4]
Urinary stick test culture and glucose
Early morning Urine osmolality
* To exclude diabetes insipidus
* if > 300 able to concentrate urine therefore not DI
Renal USS
Anatomy and bladder emptying
