Nephrology Flashcards
how much blood does the nephron receive?
25% of cardiac output per minute
how does GFR differ between neonates and children?
neonates: 20-30ml/minute
2 years old: 90-120ml/minute (same as adults)
what are the 5 functions of the kidneys?
- waste handling
- water handling
- salt balance
- acid base control
- endocrine (RBC/BP/Bone health)
what are the components of the glomerular filtration barrier?
endothelial cells: fenestrated (vulnerable to injury)
GBM (laminin and collage IV)
podocytes (podocin and nephrin)
mesangial cells
how do patients with a glomerulopathy usually present?
blood and/or protein in the urine
what does proteinuria signify?
glomerular injury
what leans towards nephritic syndrome?
- increasing haematuria
- intravascular overload
what leans towards nephrotic syndrome
- increasing proteinuria
- intravascular depletion
what are causes of acquired glomerulopathy
minimal change disease (podocyes) post infectious glomerulonephritis (endothelial cells, GBM) haemolytic uraemic syndrome (endothelial cells) HSP (mesangial cells) IgA nephropathy (mesangial cells)
what are causes of congenital glomerulaopathy
podocyte cytoskeletal integrity
basement membrane proteins
endothelial cells/microvascular integrity
what is the definition of nephrotic syndrome?
nephrotic range proteinuria
hypoalbuminaemia
oedema
why does oedema occur in nephrotic syndrome?
starling’s forces
- osmotic vs hydrostatic
- protein is a magnet to water
- leakage of protein into 3rd space leads to osmotic force
how can proteinuria be tested for?
dipstix
- 3 or above= abnormal
protein creatinine ratio
- PR:CR >250mg/mmol= nephrotic range)
24 hour urine collection
- >1g/m^2/24 hours= nephrotic range
how is nephrotic syndrome diagnosed?
oedema
proteinuria
- urine dipstix: protein 3+, blood 2+ (not frank)
- protein creatinine ratio: 1200mg/mmol
- urine Na 10mmol/l
bloods
- albumin low
- normal creatinine
what are the typical features of minimal change disease?
age: 1 - 10
blood pressure: normal
renal function: normal
frank haematuria: none
what type of nephrotic syndrome is most common in children
minimal change disease
when should renal biopsy be considered in minimal changed disease?
if atypical features present
- suggestions of autoimmune disease
- steroid resistance
- abnormal renal function
what is the treatment for nephrotic syndrome?
- typical features: 8 week course of prednisolone
- second line: immunosupression
what are the possible side effects of high dose glucocorticoids?
- behaviour change
- mood lability
- sleep disturbance
- susceptibility to infection
- growth disturbance
- hypertension
- GI distress due to increased acid
what is the pathogenesis of minimal change disease?
interaction between lymphocytes (T and B cells) and podocytes
what are the possible outcomes of minimal change disease?
95% remission within 2-4 weeks
80% relapse
80% reach long term remission
what are the causes of steroid resistant nephrotic syndrome?
acquired: focal segmental glomerulosclerosis
congenital: podocyte loss (NPHS1 – nephrin, NPHS 2 – podocin)
What is the approach to haematuria?
macroscopic/frank: investigate
microscopic: dipstick
associated proteinuria = glomerular disease
what can cause haematuria?
systemic: clotting disorders
renal: glomerulonephritis, tumours, cysts
malignancies: sarcomas
stones
UTI
trauma
urethritis
how does nephritic syndrome present?
haematuria and proteinuria
reduced GFR
- oliguria
- fluid overload (raised JVP and oedema)
- hypertension
- worsening renal failure
what type of AKI can nephritic syndrome cause?
intrarenal AKI
give examples of causes of glomerulonephritis.
- post Infectious GN
- HSP / IgA nephropathy
- membranoproliferative GN
- lupus Nephritis
- ANCA positive vasculitis
what is usually the cause of post-infectious GN?
group A beta-haemolytic streptococcus
- throat: 7 - 10 days
- skin: 2 - 4 weeks
what is the pathogenesis of post-infectious GN?
- antigen mimicry
2. Ab-Ag complexes
how is post-infectious GN diagnosed?
- bacterial culture
- positive ASOT
- low C3 normalises
what is the prognosis of post-infectious GN?
good prognosis with no recurrence
how is post-infectious GN treated?
- antibiotics for group A strep
- support renal functions
- overload / hypertension (give diuretics)
what is the most common GN worldwide?
IgA nephropathy
who does IgA nephropathy usually affect?
older children and adults
1-2 day after an URTI
how does IgA nephropathy present clinically?
recurrent macroscopic haematuria
+/- chronic microscopic haematuria
varying degree of proteinuria
how is IgA nephropathy diagnosed?
clinical picture
confirmation biopsy: mesangial IgA, IgG and C3 deposits
how is IgA nephropathy treated?
mild disease: proteinuria with ACEI
moderate - severe disease: immunosuppression (KDIGO)
what is the outcome of IgA nephropathy?
variable
- 25% in ESRF by 10 years
- outcome better in children
how is a clinical diagnosis of HNS made?
age: 5 - 15 yrs
mandatory palpable purpura plus 1 of:
- abdominal pain
- renal involvement
- arthritis or arthralgia
- biopsy (IgA deposition)
what is the most common childhood vasculitis?
IgA vasculitis
describe IgA vasculitis
most common vasculitis
very similar to IgA nephropathy
- mesangial cell injury
small vessel vasculitis - arterioles, capillaries, venules
occurs 1 - 3 days post trigger: viral URTI, strep, drugs
symptoms: 4 - 6 wks (1/3 relapse)
treatment: symptomatic, glucocorticoid therapy, immunosuppression, long term hypertension and proteinuria screening
What is AKI?
Abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes
What are the clinical features of AKI?
- Anuria/oliguria (<0.5ml/kg/hr)
- Hypertension with fluid overload
- Rapid rise in plasma creatinine
How is AKI defined?
Serum creatinine: > 1.5x age specific reference creatinine (or previous baseline if known)
Urine output<0.5 ml/kg for > 8hours
What is AKI 1?
Measured creatinine >1.5-2x reference creatinine/ULRI
What is AKI 2?
Measured creatinine 2-3x reference creatinine/ULRI
What is AKI 3?
Serum creatinine >3x reference creatinine/ULRI
How is AKI managed?
Monitor
-Urine output, PEWs, BP, weight
Maintain
-Good hydration
Minimise
-Drugs
What causes pre-renal AKI?
Perfusion problem
What are the intrinsic causes of AKI?
Glomerular disease
- HUS
- Glomerulonephritis
Tubular injury: Acute tubular necrosis (ATN)
- Consequence of hypoperfusion
- Drugs
Interstitial nephritis
-NSAID, autoimmune
What causes post-renal AKI?
Obstruction
What causes atypical HUS?
- Autoimmune process
- Can be congenital or acquired
What can cause HUS?
Typical: post-diarrhoea
-Entero-haemorrhagice E. coli (vertoxin producing E.coli or Shiga toxin
Other causes
-Pneumococcal infection, drugs
What serotype of E.coli is responsible for HUS?
E.coli O157
What is the period of risk of HUS with E coli O157 infection?
- Up to 14 days after the onset of diarrhoea
- 15% develop HUS
What is blood diarrhoea in children?
Medical emergency
What organs are vulnerable in shiga toxin dissemination?
- Kidneys
- Brain
- Lungs
- Pancreas
- Adrenals
- Heart
What is the triad of HUS?
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Acute renal failure / AKI
How is HUS managed?
Monitor (5 kidney functions)
- Fluid balance, electrolytes, acidosis
- Hypertension
- Aware of other organs
Maintain
- IV normal saline and fluid
- Renal replacement therapy
Minimise
-No antibiotics
What are the potential long term consequences of AKI?
- Blood pressure
- Proteinuria monitoring
- Evolution to CKD
What can cause paediatric CKD?
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) 55%
- Reflux nephropathy
- Dysplasia
- Obstructive Uropathy (example - posterior urethral valves)
Hereditary conditions 17%
- Cystic kidney disease
- Cystinosis (most common inherited tubular disease)
Glomerulonephritis 10%
What syndromes may be associated with CAKUT?
- Turner
- Trisomy 21
- Branchio-oto-renal
- Prune Belly syndrome
What are the stages of CKD?
- Normal: GFR 90-120
- CKD 2: GFR 60-89
- CKD 3: GFR 30-59
- CKD 4: GFR 15-29
- CKD 5: ESRD
What is presentation of CKD dependent on?
Which kidney functions are affect
How can CKD present?
Asymptomatic
Abnormalities in
- Waste handling
- Water handling
- Salt balance
- Acid base control
- Endocrine functions
Bladder dysfunction
Itch
How does NICE define UTI?
Clinical signs PLUS
- Bacteria culture from midstream urine
- Any growth on suprapubic aspiration or catheter
How do neonates present with UTI?
- Fever
- Vomiting
- Lethargy
- Irritability
- Poor feeding
- Failure to thrive
How do pre-verbal children present with UTIs?
- Fever
- Abdominal pain
- Abdominal/loin tenderness
- Vomiting
- Poor feeding
- Lethargy
- Irritability
How doe verbal children present with UTI?
- Frequency
- Dysuria
- Dysfunctional voiding
- Changes to continence
- Abdominal/loin pain or tenderness
- Fever
- Malaise
- Vomiting
How can urine samples be obtained in children?
- Normal social cleanliness - water
- Clean catch urine or midstream urine
- ?? collection pads, urine bags (contamination risks)
- Sick infants via catheter samples or suprapubic aspiration (USS)
- Acutely unwell - do not delay treatment to obtain sample
How is UTI diagnosed?
Suggestive tests
- Dipstix: Leucocyte esterase activity, nitrites but unreliable < 2 yrs of age
- Microscopy: Pyuria >10 WBC per cubic mm and bacturia
Culture > 105 Colony forming units
-E.coli
Why do we worry about UTIs?
- UTI on top of vulnerable kidney with VUR can lead to scarring
- Scarring predisposes to future problems
How is VUR graded?
Unilateral/bilateral
- Grade1: Ureter only
- Grade2: Ureter, pelvis and calyces
- Grade3: Dilatation of ureter
- Grade4: Moderate dilatation of ureter, pelvis, tortuous ureter and obliteration of fornices
- Grade5: Gross dilatation/tortuosity, no papillary impression in calyces
What are the principles of investigating the renal tract?
Screening for children at risk of progressive scaring
-Reflux nephropathy
Capture those with renal dysplasia
Urological abnormalities / unstable bladder
-Voiding dysfunction
Who should be investigated with UTI?
- Upper tract symptoms
- Younger <6 months
- Recurrent
- Septic presentation
What investigations are used in complex UTI?
Ultrasound
-Structure
DMSA (isotope scan)
-Scaring/function
Micturating cystourethrogram MAG 3 scan
-Dynamic
How are UTIs treated?
Lower tract
-3 days oral antibiotic
Upper tract / pyelonephritis
-Antibiotics for 7-10 days (Oral if systemically well_
-Prophylaxis is falling out of favour unless anatomical abnormality or high grade VUR
Prevention
How can UTIs be prevented
- Fluids, hygiene, constipation treatment
- Voiding dysfunction
What factors affect progression of CKD?
- Late referral
- Hypertension
- Proteinuria
- High intake of protein, phosphate and salt
- Bone health
- Acidosis
- Recurrent UTIs
What is proteinuria a sign of in CKD?
Renal injury and causes ongoing renal injury
What system is used to classificy CKD and prognosis?
KDIGO
How is BP measured in children?
Doppler
-Children under 5
Sphigmanomter
Oscillomerty
White coat effect use 24 hour Ambulatory Blood Pressure Monitoring
-Need to be about 120cm (5/6 years of age to tolerate)
What factors affect blood pressure?
- Sex
- Age
- Height
How is hypertension defined in a child?
95th centile or higher
What is considered borderline in terms of hypertension in children?
Between the 90th and 95th centiles
Why does bone disease occur in kidney disease?
- Kidneys excrete phosphate.
- Damage leads to high levels of phosphate and therefore high levels of PTH
- PTH aims to increase serum calcium and so drives calcium out of the bones
- Kidney unable to activate vitamin D. Activated vitamin D would normally suppress PTH
How is metabolic bone disease treated?
- Low phosphate diet
- Phosphate binders
- Active Vitamin D
If ongoing poor growth then growth hormone (if normalised bone biochemistry)
Why is there increase cardiovascular risk in kidney disease?
Accelerated atherosclerosis
- Traditional risk factors
- Anaemia and metabolic bone disease (high PTH levels)
How can cystic renal disease be defined?
Simple
Developmental
- Dysplasia
- Multicystic dysplastic
Genetic
- Autosomal Recessive (ARPKD)
- Autosomal Dominant (ADPKD)
- Syndromic (Various forms of Juvenile Familial Nephronophthisis (JFN))
Acquired
-Cancer
What is the incidence of developmental multicystic kidney?
1 in 2,000-4,000 (usually sporadic)
How does developmental multicystic kidney present?
Non-functioning kidney
Ureteric atresia
Hypertrophy of the normal contralateral kidney
What is Potter sequence?
- Decreased amniotic fluid
- Pulmonary hypoplasia
- Fetal compression of faces, contracture
- Bilateral renal agenesis (absent ureteric bud)
- AR polycystic kidney disease (truncating mutation)
How do babies with autosomal recessive polycystic kidney disease present?
- Antenatally large bright kidneys
- Oligohydramnios
- Severe respiratory distress (pulmonary hypoplasia, nephromegaly mass effect)
What are the target organs in ARPKD?
- Renal collecting duct
- Hepatic ductal plate
What are the target organs in ADPKD?
- All nephron segments
- Liver
- Pancreas
- Brain
What are the target organs in nephronophthisis?
- Tubular (medullary)cysts
- Retina
- Liver
- Brain
- Bones
What are the clinical features of ciliopathy syndromes?
- Renal cysts on US
- Retinal pigment increases
- Cystic tubular dilatation on renal biopsy
- Cerebellar vermis aplasia (molar tooth sign)
What is RCAD?
Renal cysts and diabetes
-Autosomal dominant glomerulocystic kidney disease
How does RCAD present?
- US - cortical cysts
- Early onset diabetes mellitus (MODY)
- Genetic heterogeneity (HNF1β mutations)
What is Alport syndrome?
- Glomerular Basement Membrane disease
- Collagen 4 abnormalities
- X linked dominant inheritance (COL4A5 gene on the X chromosome)
- Less common AR and AD inheritance
What is the clinical presentation of Alport syndrome?
Renal
- Haematuria - microscopic and macroscopic
- Proteinuria
- Hypertension
Deafness - high tone sensori-neural loss
Renal failure in early adult life
-Age 20-30 years
Eye changes
- Lenticonus
- Macular changes in retina
