Nephrology Flashcards
How much blood does the nephron receive?
25% of cardiac output per minute
How does GFR between neonates and children?
- 20-30ml/minute in neonates
- 90-120ml/minute by age 2 (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
- GBM
- Podocytes
- Mesangial cells
What are the features of the endothelial cells of the glomerular filtration barrier?
- Fenestrated
- Vulnerable to immune mediated injury
What are the features of the glomerular basement membrane of the glomerular filtration barrier?
- 2 proteins - Type IV collagen (COL4) and laminin
- Synthesis from podocytes and endothelial cells
- Mesangial cells playing a role in turnover
What are the features of the podocytes in the glomerular filtration barrier?
Contain proteins
-Podocin and nephrin
What are the features of the mesangial cells in the glomerular filtration barrier?
- Glomerular structural support
- Embedded in GBM
- Regulates blood flow of the glomerular capillaries
How patients with a glomerulopathy usually present?
Blood and/or protein in the urine
What does blood/protein in the urine in varying amounts dictate?
- Clinical presentation
- Suggests diagnosisq
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 can cause acquired glomerulopathy by affecting the epithelial (podocyte) cells?
- Minimal change disease
- FSGD
- Lupus
What can cause acquired glomerulopathy by affecting the basement membrane?
- Membranous glomerulopathy
- Membranoprolifertive glomerulonephritis
- Post-infection glomerulonephritis
What can cause acquired glomerulopathy by affecting the endothelial cells?
- Post-infectious glomerulonephritis
- Haemolytic uraemic syndrome
- Membranoproliferative glomerulonephritis
- Lupus
What can cause acquired glomerulopathy by affecting the mesangial cells?
- HSP
- IgA nephropathy
- Lupus
What can cause congenital glomerulaopathy by affecting the podocyte cytoskeletal integrity?
Proteins
- Podocin (autosomal recessive)
- Nephrin (autosomal recessive
What can cause congenital glomerulopathy by affecting the basement membrane proteins?
- Alport syndrome (X-linked)
- Thin basement membrane disease (autosomal dominant)
What can cause congenital glomerulaopthy by affected the endothelial/ microvascular integrity?
Complement regulatory proteins (MPGN)
What is the definition of nephrotic syndrome?
-Nephrotic range proteinuria with hypoalbuminaemia and 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 ration (early morning, PR:CR >25mg/mmol= nephrotic range)
- 24 hour urine collection (>1g/m^2/24 hours= nephrotic range
How is nephrotic syndrome diagnosed?
Oedema and proteinuria
Urine dipstix
- Protein 3+
- Blood 2+ (not frank)
Protein creatinine ration: 1200mg/mmol
Urine Na 10
Bloods
- Albumin low
- Normal creatinine
What are the atypical features of minimal change disease?
- Suggestions of autoimmune disease
- Abnormal renal function
- Steroid resistance
What type of nephrotic syndrome is most common in children?
Minimal change disease
What are the typical features of minimal change disease?
- Age (2-5yrs)
- Normal blood pressure
- Resolving microscopic haematuria
- Normal renal function
When should renal biopsy be considered in minimal changed disease?
Only if atypical features present
What is the treatment for nephrotic syndrome?
- If typical features 8 week course of prednisolone
- Second line immunosupression
What are the possible side effects of high dose glucocorticoids?
- Behavioural changes
- Increased susceptibility to infection so review varicella status and give pneumococcal vaccination
- Growth disturbance
- Hypertension
- GI distress due to increased acid
What is the spectrum of idiopathic nephrotic syndrome in childhood?
- Non-relapsing
- Infrequently relapsing
- Frequently relapsing
- Steroid dependent
- Steroid resistant
What is the pathogenesis of minimal change disease?
- Interaction between lymphocytes (T and B cells) and podocytes
- Affect the integrity of the podocytes leading to loss of size and charge barrier
What are the possible outcomes of minimal change disease?
- 95% in remission within 2-4 weeks
- 80% relapse
- 80% reach long term remission
What are the causes of acquired steroid resistant nephrotic syndrome?
Focal segmental glomerulosclerosis
- Podocyte loss
- Progressive inflammation and slcerosis
What are the congenital causes of steroid resistant nephrotic syndrome?
- NPHS1 – nephrin
- NPHS 2 – podocin
- Podocyte loss
Give examples of idiopathic nephrotic syndrome.
- Minimal change
- Focal segmental glomerularsclerosis
- Membranproliferative glomerulonephritis
Give examples of acquired nephrotic syndrome.
- HSP/IgA
- Lupus
- Post infectios
What is the approach to haematuria?
Macroscopic
-Investigated
Microscopic
- Investigated if trace on more than 2 occasions
- Haemoglobulinaria is dipstix positive and microscopy negative
Persistent haematuria and proteinuria
-Glomerular disease
What can cause haematuria?
Glomerulonephritis
- Post-infectious
- IgA/HSP
- UTI (dysuria)
- Trauma
- Stones (pain)
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 age group is usually affected by post-infectious GN?
Usually 2-5 years
What is usually the cause of post-infectious GN?
- Group a B-haemolytic streptococcus
- From throat 7-10 days
- From skin 2-4 weeks
What is the pathogenesis of post-infectious GN?
- Nephrogenic antigens on strep
- Bind to specific sites in the glomerulus or antibodies bin Ag forming circulating complexes and deposits in the kidneys
- Set up humeral and cellular response and activates alternative complement pathway
- AKI
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?
Antibiotic 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
What is the pathogenesis of IgA nephropathy?
- Increased circulating levels of GD-IgA
- Production of anti IgA1 antibodies (IgA or IgG)
- Immune complexes form in the circulation and in situ-Immune complexes in the mesangium cause local immune activation and injury
How is IgA nephropathy diagnsosed?
Clinical picture
-Negative autoimmune workup
Normal compliment
Confirmation biopsy
How is IgA nephropathy treated?
Mild disease
-Proteinuria with ACEI
Moderate to sever disease
-Immunosuppression (KDIGO)
What is the outcome of IgA nephropathy?
- Variable
- 25% in ESRF by 10 years
- Outcome better in children
What is the age of onset for HNS?
5-15 years old
How is a clinical diagnosis of HNS made?
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
How is IgA vasculitis triggered?
Occurs 1-3 days post trigger
- Viral URTI in 70%
- Strep, drugs
What is the duration of symptoms in IgA vasculitis?
- 4-6 weeks
- 1/3rd then relapse
What is the treatment for IgA vasculitis?
- Symptomatic treatment for joints and gut
- Glucocorticoid therapy (May help GI involvement but not useful in renal disease)
- Immunosuppression (trial in mod-sever disease)
- 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
