Nephrology Flashcards
What is GFR as a neonate and when does it become similar to adults?
Neonate=20-30ml/min/1.73m2
Age 2yrs equals adult 90-120
(Kidney receives 25% of CO/min)
What are the functions of the kidney?
- Waste handling- urea and creatinine
- Water handling
- Salt balance-Na & calcium phosphate
- Acid base control-bicarb
- Endocrine-red cells/BP/bone health-erythropoietin, renin angiotensin aldosterone system, parathyroid hormone
How do those with glomerulopathy present?
Blood & protein in varying amounts dictate clinical presentation & suggests diagnosis
Injury to one part of the GFB affects the other components
What does proteinuria signify?
Signifies glomerular injury
Acquired glomerulopathy is common and what type depends on what components of GFB is affected. What are these types?
Minimal change disease=epithelial cell (podocyte)
PIGN=basement membrane
PIGN, HUS=Endothelial cell
HSP/IgA nephropathy=mesangial cell
Congenital glomerulopathy is rare and the type depends on the layer involved, what are they?
Congenital nephrotic syndrome (proteins=podocin (AR), nephrin (AR))
Alport syndrome (AL)
Thin basement membrane disease (AD)
Complement regulatory proteins (MPGN)
How much proteinuria is too much and how is this checked?
- Dipstix
Give concentration
≥ 3+ usually abnormal
False positives and negatives - Protein Creatinine Ratio (practical)
Early morning urine (best)
normal: Pr:CR ratio <20mg/mmol
Nephrotic range: >250mg/mmol
>500mg/mmol - oedema - 24hr urine collection (gold standard)
normal <60mg/m²/24hrs
Nephrotic range>1g/m²/24hrs
Adults >3.5g/24hrs
What is NephrOtic syndrome?
- Nephrotic range proteinuria
- Hypoalbuminemia
- Oedema (increasing 3rd space fluid v)
After what do children usually present with minimal change disease or steroid sensitive nephrotic syndrom?
Intercurrent illness such as gastroenteritis
What does a urine sodium <20 mean?
You are holding onto water
What are the features of MCD (nephrotic syndrome)?
- Age 1-10
- Normal BP
- No frank haematuria
- Normal renal function
Atypical features:
- Suggestions of autoimmune disease
- Abnormal renal function
- Steroid resistance (failure to go into remission after 4 weeks of high dose oral steroids)
ONLY then consider a renal biopsy
How is nephrotic syndrome treated?
If typical features=PREDNISOLONE 8 WEEKS
What can be done about the infection risk that is increased from the use of high dose glucocorticoids?
- Varicella status
- Pneumococcal vax
- Abx prophylaxis
What does steroid sensitivity predict?
Diagnosis and prognosis
90% steroid sensitive=MCD
Steroid resistance is more suggestive of focal segmental glomerulosclerosis
What is the pathogenesis of Nephrotic syndrome?
Interaction between lymphocytes (T&B) and podocytes
What is the outcome of steroid sensitive nephrotic syndrome?
Remission
95% in 2-4 weeks
Relapse
80%
80% long term remission
Frequently relapsing=
Second line immunosuppression
- Steroid toxicity
- Steroid dependant and frequent relapses (>4/year)
What are the causes of steroid resistant nephrotic syndrome?
Acquired:
Focal Segmental Glomeruloscerosis (FSGS)
- Podocyte loss
- Progressive inflammation and sclerosis
(50% of these children will
need renal replacement therapy in five years.)
Congenital:
Infant presentations
NPHS1 – nephrin
NPHS 2 – podocin
Podocyte loss
What is the investigation for microscopic haematuria?
Dipstix adequate
Investigate if >trace on 2 equations
Haemoglobinuria=stix +ve & microscopy negative
Associated proteinuria = glomerular disease
What can cause haematuria?
Systemic
- clotting disorders
Renal
- Glomerulonephritis
- Tumour
Wilm’s - nephroblastoma
- Cysts
Malignancies - sarcomas
Stones
UTI
Trauma
Urethritis
How does Nephritic syndrome present?
Clinical diagnosis describes glomerulonephritis
Haematuria and proteinuria
Reduced GFR (creatinine)
- Oliguria
- Fluid overload (Raised JVP, oedema)
- Hypertension
- Worsening renal failure = Rapidly Progressive GN
Intrarenal cause of Acute kidney injury (AKI)
What does raised creatinine indicate?
Abnormal renal function
Acquired glomerulopathy: which components can be affected and if they are what condition do they cause?
Epithelial cell (podocyte) = MCD, FSGS, Lupus
Basement Membrane = Membranous glomerulopathy, MPGN, PIGN
Endothelial cell = post infectious glomerulonephritis (PIGN), Haemolytic Uraemic Syndrome, Membranoproliferative Glomerulonephritis (MPGN), Lupus, ANCA vasculitis
Mesangial cell = HSP / IgA nephropathy, Lupus
For nephritic syndrome for example how is it investigated?
Radiology
Renal USS – normal
Chase most likely diagnosis
- ASOT - Raised 1200
- Positive throat swab group A strep
Immunology workup
- Complement C3 low, normal C4
- Autoimmune diseases (ANA, ANCA negative)
Biopsy
Not required at present
What is acute post infectious glomerulonephritis and what causes it?
Age of onset-usually 3-5years
Cause:
- Usually group A strep
- Beta haemolytic
- Site (throat 7-10 days, skin 2-4weeks)
Acute post infectious glomerulonephritis is SELF LIMITING: How is it diagnosed?
- Bacterial culture
- positive ASOT
- low C3 normalises
Remember differential diagnosis (IgA / Lupus / MPGN)
ASOT – Anti streptolysin O titre
What is the treatment of Acute post infectious glomerulonephritis?
- Abx
- Support renal functions (electrolyte/acid base)
- Overload/HT-Diuretics
NOT RECURRENT
What is the commonest glomerulonephritis and how does it present?
Most common glomerulonephritis
1-2 days after URTI
Usually older children and adults
Clinically:
Recurrent macroscopic haematuria
+/-Chronic microscopic haematuria
Varying degree of proteinuria
Clinical diagnosis
How is IgA nephropathy diagnosed?
Clinical picture - Negative autoimmune workup and normal compliment
Confirmation biopsy (IgA deposits within the mesangial cells)
What is the treatment for IgA nephropathy: mild & severe?
Mild=proteinuria with ACEI
Moderate to severe=Immunosuppression (KDIGO)
What is the age of onset of HSP IgA related vasculitis?
Age of onset=5-15 years
How is HSP IgA related vasculitis clinically diagnosed?
Mandatory palpable purpura
+ one of 4
1. Abdominal pain
2. Renal involvement
3. Arthritis or arthralgia
4. Biopsy -IgA depostition
IgA vasculitis is the most common childhood vasculitis affecting what vessels?
Small vessel vasculitis
- Overlaps with IgA nephropathy
- Non granulomatous HSP
What is IgA vasculitis triggered by and what is the duration of symptoms?
1-3 days post trigger
- Viral URTI
- Strep, drugs
4-6 weeks duration and a 1/3 relapse`
(Nephritis-mesangial cell injury)
How is IgA vasculitis treated?
Symptomatic-Joints, gut
Glucocorticoid therapy
- Not helpful in mild nephritis
- May help with gastrointestinal involvement
Immmunosuppresion - Trial in moderate to severe renal disease
Long term=Hypertension and proteinuria screening
What is AKI and what are the clinical signs of it?
“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”
Anuria/oliguria (<0.5ml/kg/hr)
Hypertension with fluid overload
Rapid rise in plasma creatinine
How is AKI diagnosed?
Serum creatinine: > 1.5x age specific reference creatinine (or previous baseline if known)
Urine output<0.5 ml/kg for > 8hours
What are the AKI warning score criteria?
AKI 1: Measured creatinine >1.5-2x reference creatinine/ULRI
AKI 2: Measured creatinine 2-3x reference creatinine/ULRI
AKI 3: Serum creatinine >3x reference creatinine/ULRI
What are the 5 key kidney functions and what is associated with them in assessment?
Waste handling
Water handling
Salt balance
Acid base control
Endocrine
red cells / blood pressure / bone health
Waste – urea / creatinine
Salt – sodium / potassium / calcium drops / phosphate rise
Acid base – bicarbonate
Endocrine – Renin aldosterone angiotensin system / PTH / activation of Vitamin D (Vit D = sterole) / Erythropoietin
How is AKI managed (think 3 Ms)?
PREVENTION
3Ms:
Monitor=PEWS(BP), Urine Output, weight
Maintain=good hydration / electrolytes / acid - base
Minimise=Drugs
What are the possible causes of AKI?
Pre-renal-Perfusion problem
Renal
Post renal-Obstructive uropathies
What are the general intrinsic renal problems that can cause AKI?
Glomerular disease
- HUS
- Glomerulonephritis
Tubular injury
- acute tubular necrosis
(ATN) (Consequence of hypoperfusion, Drugs)
Interstitial nephritis
- NSAID, autoimmune
What is the definition of haemolytic uraemic syndrome (parameters)?
HAEMOLYSIS
- Packed cell volume <30%
- Hb level <10g/dl & fragmented erythrocytes on blood film
THROMBOCYTOPENIA
Platelet count <150x10⁹/l
AKI
- Serum creatinine greater than the age-related range (>97th pc)
- GFR <80 mls/min/1.73m²
Proteinuria
What causes typical HUS to present?
Typical HUS - post diarrhoea
Entero-Haemorrhagic E.coli (EHEC)
- Verotoxin producing E.coli – VTEC or Shiga toxin (STEC)
Other causes=pneumococcal infection, drugs
What causes atypical HUS?
Defect (overactivation) in alternative compliment pathway - autoimmune, drugs, hereditary
How does HUS preset?
E coli O157:H7 serotype
Period of risk of HUS
- Up to 14 days after onset of diarrhoea
- 15% develop HUS
Bloody diarrhoea is a medical emergency in children
What triad presents in HUS?
Microangiopathic haemolytic anaemia
Thrombocytopenia
Acute Kidney Injury / Acute Renal Failure
How is bloody diarrhoea and HUS managed?
Prevention of oliguric HUS = intravascular volume expansion
What are the long term consequences of AKI?
- BP
- Proteinuria monitoring
- Evolution of CKD
How is HUS managed (same as all AKI)?
3Ms
Monitor
5 kidney functions
Fluid balance - hypertension
Electrolytes (monitor for hyperkalaemia)
Acidosis (excess urea)
Waste
Hormones - hypertension
Aware of other organs
Maintain
IV normal saline and fluid
Renal replacement therapy
Minimise
No antibiotics / NSAIDS
What are some chronic kidney disease causes ?
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
- 55% of paediatric CKD
- Reflux nephropathy
- Dysplasia
- Obstructive Uropathy (example - posterior urethral valves)
Hereditary conditions
- Cystic kidney disease (in adult is Autosomal dominant polycystic kidney disease)
- Cystinosis
Glomerulonephritis
CAKUT may not be isolated what should you be thinking of if it is not?
Think Syndromic
Turner
Trisomy 21
Branchio-oto-renal
Prune Belly syndrome
What is prune belly syndrome?
Prune-Belly syndrome, also known as Eagle-Barrett syndrome, is a rare disorder characterized by partial or complete absence of the stomach (abdominal) muscles, failure of both testes to descend into the scrotum (bilateral cryptorchidism), and/or urinary tract malformations.
At what GFR do you start to find signs and symptoms?
<60
Symptoms vary in CKD depending on what function of the kidney is affected?
Uraemic – loss of appetite, weight loss, itch
Water – polyuria
Salt / acid base – lethargy
Endocrine – lethargy, reduced effort tolerance, anaemia, HT, hypotensive if very polyuric
Bladder dysfunction - neuropathic bladders such as spina bifida
How is a UTI diagnosed?
Clinical signs PLUS
- Bacteria culture from midstream urine
- Any growth on suprapubic aspiration or catheter
What does a fever indicate in UTI often?
Pyelonephritis
What are the difference in in symptoms for younger and older age for a UTI?
Younger age more systemic symptoms
Older the age more lower tract symptoms
Also symptoms depends whether it is upper or lower tract
How is a urine specimen obtained?
Normal social cleanliness - water
Clean catch urine or midstream urine (if continent)
?? collection pads, urine bags (good at excluding infection but not the best for diagnosing because of the risk of contamination
of normal gram-negative bacteria found in the perineum and skin)
Sick infants = catheter samples or suprapubic aspiration (USS)
Acutely unwell - do not delay treatment
How is a UTI diagnosed?
Suggestive tests
- Dipstix
Leucocyte esterase activity, nitrites
unreliable < 2 yrs of age
Microscopy
Pyuria
Bacturia
GOLD STANDARD:Culture > 105 Colony forming units/ml
- Gram negative bacteria - E.coli
Why are UTIs a worry?
In the context of VESICO-URETERIC REFLUX may cause a kidney injury
Grades 1-5
High grade/bilateral (??renal dysplasia)
The combination of a vulnerable kidney, UTI & VUR can result in?
SCARRING
(Papilla shape – concave associated with intra renal reflux and found in the renal poles the most common place for renal scaring)
In UTI what are the principle things we are looking for and what guidelines are there on who to investigate?
Principles:
Congenital vs. acquired
- Screening for children at risk of progressive scaring (Reflux nephropathy) & Capture those with renal dysplasia
- Urological abnormalities
- Unstable bladder-Voiding dysfunction
Guidelines who to investigate:
Upper tract symptoms
Younger
Recurrent
What investigations are done in a worrying renal case of UTI?
USS within 6 weeks-structure
DMSA (isotope scan)
Scaring / function
Micturating cysto-urethrogram (GOLD STANDARD FOR REFLUX)
MAG 3 scan-dynamic
What is the treatment for UTI?
Lower tract
3 days oral antibiotic
Upper tract / pyelonephritis
antibiotics for 7-10 days
- Oral if systemically well
Role of prophylaxis ?? (done if have abnormal urinary tract)
Prevention-Fluids, hygiene, constipation
Manage voiding dysfunction
What are key factors that affect the progression of CKD?
- HT
- Proteinuria
High intake of protein, phosphate and salt
Bone health
- PTH
- Phosphate
- Vitamin D
Acidosis
Recurrent UTIs
What is the gold standard for assessing BP?
Sphigmanomter
- Doppler (<5yrs)
Oscillomerty
Technique
Bladder size
- NEVER use cuff too small
White coat effect-24 hour Ambulatory Blood Pressure Monitors
What factors affect BP?
Sex, Age & Height specific
What is the definition of HT in paediatrics?
3 occasions
Hypertension:
≥95th percentile
Borderline
≥90 but <95th pc
How is CKD managed?
Depends on what function is affected:
Waste – urea – nutrition / protein intake / minimise weight loss (catabolism)
Water – polyuria or oliguria
Salt – salt loosing / high potassium - low potassium diet / avoid hypercalcaemia / reduce phosphate in diet
Acid base – bicarbonate loss
Anaemia-EPO
Relax bladder function-Oxybutynin?
How does metabolic bone disease occur?
Kidneys wee out phosphate
High phosphate —– increase PTH
Kidneys activate Vitamin D3
(High PTH causes metabolic bone disease and cardiovascular disease)
(Most potent driver for PTH is Hypocalcaemia)
How is metabolic bone disease treated?
Treatment Principles
- Low phosphate diet
- Phosphate binders
- Active Vitamin D
If ongoing poor growth=Growth hormone
What is the CV risk from CKD?
Accelerated atherosclerosis
Traditional risk factors
PLUS Anaemia / metabolic bone disease (PTH)
What are results of and predictors of ongoing kidney injury?
Proteinuria and HT
What conditions are important from a paediatric perspective in terms of proteinuria/haematuria, AKI & CKD?
Proteinuria / Haematuria
- Glomerular disease
Nephrotic Syndrome
Nephritic Syndrome
Acute Kidney Injury
Haemolytic Uraemic Syndrome
Chronic Kidney Disease
- Developmental anomalies (CAKUT)
- Reflux nephropathy
How much of your kidney function do you need to lose before your creatinine starts to become abnormal?
40%
What is BP ideally controlled using?
ACEIs
In UTIs what should be considered?
Reflux nephropathy-reduce recurrent injury
Monitor for Upper tract symptoms/Younger/Recurrent UTIs
