Paediatric Nephrology Flashcards
Part 1
what is glomerular disease?
Glomerular disease is a disorder of the kidneys, in which the normal functioning of the kidneys is disturbed and the chemical balance is not maintained in your blood and urine
what are the 2 main types of glomerular disease?
The two basic types of glomerular disease include nephritic and nephrotic, but, with some diseases, the two types can overlap
The key feature of nephritic disease (“glomerulonephritis”) is blood in the urine (hematuria)
People with nephrotic syndrome have protein in the urine (proteinuria) but, often, little to no blood in the urine (hematuria)
what is teh strucutre of the nephron?
- Receives 25% cardiac output/min
- GFR:
- neonate 20-30ml/min/1.73m²
- Age 2yrs equals adult 90-120
(Don’t have normal kidney function at birth)
glomerular disease cn be caused in 2 main way - what are they?
congenital
aquired
what are the 5 kidney functions?
- Waste handling (urea/creatinine)
- Water handling
- Salt balance (sodium/potassium/calcium/phosphate)
- Acid base control (bicarbonate)
- Endocrine - red cells/blood pressure/bone health
what makes up the Glomerular Filtration barrier?
- Endothelial cell - Fenestrated, Vulnerable to immune mediated injury
- GBM - Synthesis from podocytes and endothelial cells, Mesangial cells playing a role in turnover
- Podocyte - Proteins
- Mesangial cells - Glomerular structural support, Embedded in GBM, Regulates blood flow of the glomerular capillaries
This barrier has three major components: what are they?
the fenestrated endothelial cell, the glomerular basement membrane (GBM), and the podocyte with their “slit diaphragms”
what are the main things patients present with with glomerular disease?
Haematuria and Proteinuria
Glomerulopathy:
•Blood and protein in varying amounts dictate:
- Clinical _________
- Suggests ______
- However - Injury to one part of the GFB affects the other ________
- Take home message - _________ signifies glomerular injury
presentation
diagnosis
components
Proteinuria
does haematuria and proteinuria indicate nephrotic or nephritic syndrome?
Acquired Glomerulopathy is common
what commonets are affected?
(Acquired more common than congenital in paediatrics)
- Epithelial cell (podocyte) - Minimal Change Disease
- Basement Membrane - Post Infectious Glomerulonephritis (PIGN)
- Endothelial cell - PIGN, Haemolytic Uraemic Syndrome (HUS)
- Mesangial cell - HSP / IgA nephropathy
Congenital Glomerulopathy is rare
what layers may be affected?
- Podocyte cytoskeletal integrity - Congenital nephrotic syndrome
- Basement membrane proteins - Alport syndrome (XL), Thin basement membrane disease (AD)
- Endothelial/microvascular integrity - Complement regulatory proteins (MPGN)
Proteinuria - How much is too much?
Dipstix - Measures concentration, ≥ 3+ usually abnormal
Protein Creatinine Ratio (practical) - Early morning urine (best), normal: Pr:CR ratio <20mg/mmol, Nephrotic range: >250mg/mmol
24hr urine collection (gold standard) - normal <60mg/m²/24hrs, Nephrotic range>1g/m²/24hrs
What is Nephrotic Syndrome
Nephrotic range proteinuria = Hypoalbuminaemia = Oedema increasing 3rd space fluid volume
Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling
the low level of protein in the blood reduces the flow of water from body tissues back into the blood vessels, leading to swelling
how does proteinuria cause oedema?
Starling’s forces - Oncotic (Osmotic) vs. Hydrostatic - Protein (Osmotic) = “magnet to water”
no solutes or proteins in the vascular compartment to hold the water so the water moves to the interstitium resulting in peripheral oedema e.g. sweeling of feet
also causes decereased volume in circulation meaning decreased venous return to the heart meaning decereased in renal blood flow and then decreased in GFR
Nephrotic syndrome:
Diagnosis easy once you have clinical presentation
what would ou seen on presentation?
- Oedema
- Proteinuria
50% of children presenting with minimal change disease have microscopic haematuria
low albumin
Urine Na – 10mmol/l - if less then 20 then means your holding onto water
Serum creatinine will be in the normal range in uncomplicated nephrotic syndrome, such as that occurring in minimal-change nephropathy
What type of nephrotic syndrome are common at different age of presentation?
Minimal change is steroid sensitive but if steroid resistant then think about FSGS and MCGN
80% of children will have minimal change disease
Nephrotic Syndrome- MCD - what are the typical and atypical features?
- Typical Features - Age 1 - 10 (2-5yrs most common age range), Normal blood pressure, No Frank haematuria, Normal renal function
- Atypical features - Suggestions of autoimmune disease, Abnormal renal function, Steroid resistance
Only then consider renal biopsy
Clinical diagnosis
Don’t biopsy in MCD
what is Nephrotic syndrome Treatment?
- If typical features
- Prednisolone 8 weeks
- Side effects from high dose glucocorticoids
More readily response to steroid, more likely you have ___
MCD
what is the outcome of nephrotic syndrome?
- Remission - 95% in 2-4 weeks
- Relapse - 80%
- 80% long term remission
- Don’t do harm before good! - Second line immunosuppression - Steroid dependant and frequent relapses (>4 relapses/year) – on steriods more than they arnt and that’s when you use second line therapies
Steroid Resistant Nephrotic Syndrome - whata re the causes?
•Acquired - Focal Segmental Glomeruloscerosis (FSGS) = Podocyte loss and Progressive inflammation and sclerosis
Acquired cause is more common
50% of children with FSGS will need renal replacement therapy in 5 years
•Congenital - Infant presentations, NPHS1 – nephrin , NPHS 2 – podocin, Podocyte loss
when do you investigate haematuria?
- Macroscopic /Frank - Investigate
- Microscopic – Dipstix adequate - Investigate if > trace on 2 occasions
- Haemaglobinuria - stix positive + microscopy negative - Associated proteinuria = glomerular disease
whata re the cuases of haematuria?
what are the signs and symptoms of nephritic syndrome?
- Haematuria and proteinuria
- Reduced GFR:
- Oliguria
- Fluid overload - Raised JVP, oedema
- Hypertension
- Worsening renal failure = Rapidly Progressive GN
•Intrarenal cause of Acute kidney injury (AKI)
how is a diagnosis of nephritic syndrome made?
•Clinical diagnosis - describes glomerulonephritis
what is Acute Post-Infectious Glomerulonphritis?
Acute post streptococcal glomerulonephritis is an immunologic response of the kidney to infection, characterized by the sudden appearance of edema, hematuria, proteinuria and hypertension . It is essentially a disease of childhood that accounts for approximately 90% of renal disorders in children
PSGN is a kidney disease that can develop after infections caused by bacteria called group A Streptococcus (group A strep)
•Age of onset – 3-5 most common
what causes acute post infection glomerulonephritis?
- Usually Group A Strep
- Beta hemolytic
- Site - throat 7-10 days, Skin 2-4 weeks
what is the pathogenesis of Acute Post-Infectious Glomerulonphritis?
Pathogenesis:
- Antigen “Mimicry”
- Ab-Ag complexes
what is the treamtent of Acute Post-Infectious Glomerulonphritis?
Self limiting
Treatment is focused on relieving symptoms
- Antibiotic (should be used to treat any bacterial infection)
- Support renal functions - Electrolyte/acid base
- Overload/hypertension - Diuretics (Blood pressure medications and diuretic medications may be needed to control swelling and high blood pressure)
- Outcome (usually very good) - Not recurrent
what is IgA Nephropathy?
a condition that damages the glomeruli inside your kidneys and can cause kidney disease
The immune response is what affects your kidneys
IgA nephropathy occurs when IgA protein gets stuck in kidneys causing inflammation. The inflammation causes your kidneys to leak blood and protein (usually immediately) and over the course of many years, your kidneys can lose function and lead to kidney failure
- Most common glomerulonephritis
- 1-2 days after URTI
- Usually older children and adults
what are the signs of IgA nephropathy?
- Recurrent macroscopic haematuria
- ± Chronic microscopic haematuria (between relapses)
- Varying degree of proteinuria
IgA nephropathy is a _______ diagnosis
clinical
- Negative autoimmune workup
- Normal compliment
- Confirmation Biopsy
what is the treatment of IgA nephropathy?
- Mild disease - proteinuria with ACEi (These are blood pressure medications used to reduce protein loss and control blood pressure)
- Moderate to Severe disease - immunosuppresion (KDIGO) (These medications are used to calm your immune system (your body’s defense system) and stop it from attacking your glomeruli)
what is Henoch Schonlein Purpura IgA related vasculitis?
- Age of onset : 5-15yrs
- Clinical diagnosis
- Mandatory palpable purpura
- one of 4
- Abdominal pain
- Renal involvement
- Arthritis or arthralgia
- Biopsy - IgA depostition
IgA Vasculitis- what causes it and how long does it last?
- 1-3 days post trigger - Viral URTI in 70%, Streptococcus, drugs can trigger IgA
- Duration of symptoms - 4-6 weeks, 1/3rd relapse
- Nephritis - Mesangial cell injury
what is the treatment of IgA Vasculitis?
- Symptomatic - Joints, gut
- Glucocorticoid therapy
- Immmunosuppresion
The disease usually goes away on its own. However, your health care professional may suggest certain medicines to relieve symptoms such as abdominal pain, joint pain, and swelling. If your kidneys are involved, the treatment goal will be to prevent CKD
part 3
what is Acute Kidney Injury (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”
- Anuria/oliguria (<0.5ml/kg/hr)
- Hypertension with fluid overload
- Rapid rise in plasma creatinine
what is calssified as a AKI?
- Serum creatinine: > 1.5x age specific reference creatinine (or previous baseline if known)
- Urine output <0.5 ml/kg for > 8hours
- Interpretation of AKI warning score:
- 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 is AKI management?
- Prevention
- 3 Ms
- Monitor - Paediatric Early Warning Scores(BP) (Resp rate, Saturations, Heart rate, BP, Temperature), Urine Output, weight
- Maintain - good hydration/electrolytes/acid - base
- Minimise - Drugs (can cause further kidney injury)
what are the 3 different classifications of causes of AKI?
Pre-renal, renal and post renal
Causes of Acute Kidney injury - What are pre-renal causes?
•Perfusion problem
Volume depletion
Oedematous states
Hypotension
Renal hypoperfusion - Drugs, renal artery stenosis or occlusion, Hepato-renal syndrome
Causes of Acute Kidney injury - what are intrinsic renal problems?
- Glomerular disease - HUS, Glomerulonephritis
- Tubular injury - acute tubular necrosis (ATN) due to Consequence of hypoperfusion andDrugs
- Interstitial nephritis - NSAID, autoimmune
Causes of Acute Kidney injury - what are post renal causes?
obstructive uropathies
what is the defnition of Haemolytic Uraemic Syndrome?
Haemolytic-Uraemic Syndrome - when does it occur?
•Typical HUS:
post diarrhoea - Entero-Haemorrhagic E.coli (EHEC)
- Other causes - pneumococcal infection, drugs
- Atypical HUS – pattern of haemolysis, thrombocytopenia and AKI and in absence of obvious cause then think of this, genetic system resulting in over activation of the alternative complement pathway
how does HUS present?
- 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 is the triad seen in Haemolytic-Uraemic Syndrome?
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Acute Kidney Injury / Acute Renal Failure
Management of bloody diarrhoea and HUS:
Prevention of oliguric HUS = ???
Prevention of oliguric HUS = intravascular volume expansion
Once you have HUS, management is the same as all AKI
Haemolytic-Uraemic Syndrome - what are the 3 Ms
Monitor:
- 5 kidney functions - Fluid balance - hypertension, Electrolytes, Acidosis, Waste, Hormones - hypertension
- Aware of other organs
Maintain:
- IV normal saline and fluid
- Renal replacement therapy
Minimise:
•No antibiotics/NSAIDS
what are the long term consequences of AKI?
(Applies for all causes of AKI)
- Blood pressure
- Proteinuria monitoring
- Evolution to CKD
Part 4
what is CKD?
Chronic Kidney Disease - what are the main 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 - 17% , Cystic kidney disease, Cystinosis
Glomerulonephritis - 10%
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) may not be isolated, it may be syndromic
what are some examples?
- Turner
- Trisomy 21
- Branchio-oto-renal
- Prune Belly syndrome
what ar ethe stages of CKD
<60 start to find signs and symptoms
Presentation of CKD - the symptoms are variable depending what?
Symptoms variable depending which function affected
what is the defnition of a UTI?
- Clinical signs PLUS
- Bacteria culture from midstream urine
- Any growth on suprapubic aspiration or catheter
Clinical Findings
upper vs lower tract
Principle:
- younger the age more systemic symptoms
- older the age more lower tract symptoms
Upper tract symptoms circled
Obtaining Urine Specimen- how should it be done?
- Normal social cleanliness - water
- Clean catch urine or midstream urine
- Sick infants - catheter samples or suprapubic aspiration (USS)
- Acutely unwell - do not delay treatment
how is a diagnosis of UTI made?
- Dipstix - unreliable < 2 yrs of age
- Microscopy - UTIs can be found by analyzing a urine sample. The urine is examined under a microscope for bacteria or white blood cells, which are signs of infection
- Culture > 10<span>5</span> Colony forming units/ml
So why worry about UTIs? :
What is Vescico-Ureteric Reflux?
VUR causes urine to flow back up through the urinary tract, often leading to urinary tract infections. VUR can cause urinary tract infections (UTI) and, less commonly, kidney damage
when the flow of urine goes the wrong way. This condition is more common among infants and young children
what are the grades of VUR?
What are we looking for?
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 invesitgations can be done?
- Ultrasound- structure
- DMSA (isotope scan) - Scaring/function
- Micturating cysto-urethrogram, MAG 3 scan -dynamic
how do we treat UTI?
- Lower tract - 3 days oral antibiotic
- Upper tract/pyelonephritis - antibiotics for 7-10 days (Oral if systemically well), Role of prophylaxis ??
- Prevention - Fluids, hygiene, constipation
- Manage voiding dysfunction
what are Factors affecting progression of CKD?
•Late referral
•Hypertension
•Proteinuria
- High intake of protein, phosphate and salt
- Bone health
- Acidosis
- Recurrent UTIs
how can you measure blood pressure?
- Gold standard - Sphigmanomter
- Doppler (under age 5)
- NEVER use cuff too small
- White coat effect - 24 hour Ambulatory Blood Pressure
Blood Pressure Chart:
Factors affecting BP = sex, age, height specific
what is the defnition fo hypertension?
- 3 occasions
- Hypertension: ≥95th percentile
- Borderline ≥90 but <95th pc
Management of CKD:
Variable depending on what?
which function affected
Metabolic bone disease is a common complication of chronic kidney disease (CKD)
how is it caused?
- Kidneys wee out phosphate
- High phosphate = increase PTH
High PTH causes metabolic bone disease and cardiovascular disease
Kidneys activate Vitamin D3
- Treatment Principles - Low phosphate diet, Phosphate binders, Active Vitamin D
- If ongoing poor growth - Growth hormone
what is the cardiovascular risk?
- Accelerated atherosclerosis
- Traditional risk factors PLUS Anaemia/metabolic bone disease (PTH)
(Traditional – hypertension, smoking, diabetes, dyslipidaemia, obesity)
Take home messages:
- Acute kidney injury predisposes to CKD
- Proteinuria and hypertension - Result of and predictor of ongoing kidney injury, Manage 5 renal functions
- UTI - Reflux nephropathy – reduce recurrent injury, Monitor for Upper tract symptoms/Younger/Recurrent UTIs, Limited place for prophylaxis
