Paediatric Nephrology - Nephrotic Syndrome Flashcards
What are 3 broad categories of kidney disease?
Glomerular disease
AKI
Chronic kidney disease
What are the subtypes of glomerular disease and how are they recognised?
Nephrotic Syndrome - Proteinuria
Nephritic Syndrome - Haematuria
What occurs in an AKI?
Haemolytic Uraemic Syndrome
How much of the cardiac output goes to the kidneys?
Receives 25% cardiac output/min
What are the GFRs of neonates and adults?
Neonate - 20-30ml/min/1.73m²
Age 2yrs equals adult - 90-120
What are the 5 kidney functions?
Waste handling
Water handling
Salt balance
Acid base control
Endocrine
-red cells/blood pressure/bone health
What are the features of the endothelial cells in the glomerular filtration barrier?
Fenestrated
Vulnerable to immune mediated injury
What are the features of the glomerular basement membranes in 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?
Proteins
-Podocin, 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 do patents with kidney problems present?
Proteinuria, haematuria
What does proteinuria indicate?
Glomerular injury
What do increasing haematuria and intravascular overload indicate?
Nephritic syndrome
What do increasing proteinuria and intravascular depletion indicate?
Nephrotic syndrome
What are the 2 broad types of glomerulopathy?
Acquired and congenital
In acquired glomerulopathy, how may each component of the glomerular filtration barrier be affected?
COMMON
Endothelial cell
-PIGN, Haemolytic Uraemic Syndrome (HUS)
Basement Membrane
-Post Infectious Glomerulonephritis (PIGN)
Epithelial cell (podocyte) -Minimal Change Disease
Mesangial cell
-HSP/IgA nephropathy
In congenital glomerulopathy, how may each layer of the glomerular filtration barrier be affected?
Podocyte cytoskeletal integrity
-Congenital nephrotic syndrome (Proteins - Podocin (AR), nephrin (AR))
Basement membrane proteins
- Alport syndrome (XL)
- Thin basement membrane disease (AD)
Endothelial/microvascular integrity
-Complement regulatory proteins (MPGN)
How does a dipstick measure proteinuria and what is an abnormal measurement?
Measures concentration
≥ 3+ usually abnormal
False positives and negatives
What is a normal protein creatinine ratio and what is the nephrotic range?
Early morning urine (best)
Normal: Pr:CR ratio <20mg/mmol
Nephrotic range: >250mg/mmol
In a 24hr urine collection, what are the normal and abnormal protein levels?
GOLD STANDARD
Normal <60mg/m²/24hrs
Nephrotic range>1g/m²/24hrs
(Adults >3.5g/24hrs)
What is nephrotic syndrome?
Nephrotic range proteinuria
->
Hypoalbuminaemia
->
Oedema (increasing 3rd space fluid volume)
How are Starling’s Forces relevant in proteinuria?
Oncotic (Osmotic) vs. Hydrostatic
Protein (Osmotic)
“magnet to water”
What may a typical paediatric nephrotic syndrome look like?
Jessica age 2.5yrs
History
- Gastroenteritis 10days prior
- 3-4 days
- Swollen face (worse in mornings), one eye closed in mornings, legs
- No allergies
- Family Hx – great grandmother nephrectomy
What might you see when examining a nephrotic child?
Jessica cont.
Looked well, pale Inflated weight 14.9kg Periorbital oedema, pitting oedema legs, ascites, small pleaural effusions BP 98/56 (can be raised) Frothy urine
What are findings that indicate nephrotic syndrome?
Oedema
Proteinuria
- Urine dipstix
- protein 3+
- blood 2+ blood (not frank)
- Protein Creatinine Ratio – 1200mg/mmol creatinine
- Urine Na – 10mmol/l
Bloods
- Abumin low 12mg/dl (n>32)
- Normal creatinine
What are the typical and atypical features of nephrotic syndrome?
Typical Features
- Age 1 - 10
- 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
How is nephrotic syndrome treated?
If typical features
-Prednisolone 8 weeks
Side effects from high dose glucocorticoids - CUSHING’S
What are potential paediatric glucocorticoid side effects?
Behaviour
Mood lability
Sleep disturbance
Infection risk
- Varicella status
- Pneumococcal vaccination
- Antibiotic prophylaxis
What percentage of idiopathic NS in childhood is steroid resistant?
10%
What are the types of steroid sensitive NS?
Non-relapsing
Infrequently relapsing
Frequently relapsing
Steroid dependent
What is the pathogenesis in NS?
Interaction between lymphocytes (T and B cells) and podocytes
What are the outcomes of NS?
Remission - 95% in 2-4 weeks
Relapse - 80%
80% long term remission
What is the second line of therapy in nephrotic syndrome?
Immunosuppression
What is the acquired type of steroid-resistant NS?
Focal Segmental Glomeruloscerosis (FSGS)
- Podocyte loss
- Progressive inflammation and sclerosis
What are the congenital types of steroid-resistant NS?
Infant presentations
NPHS1 – nephrin
NPHS 2 – podocin
Podocyte loss
