Paediatric Nephrology - Nephrotic Syndrome

Question 1

What are 3 broad categories of kidney disease?

Answer 1

Glomerular disease
AKI
Chronic kidney disease

Question 2

What are the subtypes of glomerular disease and how are they recognised?

Answer 2

Nephrotic Syndrome - Proteinuria

Nephritic Syndrome - Haematuria

Question 3

What occurs in an AKI?

Answer 3

Haemolytic Uraemic Syndrome

Question 4

How much of the cardiac output goes to the kidneys?

Answer 4

Receives 25% cardiac output/min

Question 5

What are the GFRs of neonates and adults?

Answer 5

Neonate - 20-30ml/min/1.73m²

Age 2yrs equals adult - 90-120

Question 6

What are the 5 kidney functions?

Answer 6

Waste handling

Water handling

Salt balance

Acid base control

Endocrine
-red cells/blood pressure/bone health

Question 7

What are the features of the endothelial cells in the glomerular filtration barrier?

Answer 7

Fenestrated

Vulnerable to immune mediated injury

Question 8

What are the features of the glomerular basement membranes in the glomerular filtration barrier?

Answer 8

2 proteins - Type IV collagen (COL4) and laminin
Synthesis from podocytes and endothelial cells
Mesangial cells playing a role in turnover

Question 9

What are the features of the podocytes in the glomerular filtration barrier?

Answer 9

Proteins

-Podocin, nephrin

Question 10

What are the features of the mesangial cells in the glomerular filtration barrier?

Answer 10

Glomerular structural support
Embedded in GBM
Regulates blood flow of the glomerular capillaries

Question 11

How do patents with kidney problems present?

Answer 11

Proteinuria, haematuria

Question 12

What does proteinuria indicate?

Answer 12

Glomerular injury

Question 13

What do increasing haematuria and intravascular overload indicate?

Answer 13

Nephritic syndrome

Question 14

What do increasing proteinuria and intravascular depletion indicate?

Answer 14

Nephrotic syndrome

Question 15

What are the 2 broad types of glomerulopathy?

Answer 15

Acquired and congenital

Question 16

In acquired glomerulopathy, how may each component of the glomerular filtration barrier be affected?

Answer 16

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

Question 17

In congenital glomerulopathy, how may each layer of the glomerular filtration barrier be affected?

Answer 17

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)

Question 18

How does a dipstick measure proteinuria and what is an abnormal measurement?

Answer 18

Measures concentration
≥ 3+ usually abnormal
False positives and negatives

Question 19

What is a normal protein creatinine ratio and what is the nephrotic range?

Answer 19

Early morning urine (best)

Normal: Pr:CR ratio <20mg/mmol

Nephrotic range: >250mg/mmol

Question 20

In a 24hr urine collection, what are the normal and abnormal protein levels?

Answer 20

GOLD STANDARD

Normal <60mg/m²/24hrs

Nephrotic range>1g/m²/24hrs
(Adults >3.5g/24hrs)

Question 21

What is nephrotic syndrome?

Answer 21

Nephrotic range proteinuria

->

Hypoalbuminaemia

->

Oedema (increasing 3rd space fluid volume)

Question 22

How are Starling’s Forces relevant in proteinuria?

Answer 22

Oncotic (Osmotic) vs. Hydrostatic
Protein (Osmotic)
“magnet to water”

Question 23

What may a typical paediatric nephrotic syndrome look like?

Answer 23

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

Question 24

What might you see when examining a nephrotic child?

Answer 24

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

Question 25

What are findings that indicate nephrotic syndrome?

Answer 25

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

Question 26

What are the typical and atypical features of nephrotic syndrome?

Answer 26

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

Question 27

How is nephrotic syndrome treated?

Answer 27

If typical features
-Prednisolone 8 weeks

Side effects from high dose glucocorticoids - CUSHING’S

Question 28

What are potential paediatric glucocorticoid side effects?

Answer 28

Behaviour

Mood lability

Sleep disturbance

Infection risk

• Varicella status
• Pneumococcal vaccination
• Antibiotic prophylaxis

Question 29

What percentage of idiopathic NS in childhood is steroid resistant?

Answer 29

10%

Question 30

What are the types of steroid sensitive NS?

Answer 30

Non-relapsing
Infrequently relapsing
Frequently relapsing
Steroid dependent

Question 31

What is the pathogenesis in NS?

Answer 31

Interaction between lymphocytes (T and B cells) and podocytes

Question 32

What are the outcomes of NS?

Answer 32

Remission - 95% in 2-4 weeks
Relapse - 80%
80% long term remission

Question 33

What is the second line of therapy in nephrotic syndrome?

Answer 33

Immunosuppression

Question 34

What is the acquired type of steroid-resistant NS?

Answer 34

Focal Segmental Glomeruloscerosis (FSGS)

• Podocyte loss
• Progressive inflammation and sclerosis

Question 35

What are the congenital types of steroid-resistant NS?

Answer 35

Infant presentations
NPHS1 – nephrin
NPHS 2 – podocin
Podocyte loss