Nephritic & Nephrotic Syndrome

Question 1

What are the 3 layers of the Glomerular Filtration Barrier?

Answer 1

Endothelial Cell layer - fenestrated
GBM - Type 4 collagen & laminin with embedded mesangial cells (smooth muscle)
Podocytes (Podocin & nephrin proteins)

Question 2

Define Nephritic vs Nephrotic Syndrome?

Answer 2

Nephritic = High haematuria & intravascular overload

Nephrotic = High proteinuria & intravascular depletion

Question 3

What would Nephrotic syndrome look like?

Answer 3

OEdema in face, legs, ascites and pleural effusions

~Raised BP

Frothy Urine

~Pale but mostly well

Question 4

What causes Nephrotic Syndrome?

Answer 4

85% are Minimal Change Disease

15% are termed “Steroid REsistant nephrotic syndrome” which includes:

• Congenital NPHS1 or 2
• Acquired FSGS (Focal segmental glomerular sclerosis)

Question 5

How do we confirm minimal change disease?

Answer 5

U&Es + Creatinine = Renal function should be normal
BP = Generally Normal
Urine Dipstix = high Protein & maybe haematuria

Trial Prednisalone

Question 6

Why don’t we biopsy in most nephrotic syndromes?

Answer 6

Most it’s almost always minimal change disease so we just trial treatment

Question 7

Nephrotic Syndrome is treated with 8wks of prednisolone. what are the major SEs?

Answer 7

Commonest:
GI due to high acid
Behaviour (irritable/moody/don't sleep)
HTN
Weight Gain

Uncommon:
Glucose intolerance
Adrenal crisis

Growth problems with recurrent courses

Question 8

Describe the outcome of MCD?

Answer 8

95% go into remission in 2-4wks

80% will relapse

Question 9

How do you treat Steroid Resistant Nephrotic Syndromes e.g. FSGS?

Answer 9

Second line immunosuppression

Question 10

Try to list 8 major causes of childhood haematuria?

Answer 10

Glomerulonephritis due to:

• Post-infective GN
• IgA nephropathy / HSP
• Membranoproliferative GN
• SLE
• ANCA +ve vasculitis e.g. GPA

UTI
Urethritis
Trauma
Stones

Question 11

What’s the classic presentation of Nephritic Syndrome?

Answer 11

• Haematuria (frank or microscopic)
• Proteinuria
  Reduced GFR:
  –> Oligura
  –> Fluid overload (JVP/oedema)
  –> hypertension
  –> High creatinine

history of abdominal pain, pyrexia and vomitting

Often comes post-infection, particularly throat

Question 12

What’s the most common nephritic syndrome in kids vs adults?

Answer 12

Kids - Post-infective Glomerulonephritsi

Adults – IgA Nephropathy

Question 13

What causes Post-infective Glomerulonephritis?

Answer 13

Group A strep
Throat infections 7-10days later
skin 2-4wks later

Nephrogenic strep antigens bind to sites in glomeruli & form immune complexes which are deposited there

This triggers Alternative Complement activation & Adaptive immune response leading to the nephritis

Question 14

How can you diagnose Post-infective Glomerulonephritis?

Answer 14

A bacterial culture & throat swab for Strep A

+ve ASO Titre

Low C3 (used up)

Normal Renal US

ANA (SLE) + ANCA (GPA) to rule out autoimmune

Question 15

So child with nephritic syndrome presents a week after having a throat infection.
Tests show Strep A culture, +ve ASO titre, low C3
Renal US, ANA & ANCA were all -ve
How would you treat the kid?

Answer 15

Diagnosis of Post-infective GN

Abx
Diuretic for fluid overload
Support renal function (e.g. restrict fluid, restrict Na, ACEI etc)

It will be self-limiting

Question 16

IgA nephropathy is a commoner cause of nephritic syndrome in older kids/adults. What causes it?

Answer 16

Often comes 1-2days post or during an URTI (So much quicker than post-infective GN)

Question 17

How do you diagnose (chronic or acute?)

and treat IgA nephropathy?

Answer 17

Clinical diagnosis:
Recurrent -macroscopic haematuria
Chronic- microscopic haematuria

with biopsy to confirm

ACEI!
If severe give Immunosuppression

Question 18

What is IgA Vasculitis / HSP?

Answer 18

Henoch-Sholein Purpura

It’s very similar to IgA nephropathy but comes with more systemic problems. You need Palpable purpura + 1 of

• Renal involvement
• Abdo pain
• Arthritis
• Renal biopsy showing IgA deposits

Again it comes 1-3days post viral URTI

Question 19

How do you treat HSP/IgA vasculitits?

Answer 19

Symptomatic treatments for joint/gut symptoms e.g. analgesia & NSAIDs

CCS may help gut

Immunosuppression if severe

ACEI for kidneys

Long term monitor for HTN & Proteinuria

Question 20

Which Glomerulonephritidis affect which layer of the Glomerular Filtration BArrier?

Answer 20

Podocytes = MCD ,
FSGS,
lupus

GMB = Membranous & Post-infective (PIGN),
MPGN (membrane proliferative glomerulonephritis)

Endothelial cells =
 PIGN,
 HUS, 
MPGN (membrane proliferative glomerulonephritis), lupus,
 ANCA vasculitis

mesangial =
HSP,
IgA nephropathy,
Lupus

Question 21

MCD presenting symptoms

Answer 21

Age 1 - 10
Normal blood pressure
No Frank haematuria
Normal renal function

Question 22

what atypical symptoms should you see in MCD, to consider a renal biopsy?

Answer 22

Suggestions of autoimmune disease
Abnormal renal function
Steroid resistance

Question 23

what is Nephrotic syndrome?

Answer 23

proteinuria
hypoalbuminia
Oedema
(usually no haematuria)

Question 24

How to measure proteinuria?

Answer 24

1. Dipstix- easiest- but can give false positives and negatives
   ≥ 3+ usually abnormal
2. Protein Creatinine Ratio (practical)
   Early morning urine (best)
   normal: Pr:CR ratio <20mg/mmol
   Nephrotic range: >250mg/mmol
3. . 24hr urine collection (gold standard)
   normal <60mg/m²/24hrs
   Nephrotic range>1g/m²/24hrs
   Adults >3.5g/24hrs

Question 25

Pathogenesis of nephrotic syndrome?

Answer 25

Interaction between lymphocytes (T and B cells) and podocytes

Question 26

what is acquired Steroid Resistant Nephrotic Syndrome from?

Answer 26

Podocyte loss

Progressive inflammation and sclerosis

Question 27

what genes are involved in congenital steroid resistant nephrotic syndrome?

pathogenesis?

Answer 27

NPHS1 – nephrin
NPHS 2 – podocin

podocyte loss

Question 28

when is it glomerular disease?

Answer 28

proteinuria(!!!) and haematuria

Question 29

Glomerulonephritis pathogenesis- from group A strep

Answer 29

1. Antigen “Mimicry”

2. Ab-Ag complexes