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? [2]

Answer 2

Nephritic = High haematuria & intravascular overload

Nephrotic = High proteinuria & intravascular depletion

Question 3

What would Nephrotic syndrome look like? [5]

Pathophysiology [2]

Answer 3

Edema in face, legs, ascites and pleural effusions
Hypoalbuminemia
~Raised BP
Frothy Urine
~Pale - third space loss

Pathophys: a drop in oncotic pressure creates increased proteinuria [1] and intra-vascular depletion with fluid loss into the third space [1]

Question 4

What causes Nephrotic Syndrome? [2]

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? [4]

Answer 5

Urinalysis (proteinuria +++)
Urine protein creatinine ration >250mg/mmol
24h urine collection - gold standard
U&E, Cr, albumin

Question 6

Why don’t we biopsy in most nephrotic syndromes? [1]

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?
Common [4]
Uncommon [2]
Long term prognosis of nephrotic syndrome [1]

Answer 7

Commonest:
GI upset 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? [2]

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? [1]

Answer 9

Second line immunosuppression

Question 10

Try to list 8 major causes of childhood haematuria? [3] + [5] that cause hematuria

Answer 10

UTI
Trauma
Stones

Glomerulonephritis due to:

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

Question 11

What’s the classic presentation of Nephritic Syndrome? [7]

Answer 11

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

Often comes post-infection, particularly throat

Question 12

What’s the most common nephritic syndrome in kids vs adults? [2]

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 and treat IgA nephropathy?

Answer 17

Clinical diagnosis 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, prednisolone for GI sx

ACEI Ramipril for kidneys

Long term monitor for HTN & Proteinuria

Question 20

Which Glomerulonephritidis affect which layer of the Glomerular Filtration BArrier?

Answer 20

Podocytes = MCD & SLE

GMB = Membranous & Post-infective (PIGN)

Endothelial cells = PIGN, HUS, Membranoproliferative glomerulonephritis or SLE

mesangial = HSP, IgA nephropathy or SLE

Question 21

Management of acute post-infective GN

Answer 21

Penicillin
Diuretics
NOT ACEi as can cause AKI

Question 22

Haemolytic uremic syndrome
Epidemiology
Aetiology [2]
Presentation [2]

Answer 22

Ep: <5y/o in outbreaks of contaminated undercooked meat
Ax: secondary to infection with E. coli O157 shiga like-toxin (also strep pneumoniae, HIV) or primary immune dysregulation

Presentation: starts with colitis then hemoglobinuria then oliguria
- CNS signs then encephalopathy > coma

Question 23

Haemolytic uremic syndrome

Pathophysiology [4]

Answer 23

• microangiopathic haemolytic anaemia (intravascular haemolysis and red cell fragmentatation).
• Endothelial damage triggers:
  > thrombosis, platelet consumption (causing thrombocytopenia)
  > fibrin deposition in the glomeruli
  > causing AKI

Question 24

Haemolytic uremic syndrome
Investigations [3] - what would you see on routine bloods? [5]
Mx [2]

Answer 24

FBC, blood film (normochromic normocytic anaemia, schistocytes, burr cells, elevated WCC, thrombocytopenia)
U&E, Cr (reduced GFR)
LDH raised
Coombs test negative

Mx:

• Supportive (blood transfusion, fluid & electrolyte balance, RRT)
• Plasma exchange if severe