Glomerulonephritis

Question 1

What is glomerulonephritis?

Answer 1

The term encompasses a number on condiions which are caused by pathology in the glomerulus, present with proteinuria or haematuria or both, are diagnosed by renal biopsy, cause CKD and can progress to kidney failure (except minimal change disease)

Question 2

OK so what do the terms nephrotic and nephritic refer to…?

Answer 2

The terms nephrotic and nephritic are used to group types of glomerulonephritis by their clinical syndrome/ presentation

THEY ARE NOT DISEASES IN THEMSELVES

Question 3

What is nephritic syndrome?

Answer 3

Remember it is a syndrome due to a disease of the glomerulus… a set of clinical features rather than a disease in itself

Nephritic syndrome is one of two clinical patterns seen in glomerular disease

Characterised by haematuria, proteinuria, HTN and oliguria

Can be focal OR diffuse

Question 4

Types of nephritic syndrome

Answer 4

1. IgA nephropathy = most common type in the world
2. Henoch-Schönlein purpura
3. Post-strep/ post infectious glomerulonephritis
4. Godpasture’s/ anti glomerular basement membrane disease
5. Rapidly progressive glomerulonephritis

Question 5

What is IgA nephropathy?

Answer 5

A type of disease of the glomerulus that cause nephritic syndrome OR nephrotic syndrom OR both… but is classified as nephritic

Presentation: painless haematuria, <2 days after URTI or GI infection

Classic = patient had an URTI/ GI infection now has brown urine OR recurrent epidosdes of frank haematuria

Pathophysiology: IgA gets stuck in glomerular capillary wall and activates compement >> glomerular destruction >> haematuria

Diagnosis: biopsy shows IgA within mesanguim

Used to be thought of as benign but actually 30-50% cases progress to ESRD

Question 6

5 year old has palpable purpuric rash, abdominal pain, kidney involvement and joint pain – thoughts?

Answer 6

Henoch-Schonlein purpura - most common vasculitis of childhood

Small vessel vasculitis - systemic variant of IgA nephropathy with IgA deposited in the skin, joints and gut as well as kidney

Can cause bloody diarrhoea and intussusception

Typically affects children —– risk of permanent kidney damage is more common in adults

Diagnosis: hx of prev. infection + raised ASO titre

Question 7

Why are ARBs/ ACEi used to treat IgA nephropathy?

Answer 7

Many cases progress to ESRD and cause HTN so important to control BP to prevent further damage to kidney and reduce protein

Question 8

Classical presentation of post-strep GN?

Answer 8

Commonly seen in children following strep throat, can also occur following skin infections such as impetigo

Plastically occurs two weeks after throat infection or 3–6 weeks after skin infection

Strict antigen is deposit in the Jamarius leading to immune complex formation and inflammation

50% asymptomatic, tea coloured urine, HTN >> headaches, oliguria, oedema, flank pain, flu-like symptoms

Question 9

What is Goodpasture’s disease? AKA anti-glomerular basement membrane disease

Answer 9

Uncommon autoimmune disease

Autoantibodies to type 4 collagen - present in glomerular basement membrane

Causes renal and lung disease

Presentation: AKI + pulmonary haemorrhage, anaemia, haematuria, oedema, joint pain, tachypnoea, crackles over lung bases

Question 10

What can cause rapidly progressive glomerulonephritis?

Answer 10

Goodpasture’s, vasculitis, lupus

Histology: crescentic glomerulonephritis is classical finding

Question 11

Allport syndrome

Answer 11

Familial nephritis - 85% of cases are x-linked

Haematuria, CKD, sensorineural hearing loss, ocular abnomalities

No treatment

Management: control BP, dialysis, kidney transplant

ESRD occurs around 16-37yrs

Particularly bad during pregnancy

Question 12

What is nephrotic syndrome

Answer 12

Triad of:

1. Loss of >3g protein in the wee over 24hrs
2. Loss albumin in blood <30g/L
3. Oedema

Question 13

Pathophysiology of nephrotic syndrome?

Answer 13

Podocytes, GBM and endotelial cells form the kidney filtration barrier

Damage to the podocytes allows protein through leading to nephrotic syndrome

Podocytes are negatively charged therefore repel the negatively charged proteins

Question 14

There are causes of primary nephrotic syndrome - what are they?

Answer 14

1. Minimal change - children are mini
2. Focal segmental - adults and kids, segment from both ages
3. Membranous glomerulopathy - common in adults

Question 15

What might be the only indication a patient has nephrotic syndrome?

Answer 15

Pitting oedema and frothy urine (due to proteins)

Question 16

How is nephrotic syndrome managed?

Answer 16

Reduce protein loss by reducing BP: ACEi/ ARB

Reduce oedema: loop diuretics, salt restriction, fluid restriction

Reduce hyperlipidaemia with statins

Aim for 0.5-1kg fluid loss/ day to reduce risk of rapid depletion and AKI

Steroids

Take renal biopsy to find cause - unless you’re suspecting minimal change disease as this clears up with steroids

Question 17

Complications of nephrotic syndrome

Answer 17

Thromboembolism: anti-thrombotic factors are weed out and the liver makes more prothrombotic factors due to hypoalbuminaemia

Infection

Hyperlipidaemia: liver responds to low oncotic pressure by producing lipoproteins

Question 18

Child has nephrotic syndrome, most common cause?

Answer 18

Minimal change

Mostly idiopathic, albumin gets out but immunoglobulins do not

Does not cause CKD

Cannot be seen under light microscope as change is minimal… use electron microscope which will show effacement of podocyte foot processes

Management: prednisolone for 4-16 weeks + albumin and furosemide

1/3 have one episode

1/3 have infrequent relapses

1/3 have frequent relapses which stop before adulthood

Question 19

Focal segmental glomerulosclerosis

Answer 19

Can occur in adults and children

Most common GN seen on biopsy

Damage to podocytes occurs in focal (only some glomeruli), segmental (only some areas) regions

Recurs in 30-50% transplant patients

Biopsy: scarring of certain segments - can be missed if biopsy does not capture right area

Question 20

What is membranous nephropathy?

Answer 20

Causes nephrotic syndrome, accounts for 25% adult cases

Associated with lupus in younger women, hep B in children, cancer, drugs

IgG deposit between podocytes >> actiavte complement >> damages podocytes and mesangial cells

Diagnosis: anti-phospholipase A2 receptor antibody found in 80%, thickened GBM due complement deposition and spikes seen following silver stain

Question 21

What is membranoproliferative glomerulonephritis?

Answer 21

10% adult nephrotic syndrome

Type of glomerulonephritis caused by an abnormal immune response >> commonly presents as nephrotic syndrome OR nephritic syndrome

Immune complexes get stuck between podocytes

DIAGNOSIS: proliferative GN and electron dense deposits

Question 22

How does diabetes cause secondary nephrotic syndrome?

Answer 22

Secondary means occurring due to a systemic disease

Lots of glucose in blood: binds to proteins and the glucose+protein complex causes thickening of the basement membrane of the efferent arteriole meaning pressure builds up in the glomeruli as blood can’t leave

High pressure causes afferent to dilate which further icnreases pressure

In repsonse to high pressure and resulting high GFR, mesangial cells secrete factors which expands the size of the glomerulus

Causes formation of protein balls = Kimmel-Wilson nodules

Question 23

What is systemic amyloidosis?

Answer 23

Cause of secondary nephrotic syndrome

Amyloids - proteins with abnormal shape that stick together and get stuck in tissues

Amyyloidosis = result of tissue damage that occurs due to protein deposition

Often affect the kidneys

Congo red staining makes amyloids take on a pink colour

AA amyloidosis: caused by chronic inflammatory disease

AL amyloidosis: caused by haem malignancy

Question 24

Causes of nephrotic syndrome based on age

Answer 24

Children: minimal change = 75%, next is FSGS

Afults: 35% FSGS, 35% minimal change, 25% membranous nephropathy

Elderly: membranous nephropathy

Question 25

Investigations in nephrotic syndrome

Answer 25

FBC: poor kidney function = low EPO = low RBC

LFTs

CRP

Immunoglobulins

Complement levels

Coagulation profile - usually shows hypercoagulability because liver produces clotting factors in response to hypoalbuminaemia

Urinalysis: 24hr collection, protein; creatinine ratio

Imaging: USS

Biopsy to diagnose cause

Question 26

What is haemolytic uraemic syndrome?

Answer 26

Most common cause of AKI in children

Typically associated with E.coli infection >> shiga toxins circulate and bind to endotheial receptors in the kidneys, gut and brain

Causes vessel occlusion and damage to RBCs >> haemolytic anaemia

Classical presentation = profuse diarrhoea that turns bloody after 1-3 days >> admit to hospital

Investigations

E.Coli will be found in the stool of 80%

FBC: anaemia and thrombocytopenia

Urine: protein and blood

Management: purely supportive, fluids, anti-HTN, dialysis if needed