Glomerulonephritis Flashcards
What is glomerulonephritis?
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)
OK so what do the terms nephrotic and nephritic refer to…?
The terms nephrotic and nephritic are used to group types of glomerulonephritis by their clinical syndrome/ presentation
THEY ARE NOT DISEASES IN THEMSELVES
What is nephritic syndrome?
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
Types of nephritic syndrome
- IgA nephropathy = most common type in the world
- Henoch-Schönlein purpura
- Post-strep/ post infectious glomerulonephritis
- Godpasture’s/ anti glomerular basement membrane disease
- Rapidly progressive glomerulonephritis
What is IgA nephropathy?
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
5 year old has palpable purpuric rash, abdominal pain, kidney involvement and joint pain – thoughts?
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
Why are ARBs/ ACEi used to treat IgA nephropathy?
Many cases progress to ESRD and cause HTN so important to control BP to prevent further damage to kidney and reduce protein
Classical presentation of post-strep GN?
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
What is Goodpasture’s disease? AKA anti-glomerular basement membrane disease
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
What can cause rapidly progressive glomerulonephritis?
Goodpasture’s, vasculitis, lupus
Histology: crescentic glomerulonephritis is classical finding
Allport syndrome
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
What is nephrotic syndrome
Triad of:
- Loss of >3g protein in the wee over 24hrs
- Loss albumin in blood <30g/L
- Oedema
Pathophysiology of nephrotic syndrome?
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
There are causes of primary nephrotic syndrome - what are they?
- Minimal change - children are mini
- Focal segmental - adults and kids, segment from both ages
- Membranous glomerulopathy - common in adults
What might be the only indication a patient has nephrotic syndrome?
Pitting oedema and frothy urine (due to proteins)
How is nephrotic syndrome managed?
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
Complications of nephrotic syndrome
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
Child has nephrotic syndrome, most common cause?
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
Focal segmental glomerulosclerosis
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
What is membranous nephropathy?
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
What is membranoproliferative glomerulonephritis?
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
How does diabetes cause secondary nephrotic syndrome?
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
What is systemic amyloidosis?
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
Causes of nephrotic syndrome based on age
Children: minimal change = 75%, next is FSGS
Afults: 35% FSGS, 35% minimal change, 25% membranous nephropathy
Elderly: membranous nephropathy
Investigations in nephrotic syndrome
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
What is haemolytic uraemic syndrome?
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
