glomerular disorders Flashcards
what layers are the glomerular filtration barrier made of?
endothelium (of the blood vessels)
glomerular basement membrane
podocytes (epithelium)
what do the mesangial cells do?
maintain the structure of the glomerulus
what is a crescent?
an aggregate of macrophages and epithelial cells in Bowman’s space
what are the different presentations of glomerulonephropathy/ glomerulonephritis? NB these are examples of different presentations not all features are present at the same time
asymptomatic nephrotic syndrome nephritic syndrome rapidly progressing GN macroscopic haematuria chronic GN urine dipstick shows blood and protein in it
what is the triad of nephritic syndrome?
abnormal kidney function
blood and protein ion the urine dipstick
HYPERtension
what are the features of nephrotic syndrome?
- nephrotic range proteinuria where you leak >3g of protein in the urine
- oedema
- low albumin in the blood ie hypoalbuminaemia
- hyperlipidaemia
- may or may not be hypertensive
- kidney function may or may not be abnormal
what is the time over which rapidly progressing GN develops?
2-3 weeks
How does a person with chronic GN present?
with all the stages of CKD
- abnormal kidney function
- anaemic
- bone disease
- blood and protein in the urine dip
- HYPERtension and this progresses over months or years
which is more aggressive, nephrotic or nephritic syndrome?
nephritic due to the hypertension and the abnormal kidney function
what must you see on the urine dipstick to diagnose GN?
blood and protein
what antibody would we be looking for if we suspect vasculitis?
ANCA
what are the small vessel vasculitides affecting the kidney?
granulomatosis with polyangitis (GPA)
microscopic polyangitis (MPA)
renal limited vasculitis - without systemic features
eosinophilic granulomatosis
what are some extra-renal signs associated with ANCA positive vasculitides?
sinusitis epistaxis lung involvement = haemoptysis GI affected - eg PR bleeding skin rash
also constitutional symptoms:
- lethargy
- weakness
- weight loss
which vessels does small vessel vasculitis involve?
capillaries
venules
arterioles
small arteries
How are the subtypes of vasculitis diagnosed?
through the accompanying signs of the vasculitis eg whether other organs are involved etc
what are the investigations that are done for vasculitis?
URINE DIPSTIK
ANCA ie immunology screen
renal biopsy
what is seen on renal biopsy in vasculitis?
- segmental glomerular necrosis
- crescent formation
- fibrosis
- tubular atrophy
when can you get a false positive with ANCA?
in paraneoplastic syndromes
How is vasculitis treated?
induction with steroids and cyclophosphamide and then maintenance immunosuppression with azathioprine
if they have RPGN, treat with plasma exchange
which type of ANCA is found in the majority of cases of Granulomatosis with polyangiitis (GPA)?
c-ANCA ie t he cytoplasmic PR3 ANCA
which which type of ANCA is there more extra-renal manifestations, higher mortality and higher relapse rate?
c-ANCA
what is the gold standard for diagnosis of IgA nephropathy?
renal biopsy - will see IgA deposits eg in mesangium (as well as subendothelial and epithelial)
What is the pathophysiology of IgA nephropathy?
a pt has a mucosal infection eg a cold and produces abnormal IgA that gets trapped in the glomerulus
or due to exaggerated bone marrow IgA immune response to viral or other antigens these deposits induce mesangial cells activation and proliferation
where are the deposits of IgA in the glomerulus?
mesangium
filtration membrane
subendothelial
subepithelial
what is the parietal epithelium of the glomerulus called?
Bowman’s capsule
What is the visceral epithelium of the glomerulus composed of?
podocytes
what is the most prevalent glomerular disease?
IgA nephropathy
Does IgA nephropathy have any extra-renal features and if not what is it called when it does?
IgA nephropathy is limited to the kidneys and it is called Henoch–Schönlein purpura if it is not
what type of individuals commonly get IgA nepohropathy?
young males eg in case it was 17yrs
what is the commonest condition to be found incidentally with asymptomatic blood and protein in the urine?
IgA nephropathy
How does IgA nephropathy present?
Can present asymptomatically
or visible haematuria with mucosal infection
nephrotic syndrome may occur in 5%
what are two possible reasons for people with IgA nephropathy to present with AKI?
acute tubular necrosis
or crescentic GN
How is IgA nephropathy treated?
If it is crescentic on biopsy, then it is treated like vasculitis ie with steroids and cyclophosphamide but if it is non-crescentic, then the treatment is supportive with fluids and the protein leak is reduced by giving ACE-Is or ARBs, good BP control, weight management, healthy lifestyle
Which popln of people is Lupus more common in?
African Americans, Afro-carribeans, Hispanics and Asians
female
15-45 yrs old
what antibodies may you see in a pt with Lupus nephritis?
ANA
Anti-dsDNA
describe the classification system for Lupus nephritis
Class 1 - normal glomeruli in light microscopy but mesangial immune deposits on IF class 2 - mesangial hypercellularity with mesangial immune deposists class 3 - FOCAL segmental proliferative class 4 - diffuse proliferative so from class 2-4 more mesangial cells and more deposits in the filtration membrane, sub endothelial and mesangial deposits class 5- membranous lupus = deposits in the subepithelium so the problem is moving outwards from the glomerulus class 6 - advanced sclerosing = damage has been going on for some time and there is healing and scarring
how is Lupus nephritis treated?
induction and maintenance with immunosuppression ie cyclophsophamide and steroids
supportive care as there is risk of progressing with proteinuria ie BP control, diet. lower cholesterol
in which syndrome would you need to give anticoagulants?
nephrotic syndrome - as losing a lot of protein and therefore anti-coagulants in the urine
what are the consequences of nephrotic syndrome (not the features of it)?
hypercoagulability
loss of binding proteins leading to drug dose adjustments
risk of infections due of loss of Igs
what is the pathophysiology of membranous glomerulonephropathy?
autoimmune
thickening of endothelium
IgG and complement deposits in the subepithelial layer
what age group does membranous GN affect?
middle age people
what is the pathophysiology of membranous GN?
Abs develop against the phospholipase A2 receptor antigen
what conditions can lead to secondary membranous GN?
autoimmune conditions
viruses eg Hep b, c
drugs eg NSAIDs
tumours
how does membranous GN present?
nephrotic syndrome
how is membranous GN diagnosed?
serum PLA2R Ab
renal biopsy
what is the gold standard test for membranous GN?
renal biopsy
what is the management of membranous GN?
- many pts will undergo spontaneous remission
- supportive treatment - control of oedema, hypertension, hyperlipidaemia, proteinuria by ACEIs/ARBs, diet and lifestyle and anti-coagulation if the albumin is very low
- immunosuppression with cyclophosphamide
- treat the underlying cause and the membranous nephropathy should resolve
what pt population normally suffers from minimal change disease?
children
how does minimal change disease present?
nephrotic syndrome
how is minimal change disease diagnosed?
biopsy
what is the natural history of minimal change disease?
relapsing and remitting
does minimal change disease progress to renal failure?
no
How is FSGS distinguished from minimal change disease?
FSGS tend to have progressive renal failure but in MCD there is no renal failure
what is the pathophysiology of minimal change disease?
podocytes are defaced which means that proteins can leak from the glomerulus
would you do renal biopsy for minimal change disease?
no as the pts are usually children and biopsy is quite invasive = instead give them steroids and if they respond then they have minimal change
what would be seen on biopsy for minimal change disease?
normal glomeruli under light microscope
under EM would see podocyte defacement
would not see any Ig deposits
What causes minimal change?
many drugs can cause it: - NSAIDs - lithium - antibiotics - bisphosphonates - sulfasalazine can be triggered by allergic reactions infections eg hep C, HIV and TB
what is the treatment for minimal change disease?
very responsive to steroids eg prednisolone
use cyclophosphamide
what is the pathophysiology of FSGS?
primary FSGS is due to an unknown permeability factor increases permeability of glomeruli so there is increased protein leak, may be an autoimmune disease or can be part of lupus
secondary FSGS is due to number of functioning nephrons are reduced for any reason
haemodynamic glomerular strain leads to sclerosis
as nephrons fail, increased flow through the remaining nephrons leads to hydraulic injury
this is HYPERFILTRATION
what are the causes of secondary FSGS?
reduced nephron number:
- nephrectomy
- hypertension
- gross obesity
- ischaemia
- IgA nephropathy
mutations in the podocyte genes
viruses - HIV, CMV, EBV
drugs eg NSAIDs
how does FSGS present?
massive proteinuria, haematuria
hypertension
renal impairment
often resistant to steroids
what is seen on biopsy with FSGS?
segmental glomerulosclerosis seen on light microscopy, this progresses to global sclerosis
foot process effacement
What are the nephrotic conditions ie conditions that result in nephrotic syndrome?
minimal change nephropathy focal segmental glomerulosclerosis amyloidosis membranous glomerulonephropathy diabetic nephropathy
what are the nephritic conditions?
Lupus nephritis
HSP - Henoch-Schönlein syndrome (IgA nephropathy with extra-renal manifestations)
Membranoproliferative GN
