Glomerulonephritis Flashcards
what is glomerulonephritis?
immune-mediated diseases of the kidney affecting the glomeruli (characteristically by inflammation)
usually affecting both kidneys
usually occurs several weeks after an infection (secondary to tubulointerstitial damage)
what part of the immune system is involved in glomerulonephritis?
humoral - antibody
- intrinsic/ planted antigen
- deposition of circulating immune complexes
T-cell mediated
inflammatory cells, mediators and complements
who gets it?
Primary = idiopathic (majority)
Secondary
- infections
- drugs
- associated malignancies
- part of systemic disease: ANCA +ve, vasculititis SLE, GPA, HSP
How are glomerulonephritis’s classified?
By aetiology - primary/secondary histology - proliferative/non-proliferative - focal (<50%)/ diffuse (>50%) - global (all of glomeruli)/segmental (part of glomeruli) - cresentic - RPGN
how does glomerulonephritis present?
haematuria - painless proteinuria impaired renal function hypertension nephrotic syndrome nephritic syndrome
what is haematuria in glomerulonephritis?
Aysymptomatic microscopic haematuria
Episodes of painless macroscopic haematuria
urine microscopy
- dysmorphic RBCs (squished)
- red cell cast (=endothelial injury)
how is it diagnosed?
Clinical presentation Blood test (ANA, ANCA, anti-GBM testing) Kidney biopsy (1:400 risk of bleed) Examination of urine - urinalysis - proteinuria/ haematuria - Urine microscopy - RBC (dysmorphic), RBC casts, lipiduria -Urine protein - creatinine ratio/24hr
histological findings of biopsy?
light microscopy
- hypercellularity - inflammatory cells and reactive proliferations
- sclerosis
- crescents - this is bad
electron microscopy (see where the deposits are, can look at BM)
- subepithelial
- mesangial
- subendothelial
immunofluorescence (what antibody and distribution - IgM, IgA, IgG)
- IgG - Goodpasture’s
what is the aim of glomerulonephritis treatment?
decrease proteinuria
remission of nephrotic syndrome
longterm renal function
what are the immunosuppressive treatments?
corticosteroids (prednisolone PO, methylpredisolone IV)
azathioprine
alkylating agents (cyclophosphamide, chlorambucil)
calcineurin inhibitors
mycophenolate mofotil
plasmapheresis
antibodies - IV immunoglobulin, monoclonal T/B antibodies
Goodpastures - cyclophophamide (azathioprine/ MMF maintenance)
what are the non-immunosuppressive treatments?
anti-HTN (target<130/80 if proteinuria <120/75) ACEi/ARBs diuretics statins anticoagulants/aspirin/antiplatelets dialysis transplant
how to treat nephrotic patients?
Aim is sustained remission - complete proteinuria <300mg/day and partial proteinuria <3g/day fluid restriction salt restriction diuretics ACEi/ARBs anticoagulation? IV albumin - if V deplete immunosuppression
what is minimal change nephropathy?
normal renal biopsy on light microscopy
foot process fusion on electron microscopy (podocytes)
who gets minimal change nephropathy?
commonest cause of nephrotic syndrome in children
possibly caused by IL-3
what 3 factors are highly suggestive of minimal change neuropathy?
response to steroids/immunosuppressives
occurs with Hodgkin’s lymphoma with remission following successful treatment
patients and family have increased incidence of asthma and eczema (remission of the nephrotic syndrome following antigen avoidance)
how is minimal change nephropathy treated?
oral steroids - 94% complete remission
if steroid resistant/dependent/multiple relapses - cyclophosphamide/CSA
what is membranous nephropathy?
sub epithelial immune complex deposition in the basement membrane - the basement is thicker and the electron dense deposits create a ‘spike and dome’ appearance
what is the pathogenesis in membranous nephropathy?
anti-PLA2r antibody id seen in 70%, PLA2r is an antigen on podocytes
Thickened BM - silver staining
who gets membranous nephropathy?
2nd most common cause of nephrotic syndrome in adults
primary - idiopathic
secondary
- associated with infections (Hep B, parasites)
- connective tissue diseases (SLE)
- malignancy (carcinoma, lymphoma)
- drugs (gold, penicillin)
what is the prognosis of membranous nephropathy?
30% develop ESRT after 10 years
how is membranous nephropathy managed?
steroids
alkylating agents
B cell monoclonal antibody
What is focal segmental glomerulosclerosis?
focal <50% of the tissue segmental part of the glomeruli focal segmental GS on LM minimal Ig/complement deposition because segmental can be missed on biopsys
who gets focal segmental glomerulosclerosis?
commonest cause of nephrotic syndrome in adults primary - idiopathic secondary - HIV - heroin - obesity - reflux
what is the prognosis of focal segmental glomerulosclerosis?
50% develop ESRF after 10 years
what is the management of focal segmental glomerulosclerosis?
prolonged steroids
remission in 60%
how does it present?
massive proteinuria
haematuria
hypertension
renal impairment
What is membranoproliferative nephropathy?
big lobulated hypercellular glomeruli with thick membranes - tram tracks (duplication of BM)
who gets membranoproliferative nephropathy?
idiopathic
type 2 - infection, lupus, malignancy
adults and children
how does membranoproliferative nephropathy present?
nephritic/nephrotic syndrome - can be either
what is the prognosis of membranoproliferative nephropathy?
is dependent on the severity
what is IgA nephropathy?
mesiangial cell proliferation and expansion on LM and IgA deposits in the mesangium on immunofluorescence
- follows a resp/GI infection by a couple of days
who gets IgA nephropathy?
commonest glomerulonephritis associated with HSP - arthritis - colitis - purpuric rash
how does IgA nephropathy present?
asymptomatic microhaematuria +/- non-nephrotic proteinuria
macroscopic haematuria after a couple of days resp/GI infection (haematuria a couple of WEEKS after an infection is post-infective nephropathy)
AKI/CKD
what is the prognosis of IgA nephropathy?
25% develop ESRF after 10 yrs
how is IgA nephropathy managed?
BP control
ACEi/ARB
fish oil
what is rapidly progressive glomerulonephritis?
a treatable cause of AKI
it has a systemic association
how does rapidly progressive glomerulonephritis present?
treatable cause of acute renal failure
rapid deterioration in renal function over days/weeks
active urinary sediment - RBC, RBC and granular cast
part of systemic disease
glomerular crest on biopsy
who gets rapidly progressive glomerulonephritis?
ANCA+ve - GPA (cANCA, PR3) - MPA (pANCA, MPO) - wegners granulomatosis - Churg-Strauss syndromes ANCA -ve - Goodpasture's (antiGBM, IgG) - HSP/IgA, - SLE
how is rapidly progressive glomerulonephritis managed?
systemic and renal management is needed
immunosuppression
- steroids: PO prednisolone, IV methylprednisolone
- cytotoxics: cyclophosphamide, mycophenolate, azathioprine
supportive treatment (dialysis)
plasmapheresis
what is diabetic nephropathy?
kidneys initially enlarge and there is hyperfiltration (GFR >150mL/min)
pathology in diabetic nephropathy?
diffuse and nodular glomerulosclerosis
Kimmel Stiel Wilson lesion - nodules
thickening of glomerular basement membrane and mesangial expansion
also microvascular disease - arterial sclerosis
how is diabetic nephropathy managed?
lifestyle advice
ACEi/ARB regardless of BP
linear IgG glomerularnephritis?
Goodpasture’s Syndrome
difference between glomerulonephritis and glomerulopathy?
if there is predominant inflammation on histology then glomerular disease can be glomerulonephritis
if inflammation is absent - an awful lot of overlap and they are sometimes used interchangeably but this isn’t correct
what cells are more involved in nephrotic syndrome?
pOdocytes
- proteinuria
- oedema
- hyperlipidaemia
what cells are more involved in nephritic?
endothelial and mesangial cells
- haematuria
- hypertension
What is nephritis?
Generic term that means inflammatory of kidneys, not a diagnosis or syndrome with criteria
What is nephritic syndrome/acute nephritis syndrome?
Haematuria
Oliguria
Proteinuria
Fluid retention
What is oliguria?
Significantly reduced urine output
What is nephrotic syndrome?
Refers to group of symptoms without specifying underlying cause
-Not a disease, a way of explaining symptoms
Criteria:
- Peripheral oedema
- Proteinuria
- Serum albumin
- Hypercholesterolaemia
Types of glomerular nephritis?
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
- IgA nephropathy
- Post-streptococcal glomerulonephritis
- Mesangiocapillary glomerulonephritis
- Rapidly progressive glomerulonephritis
- Good pasture syndrome
What is IgA nephropathy AKA?
Mesangioproliferative glomerulonephritis
What are most types of glomerulonephritis treated with?
Immunosuppression (roids)
BP control with ACEis/ARBs
Presentation of nephrotic syndrome?
Usually oedema
Possible frothy urine
Predisposes patients to thrombosis, HT, and high cholesterol
Most common cause of primary glomerulonephritis?
IgA nephropathy
Most common type of glomerulonephritis overall?
Membranous glomerulonephritis
what are the nephrotic syndrome triad?
proteinuria >3g/day
hypoabuminaemia <30g
oedema (hypercholesterolaemia)
what syndrome is often seen with normal renal function?
nephrotic syndrome complications - infection - RV thrombosis - PE
what are the signs and symptoms of nephritic syndrome?
AKI oliguria oedema/fluid retention - not to the degree of nephrotic hypertension active urinary sediment - RBC - granular cast - proteinuria
