Glomerulonephritis Flashcards
what makes up the renal parenchyma
tubules, interstitium, glomeruli
what type of disease is glomerulonephritis
glomerular disease
what are the two types of glomerulonephritis
chronic- 2nd commonest cause of end stage renal failure
acute- important treatable cause of acute renal failure
what is glomerulonephritis
range of immune mediated diseases of the kidneys affecting the glomeruli (with secondary tubulointerstitial damage)
what is the difference between primary and secondary glomerulonephritis
primary= no associated disease (majority idiopathic) secondary= glomerular involvement is part of systemic disease (e.g. SLE, infections, drugs, malignancies, ANCA, goodpastures, HSP)
what does damage to endothelial or mesangial cells cause
a proliferative lesion
- red cells in urine
- aggressive nephritic picture
- influx of inflammatory cells
what does damage to podocytes cause
a non proliferative lesion
- protein in urine
- dont get dramatic inflammatory response
- loose ability to retain albumin
what happens when there is podocyte damage
it atrophies
loss of specific barrier function
proteinuria
what happens when there is mesangium damage
proliferative response
release of Ang.2, chemokines
attract inflammatory cells
what causes damage to the glomerular endothelium
vasculitis
what tests to diagnose GN
blood tests urinalysis urine microscopy- RBC (dysmorphic), RBC & granular casts, lipiduria urine protein: creatinine ratio kidney biopsy
what types of haematuria will renal presentation cause
asymptomatic microscopic
episodes of painless haematuria (wont produce painful haematuria)
what are the parameters of proteinuria
Microalbuminuria (30-300mg albuminuria/day) Asymptomatic proteinuria (< 1 g/day) Heavy proteinuria (1-3 g/day) Nephrotic syndrome (> 3 g/day))
do you do a kidney biopsy for everyone
no as risk of bleeding
what are red cell casts Pathognomonic of
GN with injury to mesangium
what are the clinical presentations of GN
impaired renal fucntion (AKI, CKD/ ESRD)
hypertension
nephritic/nephrotic syndrome
nephritic-nephrotic syndrome
what is nephritic syndrome
- acute renal failure
- oliguria
- oedema/ fluid retention (caused by reduce urine output)
- hypertension
- active urinary sediment (RBC’s, granular casts)
what is nephritic syndrome indicative of
proliferative process
affecting endothelial cells
what is nephrotic syndrome
- proteinuria >3g/day
- hypoalbuminaemia
- oedema
- hypercholesterolaemia (live working overtime)
- usually normal renal function (normal creatinine and BP)
what is nephrotic syndrome indicative of
a non proliferative process affecting podocytes
what are the possible complications of nephrotic syndrome
infection (loss of opsonising antibodies)
renal vein thrombosis
PE (increased DVT risk)
volume depletion (overaggressive use of diuretics may lead to ARF)
vit d def
subclinical hypothyroidism
How does the presentation of GN differ from a non glomerular disease like Interstitial Nephritis?
In glomerular disease can have blood or protein in urine
In a interstitial nephritis- should not have blood or protein or urine
how do you classify GN
aetiology (primary or secondary)
histology (renal biopsy, light microscopy, immunofluorescence, EM)
what are the histological classifications of GN
proliferative vs non proliferative (proliferation of mesangial cells)
focal/ diffuse (< or > 50% glomeruli affected)
global/ segmental (all or part of glomerulus affected)
crescentic (presence of cresents- epithelial cell extracapillary proliferation- e.g. RPGN in vasculitis)
what are the principles of GN treatment
reduce degree of proteinuria
induce remission of nephrotic syndrome
preserve longterm renal function
what are the non immunosuppressive treatments for GN
Anti-hypertensives (target BP <130/80 - <120/75 if proteinuria) ACE inhibitors/ ARBs Diuretics Statins (hypercholesterolaemia) ? Anticoagulants/ Aspirin/ Antiplatelets ? Omega 3 fatty acids/ Fish oil
what are the immunosuppression therapies for GN
Drugs
Corticosteroids (Prednisolone po/MethylPred IV)
Azathioprine
Alkylating agents (Cyclophosphamide/ Chlorambucil)
Calcineurin inhibitors (Cyclosporin/Tacrolimus)
Mycophenolate Mofetil (MMF)
Plasmapharesis (TPE-therapeutic plasma exchange)
Antibodies:IV Immunoglobulin
Monoclonal T or B cell Antibodies
what is the general treatment for nephrotic patients
Fluid restriction Salt restriction Diuretics ACE Inhibitors/ ARBs ? Anticoagulation IV Albumin (only if volume deplete)
IMMUNOSUPPRESSION
what is the aim of treatment for nephrotic patients
to induce sustained remission: complete remission (proteinuria < 300 mg/day) partial remission (proteinuria < 3g/day)
what are the types of non proliferative GN
minimal change GN
focal segmental glomerulosclerosis
membrane GN
describe minimal change GN
damage to podocytes
commonest cause of nephrotic syndrome in children
seen on EM
94% complete remission with oral steroids
doesnt cause progressive renal failure
describe focal segmental glomerulosclerosis
commonest cause of nephrotic syndrome in adults
primary/ secondary to HIV/herion/obesity/reflux/ nephropathy
segements of glomeruli develop sclerosis
60% response to steroids
50% progress to ESRF
describe membranous nephropathy
2nd commonest cause of nephrotic syndrome in adults
primary/ secondary (hep b, parasites, CTD- lupus, malignancies, drugs (gold, pencillamine))
renal biopsy- immune complex deposition in BM
thickened glomerular BM
steroids/ alkylating agents/ B cell monoclonal Ab
1/3rd progress to ESRD
1/3rd go into remission
anti PLA2r antibody
what are the types of proliferative GN
IgA nephropathy
rapdily progressive GN
membranoproliferative GN
post infectious GN
describe IgA nephropathy
most common GN in adults
proliferative
macroscopic haematuria after resp/GI infection
AKI/CKD
associated with HSP (arthritis, colitis, purpuris skin rash)
renal biopsy- IgA deposits, proliferation
5% ESRF in 10 years
BP control, ACRi, ARBs, fish oil
describe rapidly progressing GN
cresenteric (glomerular cresents on biopsy)
either ANCA positive or ANCA negative
treatable cause of AKF
rapid deterioration in renal function over weeks/ days
RBCs and granular casts in urine
what are the ANCA positive RPGN
GPA (vasculitis affecting lungs, kidneys, ect. c-ANCA positive, treat with steroids + cyclophosphamide)
MPA (small vessel vasculitis, p-ANCA +ve, tx with long term steroids)
what are the ANCA negative RPGN
Goodpasture’s disease-Anti-GBM
Henoch Scholein Purpura HSP/IgA
Systemic Lupus Erythematosus SLE
what is the tx for RPGN
AIM IS TO CONTROL THE SYSTEMIC AS WELL AS RENAL DISEASE
Immunosuppression
Steroids (IV Methylprednisolone / Oral Prednisolone)
Cytotoxics (Cyclophosphamide/ Mycophenolate/ Azathioprine
Plasmapharesis
what is membraneprolifrative GN
primary/ secondary (SLE, hep)
usually progresses to ESRF
describe post infectious GN
occurs weeks after URTI (usually strep pyogenes)
supportive Tx
resolves in 2-4 weeks
describe IgA nephropathy
most common GN in adults
proliferative
macroscopic haematuria after resp/GI infection
AKI/CKD
associated with HSP (arthritis, colitis, purpuris skin rash)
renal biopsy- IgA deposits, proliferation
5% ESRF in 10 years
BP control, ACRi, ARBs, fish oil
