glomelOnef Flashcards
what is gn
immune-mediated disease of the kidneys affecting the glomeruli (w/ secondary tubulointerstitial damage)
pathogenesis of gn
humoral (antibody-mediated)
- intrinsic or planted antigen
- deposition of circulating immune complexes
cell-mediated (t-cells)
inflammatory cells, mediators and complements
significance of glom cap wall
size and charge selective barrier
(in gn - disruption of barrier leads to haematuria and/or proteinuria)
damage to endothelial or mesangial cells leads to…
a proliferative lesion and red cells in urine
damage to podocytes leads to…
a non-proliferative lesion and protein in urine
**cells of nephron respond to injury in different ways
diagnosing gn through ____
clinical presentation
blood tests
examination of urine
kidney biopsy
specific exams of urine for rn
urinalysis - haematuria
urine microscopy - rbc (dysmorphic), rbc & granular casts, lipiduria
urine protein - creatinine ratio/24hr urine - quantify proteinuria
clinical renal presentations
haematuria (red cells in urine)
- asymptomatic microscopic haematuria
- episodes of painless macroscopic haematuria
proteinuria/albuminuria
microalbuminuria (30-300mg albuminuria/day)
asymptomatic proteinuria (<1 g/day)
heavy proteinuria (1-3 g/day)
nephrotic syndrome (> 3 g/day))
what do rbcs look like in gn
dysmoprphic (squishy squashy squashed squashers)
NEPHR(iiiiiiiii)tic syndrome
acute decline in kidney function
oliguria
oedema caused by fluid retention
hypertension
“active” urinary sediment (RBCs, RBC casts)
indicative of a proliferative process
affecting endothelial cells
NEPHR(ooooooo)tic syndrome
proteinuria > 3 g/day (mostly albumin, also globulins)
hypoalbuminaemia (<30)
oedema
hypercholesterolaemia
usually normal renal function
indicative of a non proliferative process
affecting Podocytes
nephr(OOOO)tic syndrome
infections - loss of opsonising antibodies
renal vein thrombosis
pulmonary emboli
volume depletion (overaggressive use of diuretics) - may lead to AKI (pre-renal)
vit D deficiency
subclinical hypothyroidism
classifications
- AETIOLOGY
- (majority)
- caused by eg. infections or drugs associated with eg. malignancies or part of systemic disease eg. ANCA - associated systemic vasculitis, lupus, Goodpastures, HSP - HISTOLOGY
renal biopsy
(light microscopy/immunofluorescence/EM)
histological classification in GN terminology
- proliferative or non-proliferative (usually refers to presence or absence of proliferation of mesangial cells)
- focal/diffuse (< or > 50% glomeruli affected)
- global/segmental (all or part glomerulus affected)
- crescentic (presence of crescents - extracapillary proliferation of inflammatory cells within Bowman’s space, eg RPGN in vasculitis)
treatment of GN principles
reduce degree of proteinuria
induce remission of nephrotic syndrome
preserve longterm renal function
non immunosuppressive treatments of gn
- anti-hypertensives (target BP <130/80 if proteinuria)
- ACE inhibitors/ ARBs
- SGLT2i
- diuretics
- statins
- anticoagulants in nephrotic syndrome with profound hypoalbuminaemia
immunsuppression treatments
DRUGS
- corticosteroids (Prednisolone po/MethylPred IV)
- alkylating agents (Cyclophosphamide/ Chlorambucil)
- calcineurin inhibitors (Cyclosporin/Tacrolimus)
- anti-proliferatives (azathioprine/MMF)
PLASMAPHERESIS
- (TPE-therapeutic plasma exchange)
ANTIBODIES
-IV Immunoglobulin (IVIG)
-Monoclonal Antibodies
treatment of nephr(OOOOO)tic patients
GENERAL
- fluid restriction (less than 1.5l in a day)
- salt restriction
- diuretics
- ACE Inhibitors/ ARBs
- consider Anticoagulation if albumin<20
- IV Albumin (only if volume deplete) statins to try increase oncotic pressure that is in wrong place
how many treatment nephrOOOOtic involves immunosuppression?
MOST
aim is to induce sustained remission
- complete remission (proteinuria < 300mg/day)
- partial remission (proteinuria <3g/day)
idiopathic GN main types
minimal change
fsgs
membranous
membranoproliferative
igA nephropathy
rapidly progressive glomerulonephritis
minimal change nephropathy
- commonest cause of nephrotic syndrome in children (77%)
- normal renal biopsy on LM & IF with foot process fusion on EM.
- 94 % complete remission with oral steroids
- some are steroid-resistant/ dependent or have multiple relapses
- second-line drugs: cyclophosphamide/CSA
- does NOT cause progressive renal failure
- possibly caused by IL-13, anti-nephrin Ab
fsgs
- commonest cause of nephrotic syndrome in adults (35%)
- (HIV/Heroin use/Obesity/ Reflux nephropathy) or genetic
- renal biopsy: As its name describes on light microscopy with minimal Ig/ Complement deposition on IF
- remission with prolonged steroids in 60 %
- 50 % progress to end stage renal failure after 10 years
membranous nephropathy
- 2nd commonest cause of nephrotic syndrome in adults (15-30%)
- 1 or 2
- important 2 causes include: infections (hepatitis B/ parasites), connective tissue diseases (lupus), malignancies (carcinomas/ lymphoma), drugs (gold/penicillamine)
- renal biopsy: subepithelial immune complex deposition in the basement membrane
- steroids/ Alkylating agents/B cell monoclonal Ab
- 30% progress to end stage renal failure in 10 years
anti PLA2r antibody
present in >70% of primary MN
histological appearance of membranous nephropathy
thickened basement membranes - silver stain
more membranprolif glomeruloneph
membranoproliferative gn
- pattern of injury with different causes.
- 2 primary mechanisms;
- immune complex deposition and complement activation.
- dysregulation of the alternative complement pathway.
igA nephropathy
- commonest GN in the world
- asymptomatic microhaematuria +- non-nephrotic range proteinuria
- macroscopic haematuria after resp/GI infection
- AKI/ CKD
- associated with Henoch-Schonlein Purpura (HSP) (arthritis/colitis/ purpuric skin rash)
- renal biopsy: Mesangial cell proliferation and expansion on light microscopy with IgA deposits in mesangium on IF
- 25% progress to end stage renal failure in 10-30 years
- BP control/ ACE inhibitors & ARBs/ Fish oil
immunology
process diagram
iga nephropathy
mesangial cell proliferation and expansion (H&E stain)
rpgn
- treatable, immune mediated cause of acute kidney injury
- rapid deterioration in function over days/weeks
- ‘active’ urinary sediment (RBCs, RBC & Granular Casts)
- may be part of systemic disease.
- associated with glomerular crescents on biopsy.
hsitologiacl buzzword
crescent formation
rpgn treatment
treatement
