GN Flashcards
Features of glomerular haematuria:
Inflammation of glomerulus –>
- Haematuria: 80% red cells dysmorphic (phase contrast microscope)
- RBC casts (pathognomonic of glomerulonephritis) - light microscope
- Proteinuria
- Reduced renal function
Features of nephritic syndrome:
Inflammation of glomeruli.
Symptoms usually abrupt in onset:
P - Proteinuria (<3g/day) H - Hypertension A - Azotemia R - RBC casts / Haematuria O - Oliguria
Features of nephrotic syndrome:
= Proteinuria ≥3g/1.73m2/24hrs.
Secondary features:
- Hypoalbuminaemia
- Oedema
- Hyperlipidaemia (mixed hypercholesterolaemia / hypertriglyceridaemia)
+/- Hypertension
+/- Haematuria
+/- Renal impairment
How does the minimal change nephropathy come to be? What process?
There is some sort of T-cell dysfunction that leads to nephrotic syndrome. However the exact process is not known
but overall, what we see is:
Fusion of podocyte foot processes, seen on electron microscopy. Loss of charge selectivity of glomerular BM
Glomerulopathies with both low c3 and low c4?
Low C3 & C4:
SLE - diffuse
Membranoproliferative Type I
Cryoglobulinaemia
Glomerulopathies with low c3 but normal c4?
Low c3, normal c4:
SLE - diffuse Membranoproliferative Type II PSGN (post-infectious) Chronic infection Shunt nephritis HUS/TTP Cholesterol emboli
Pathological change in minimal change disease?
Fusion of podocyte foot processes, seen on electron microscopy. Loss of charge selectivity of glomerular BM.
Leads to nephrotic syndrome.
What is the most common cause of idiopathic nephrotic syndrome in children?
Minimal change disease.
Presents as nephrotic syndrome.
HTN, haematuria, renal impairment are uncommon.
May follow URTI.
Can be complicated by thrombosis, AKI or infections.
Treatment with steroids shortens the course of the illness.
Minimal change disease in adults:
- presentation?
- secondary causes?
M:F = 1
Nephrotic syndrome.
Compared with paediatric cases, greater prevalence of microscopic haematuria / HTN / renal impairment.
Majority are primary.
Secondary causes: neoplasia, drugs, infection, atopy, MC superimposed on another renal disease.
Treatment of minimal change disease (adults):
- High dose prednisone for initial treatment or for relapse.
Decrease dose when free of proteinuria (sustained).
- Steroid resistant: alkylating agents or cyclosporine.
FSGS vs MCN:
Minimal change nephropathy: fusion of podocyte foot processes.
FSGS: effacement (thinning/shortening) of foot processes.
Both present as nephrotic syndrome.
FSGS more likely to present with mild haematuria, HTN, impaired renal function.
Both can be steroid-responsive, but FSGS often slow / no response (except Tip Variant - overlap with MCN and usually steroid-responsive).
FSGS is progressive.
MCN usually completely resolves.
Primary Causes of FSGS:
Primary causes FSGS:
- Gene defects affecting glomerular apparatus: slit diaphragm proteins (nephrin, podocin, etc) and cytoskeletal proteins.
Hereditary conditions:
- Mitochondiral cytopathies (kidney disease + DM + hearing loss + muscle weakness or macular pattern dystrophy)
- WT1 mutation (Wilms Tumour suppressor gene) - regulates podocyte functions
Secondary Causes of FSGS:
Secondary Causes of FSGS:
- Hyperfiltration (shear stress on podocytes)
- Hypertensive Nephrosclerosis
- Viruses: HIV, parvovirus B19
- Drugs: heroin, lithium, pamidronate, interferon, sirolimus, calcineurin inhibitors
- Aging
Causative agents in post-infectious GN?
- Children: majority causes by streptococcal throat or skin infections.
- onset 1-3 weeks post pharyngitis
- 3-6 weeks post skin infection - Adults / elderly:
Strept appox. 30%
Staphylococcal infection more common cause
- latent period short than with strept
- site: skin > resp tract > UTI
- usually immunocompromised: T2DM, malignancy
Immunosuppressive therapy in PIGN?
No role for immunosuprressive therapy or plasmapheresis in PIGN.
Supportive therapy only
- control HTN
- electrolyte and fluid management
- RRT if indicated
HIVAN: briefly - - histology- treatment - prognosis
HIVAN: Collapsing FSGS on biopsy
Usually responds to HAART
Poor prognosis - often progresses to ESRF
Adjuvant therapies in nephrotic syndrome:
- control BP <20)
[loss of protein C, S and AT-III)
What are the main types of cells in the glomerulus?
There is the filtration unit, and then the supportive structures.
Filtration unit:
- podocytes
- basement membrane
- endothelial cells
Supportive:
- mesangial
- stroma etc
What are some common ways to classify glomerular disease?
Firstly we can use aetiology:
- primary - known histology with unknown cause
- associated with specifics primary disorder
Secondly we can use histology:
- non-proliferative - this is a glomerulopathy but not inflammation
- proliferative - this is the GNs. There is inflammation with demonstrable cellular proliferation (can be endothelial, mesangial or epithelial [podocyte])
What are the indications of renal biopsy?
for diagnostics:
- nephrotic syndrome
- nephritic syndrome
- RPGN
- asymptomatic haematuria AND proteinuria/renal impairment
- unexplained AKI
Isolated asymptomatic haematuria is not an indication
For prognostics:
- to determine the degree of active v chronic disease
- interstitial fibrosis is a major predictor of outcome in chronic GN
How do we treat FSGS?
In secondary causes, it is important to treat the underlying cause
A good idea is to reduce the intraglomerular pressure and also reduce proteinuria.
- this is achieved by RAAS blockade –> leads to decreased level of TGF-beta (transforming growth factor); decreased dilation of efferent arteriole
What are some prognostic features of FSGS?
subnephrotic range proteinuria is a GOOD thing - treat with ACEi and avoid immunosuppression
High proteinuria +/- poor renal function +/- tubulointerstitial injury is POOR prognostics
- treat these with steroids.
- if non-responsive –> cyclosporine
if patients respond to therapy, then they have a 90% 10 year renal survival
What is the most common cause of nephrotic syndrome in the 60 year old male?
Membranous nephropathy - DO NOT BE FOOLED BY THE STATEMENT THAT FSGS IS THE MOST COMMON AT RBWH - THIS ONLY REFERS TO THEIR BIOPSY PROVEN AT RBWH
What are the causes of membranous nephropathy?
Primary (idiopathic) make up 80% of all causes
Secondary:
- drugs - gold, penicillamine after 12 months, NSAIDs
- CA - lung, colon, stomach, breast, kidney, prostate
- Infection - HBV, HCV, syphilis, EBV
- Immunological - SLE, MCTD
