GN Flashcards
PAN - Polyathritis nodosa
Small micro aneurysms, looks like beads.
Affects medium sized vessels
Associated with Hepatitis B
Symptoms - systemic. Livedo reticulariis, gut - abdo pain and bloody stools, Renal Ischemia, raised BP
Tx = steroids, cyclophosphamide
Features of primary Vs secondary FSGS
Primary - true nephrotic syndrome, low albumin, raised UPCR - associated with APOL 1 - Gene
also see podocyte effacement
Secondary - Albumin maintained and UPCR not as high - associated with Infection - HIV, Drugs - Lithium, etc
FSGS - What circulatory factor is associated
Circulating glomerular permeability factor
3 x organised deposits
Firbillary
Immunotactoid
Amyloid
Non organized deposits
Monoclonal immunoglobulin deposition disease -
-Light chain more commonly associated with Kappa
- Heavy chain more commonly associated with Lambda - or AL amyloid
What is the commenest type of myeloma
IgG myeloma (70%) and IgA meyloma (30%)
AL Amyloid Versus AA Amyloid
AL Amyloid = Misfolded proteins - affects all organs, not just kidneys = Tx Velcade
AA Amyloid - Due to raised amyloid A protein caused by chronic inflammation. Renal involvement = 100% = Tx IL-6 inhibitor such as Tociluzimab
Cryoglobulinaemia
Single or multiple immunoglobulins precipitate below 37oC. Cause immune complex deposition, and hyperviscority - depositing in small vessels.
More common in females and associated with hepatitis C
RF positive
Low C4 but normal C3
Cause mesangiocapillary GN
Diagnosing Amyloidosis
SAP scan -radioactive scan - goes to the deposited proteins and lights up showing the extent of the disease
Fat pad biopsy
Treatment of FSGS
1st line - Steroids for min 6/12
2nd line - CNI ( if no response to steroids after 6 months)
Alternatives = MMF or cyclo
Treatment of Membranous Nephropathy
1/3 will resolve spontaneously so watch / wait is reasonable
1st line - Ponticelli
2nd line - Tacrolimus - good at achieving remission but higher relapse rate
3rd Line - Rituximab - good at achieving remission but higher relapse rate
Lupus treatment
Induction = Steroids + MMF or Cyclophosphamide
Maintenance = MMF or Aza
Give hydroxychloroquine and supportive treatment as well
In diffuse proliferative GN - give cyclo
GPA
PR3 +Ve
cANCA
70% renal involvement
Higher relapse rate
Pulmonary, nose bleeds and eye involvement, hearing loss
MPA
MPO positive
pANCA
90% renal involvement
Bronchiectasis and pulmonary fibrosis
eGPA
MPO positive
pANCA
Sinus and asthma symptoms
Neurological involvement / mononeuritis multiplex is common
40% renal involvement
Frequent relapse
Features of a high risk IgA patient
Increased age
Reduced eGFR
Increase UPCR
Hypertension
Crescents on renal Bx
Treatment of Anti-GBM
1) PLEX
2) Steroids
3) Cyclophosphamide
How to tell the difference between IgA and post strep infection - in a patient that presents with sore throat, hematuria and renal impairment
IgA nephritis - onset of haematuria and sore throat very quickly together
In post-streptococcal glomerulonephritis the onset of renal disease is usually some time (weeks) after the upper respiratory illness.
Types of Membranoproliferative glomerulonephritis
also known as mesangiocapillary glomerulonephritis
Membranoproliferative glomerulonephritis - is a term to describe the pattern of injury
Historically 3 types depending on where the deposits were.
Now the 2 main types:
Type 1 = Immune complex related / IgG mediated disease. Occurs secondary to infection e.g Hepatitis, Autoimmune e.g lupus or myeloma. Tend to subendothelial deposits and IgG and C3 deposition within the mesangum. Associated with cryoglobulinemia. Can be idiopathic.
Type 2 = Dense deposit disease / non IgG mediated disease- now mainly known as C3 glomerulopathy. Deposition of C3 within the glomeruli with little or no staining for immunoglobulin. Low C3/C4
(Type 3 - rare - mainly rare inherited form with disruption to BM)
Complements in MCGN
Type 1 = Classical pathway activation. Normal C3, low C4
Type 2 = Alternative pathway - Normal C3 normal C4, plus C3 nephritic factor
Features and Treatment of HSP
present 1-3 days post infection of an IgA mucous membrane (e.g pharyngitis or GI).
Painless haematuria and less commonly nephrotic syndrome.
Rash (cutaneous vasculitis), abdo pain (GI vasculitis) - leading to bloody diarrhoea. Arthralgia.
All patients with HTN and proteinuria (>1 g/day) should be started on an ACEi
If the renal Bx shows crescentic GN, then an IS regime similar to that used in renal vasculitis should be started (high dose steroids +/- cyclophosphamide).
Lipoprotein glomerulopathy
Rare inherited disease seen in male Japanese patients
Presents with UPCR, nephrotic, ESRD
Mutation of APOE gene
Lipid thrombi accumulate in glomerular capillaries
Stain positive with oil red O stain
BP and UPCR aim in IgA
BP 120/80
UPCR <0.5
Poor prognostic features in FSGS
Renal impairment
Hypertension
Collapsing variety
High IFTA
Btw risk factors in MN - when to anticoagulate
Albumin <20
? > 8g/24hrs
If albumin <25 but another high risk feature e.g Obesity, UPCR >10g)
Where are the deposits with the types of membranoproliferative GN
Type 1 - Immune complex = subendothelial immune deposits, associated with hep C / cryo
Type 2- dense deposit disease / C3 GN = mesangial and intramembranous deposits
Antibody MCD
Anti nephrin antibodies
Proteinuria - Which lambda and kappa associated with which pathology
Kappa LC = Monocolonal IgG deposition disease
Lambda LC = AL amyloid
Firbils and the sizes
Amyloid - 8-12nm, randomly arranged - will stain congo red
Fibrillary GN - 12-20nm, random - like amyloid fibrils but don’t stain positive for congo red
Immunotactoid - >30nm, arranged in parallel. hollow, associated with haematological maligancy
Which cause of deposits: - Subendothelial / Subepithelial / Intramembranous / Mesangial
Subendothelial
- lupus class 3-4 / MPGN
Subepithelial
- Membranous / Infection / Class 5 lupus
Intramembranous
- Dense deposit disease / C3
Mesangial
- IgA
Risk factors and features of Nodular glomerulosclerosis
Commonly seen in patients with smoking and hypertension history
Looks like diabetic nephropathy on Bx but no history of DM
Biopsy = Linear IgG, thickened BM and foot process effacement.
Myeloma Kidney = Cast nephropathy - features
Increased LC reacts with Tamm-Horsfall in DCT = forms plug and tubular / interstitial injury
On Bx = Fractured casts with increased cells around it. Massons trichrome positive for monoclonal LC + congo red positive
Monoclonal Immunoglobulin deposition disease - features
Deposition in BM and tubules
Different to Amyloid - as fibrils are non-organized and negative for congo red
Types
-Light chain - often Kappa
-Heavy chain - often lambda
-Both heavy and light chain
Patients present with proteinuria, hematuria, raised BP and renal impairment
Biopsy features = nodular sclerosising GN, Linear staining along GBM and tubules for LC/HC or LHC, non organized fibrils
Appearances can look similar to DN but IF positive for monoclonal LC
Indication for steroids and cyclophosphamide in IgA nephropathy
> 50% crescents
Rapidly progressive GN
Note - MMF in Chinese patients
