Week 4 - I(1) - Glomerulonephritis types Flashcards
What are the main types of glomerulonephritis? - they get their name from their morphological appearance
Minimal change disease
Focal Segmental Glomerulosclerosis
Membranous
Membranoproliferative
Rapid progressive glomerulonephritis
IgA nephropathy
What will effacement of the podocytes cause?
This will cause minimal change disease - associated with the loss of the size and charge selective barrier
In minimal change, unsure of what the circulating antibody is
Will this cause nephrotic or nephritic?
this causes nephrotic syndrome
Because minimal change disease is minimal, what can you see it on?
Cannot see it on light microscopy or immunoflorurescence but can see the change on electron microscopy
What is the commonest cause of nephrotic syndrome in children? What is the commonest cause of nephrotic syndrome in adults?
Children - minimal change disease - 77%
Adults - focal segemental glomerular sclerosis
What is the 1st and 2nd line treatment for minimal change disease?
1st line - steroids oral
2nd line - cyclophosphamide or ciclsporin (CSA)
Does minimal change disease cause progressive renal failure?
NO It can be associated with Il-13
Commonest cause of nephrotic syndrome in adults (35%) ? What may it be due to?
FSGS
Can be due to HIV, heroin, Obesity, reflux nephropathy
What does the renal biopsy of FSGS on light microscopy show?
It shows as the name suggests - focal segmental glomerulasclerosis
Can see the FSGS on the right glomerulus
What percentage of patients achieve remission on steroids? What percentage progress to ESRD over 10years?
60% patinets achieve remission with prolonged steroids
50% progress to ESRD after 10 years
What is the second most common cause of nephrotic syndrom in adults?
Membranous nephropathy
What are the important secondary causes of membranous nephropathy?
Hep B, Lupus, Gold, penicillamine. Also carcinomas
What is seen on renal biopsy in membranous glomerulonephritis?
Renal biopsy: diffusely thickened basemement membrane due to subepithelial immune complex deposition (creates a spike and dome apperance)
What is given as the treatment of membranous nephropathy? (same as the others)
Steroids + cyclophasphamide
What is the antibody that can be tested for in membranous nephropathy?
Test for anti-phospholipase A2 antibody - it is present in more than 70% of patients
The antigen is within the podocyte – call phospholipase A2 receptor (PLA2r) The antibody then attacks this in membranous nephropathy Again state the antibody and the important secondary causes?
Antibody - anti - PLA2 (anti-phospholipase A2) receptor antibody Hepatitis B, lupus, gol & penicillamine (and malignancies)
Because in membranous nephropathy, there is the deposition of the complexes in the glomerular membrane, what does it look like on light microscopy?
Thickened Basement Membranes - Silver Stain
What is the commonest glomerulonephritis in the world?
IgA nephropathy
Asymptomatic microhaematuria +/-non-nephrotic range proteinuria
What typically comes pre IgA nephropathy?
Resp or GI infection typically - usually causes macroscopic haematuria
What disease is IgA nephropathy associated with?
Associated with Henoch Schnolein Purpuura
What does IgA nephropathy show on renal biopsy?
On renal biopsy - Mesangial cell proliferation and expansion on light microscopy with IgA deposits in mesangium on IF
What percentage of people with IgA nephropathy progress to renal failure in 10-30 years?
25%
In IgA nephropathy, it is different to the other glomerulonephrtiis as the immune complexes form in the circulation Where do the immune complexes then deposit?
They deposit in the mesangial cells of he kidney
Does IgA nephropathy lead to nephrotic or nephritic syndrome?
Leads to nephritic syndrome
What are some of the secondary causes of IgA nephroapthy?
HSP
upper GI infection
URTI / post-strep / sore throat
What is the difference in timing between IgA nephropathy vs post-infectious glomerulonephritis?
IgA characteristically causes visible haematuria a few days after URTI
Post-infectious GN has lag time of around 2 weeks before haematuria occurs and would be a less benign presentation if associated with visible haematuria).
A treatable cause of acute renal failure Rapid deterioration in renal function over days/weeks Active urinary sediment (RBC’s, RBC & Granular Casts) May be part of systemic disease. Associated with glomerular crescents on biopsy. What is this?
This is rapidly progressive glomerulonephritis
What is RPGN associated with on biopsy? What disease do you think?
Associated with glomerular crescents on biopsy
Either think ANCA positive or ANCA negative vasculitis
Name 3 ANCA positive and 3 ANCA negative causing conditions of RPGN?
ANCA positvie - GPA, EGPA, MPA
ANCA negative - Goodpastures, SLE, HSP
Treatment should be prompt and consist of strong immunosuppression with supportive care including dialysis if needed What is the treatment given in RPGN?
Steroids (IV Methylprednisolone / Oral Prednisolone)
Cytotoxics (Cyclophosphamide/ Mycophenolate/ Azathioprine
74 year old woman. Hypoxic. Haemoptysis. creat 430. blood and protein on dip. Red cell casts on microscopy. Purpuric rash. Cells affected? Diagnosis? What test next?
Cells affected - endothelial cells
Diagnosis - RPGN - Goodpastures or ANCA +ve vasculitis
Next test - test for anti-GBM and ANCA
QUIZ STUFF First and second most common cause of nephrotic syndrome in adults? Most common cause in children? Most common glomerulonephritis in the world and what it cause?
Nephrotic syndrome in adults:
Most common - focal segemntal glomerulosclerosis
Second - membranous
Nephrotic in children - minimal change disease
Most common GN in the world is IgA and it causes nephritic syndrome
What is minimal change disease caused by? What is the treatment? What imaging is required?
Caused by effacement (fusion) of podocytes
Requires 1. Steroids 2. cyclophosphamid or ciclosporin (CSA) second line
Requires electron microscoopy as cant be seen on LM or IF
What type of drug is cyclophosphamide and what type is cyclosporin?
Cyclophasmphamide is an alkylating agent - cytotoxic
Ciclosporin is a calcineurin inhibtor
FSGS is the commonest cause of nephrotic in adults What percentage go onto renal failure? What percentage achieve remission on steroids?
50% are on ESRD after 10 years 60% achieve remission
What are secondary causes of FSGS?
HIV, Heroin, Obesity, Reflux nephropathy
What is seen on biopsy in FSGS?
Focal segmental glomerulosclerosis on light microscopy with minimal Ig/complement deposition on immunofluorescence
o Second commonest cause of nephrotic syndrome in adults (15-30%) What are some secondary causes?
This is mebranous nephropathy
Lupus, Hepatitis B, Gold and penicillamine
Maliganncies in patinets over 65
Membranous is treated with steroids/alylating agents/monoclonal antibody What are examples of alylating agents? What percentage are at ESRD after 10 years?
Alkylating agents - cyclophosphamide, tacrolimus
30% are on ESRD after 10 years
• IgA nephropathy (nephritic)
o Commonest glomerulonephritis in the world
o Asymptomatic microhaematuria.
IgA deposits causes immune complexes and deposits in the mesangial cells What is the treatment? What is seen on renal biopsy? What is prognosis?
Treatment - control blood pressure
Renal biopsy - mesagial cell proliferation on light microscopy, IgA deposits in the mesangium on immunoflouresence
Prognosis - 25% progress to ESRD in 10-30 years
What are some secondary causes of IgA nephropathy?
HSP, Upper resp/GI infection
Diffusely thickened GBM with IgG and C3 sub-epithelial deposits on immunofluorescence ?
This is mebranous nephroapathy
Which glomerulonephritis is associated with anti-PLA2 (anti-phospholipase A2) antibodies?
This is seen in membranous nephropathy
Whata re the antibodies measured in wegeners? Measured in microscopic polyangiits? Measured in lupus? Measured in Goodpastures syndrome?
Wegener’s - c-ANCA (PR3)
MPA - p-ANCA (MPO)
LUPUS - ANA - antidsDNA, anti-Sm
Goodpastures - glomerulonephritis with pulmonary alveolar haemorrhage - anti-GBM
What is the treatment of rapidly progressive glomerulonephritis?
Steroids (IV Methylprednisolone / Oral Prednisolone)
Cytotoxics (Cyclophosphamide/ Mycophenolate/ Azathioprine and Plasmapheresis
What is RPGN associated with on biopsy?
Associated with glomerular crescents on biopsy
o 25% progress to end stage renal failure in 10-30 years
o 50% progress to end stage renal failure after 10 years
o 30% progress to end stage renal failure in 10 years
o Does not cause progressive renal failure
Which GN is each?
o 25% progress to end stage renal failure in 10-30 years - IgA nephropathy
o 50% progress to end stage renal failure after 10 years - FSGS
o 30% progress to end stage renal failure in 10 years - Membranous nephropathy
o Does not cause progressive renal failure - minimal change disease
Which of the nephropathys causes nephritic syndrome?
this would be IgA mediated nephropathy
4 – What type of glomerular nephritis is associated with heroin use? A – Minimal change GN B – Focal segmental GN C – Membranous GN D – Membranoproliferative GN E – IgA GN F – Rapidly progressive GN
B - Focal segmetnal glomerulonephritis
- What type of glomerular nephritis shows changes to podocytes? A – Minimal change GN B – Focal segmental GN C – Membranous GN D – Membranoproliferative GN E – IgA GN F – Rapidly progressive GN
A - Minimal change nephropathy
What type of CKD is this? eGFR 60, no evidence of kidney disease.
Not CKD
– What type of CKD is this? eGFR 60ml/min PmHx – Hemodialysis.
Stage 5 kidney disease
What is renal osteodystrophy? A – hereditary malformation of the kidney B – hereditary malformation of bone C – chronic decreased hydroxylation of Vitamin D in CKD D – decreased bone density due to low BMI E – pathological fractures found in AKI F – increased width of bone found in AKI
C – chronic decreased hydroxylation of Vitamin D in CKD
Renal osteodystrophy has been classically described to be the result of hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney It weakens your bones
