What are the causes of Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome and chronic kidney disease. It generally presents in young adults.
Causes
- idiopathic
- secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
- HIV
- heroin
- Alport’s syndrome
- sickle-cell
Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal transplants.
What are the renal biopsy findings in Focal Segmental Glomerulosclerosis?
focal and segmental sclerosis and hyalinosis on light microscopy
effacement of foot processes on electron microscopy
What glomerulonephritides normally present with nephritic syndrome?
Rapidly progressive glomerulonephritis - aka crescentic glomerulonephritis
- rapid onset, often presenting as acute kidney injury
- causes include Goodpasture’s, ANCA positive vasculitis
IgA nephropathy - aka Berger’s disease, mesangioproliferative GN
- typically young adult with haematuria following an URTI
- there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
What glomerulonephritides normally present with a mixed nephritic/ nephrotic picture?
Diffuse proliferative glomerulonephritis
- classical post-streptococcal glomerulonephritis in child
- presents as nephritic syndrome / acute kidney injury
- most common form of renal disease in SLE
Membranoproliferative glomerulonephritis (mesangiocapillary)
- type 1: cryoglobulinaemia, hepatitis C
- type 2: partial lipodystrophy
What glomerulonephritides normally present as nephrotic syndrome?
Minimal change disease
- typically a child with nephrotic syndrome (accounts for 80%)
- causes: Hodgkin’s, NSAIDs
- good response to steroids
Membranous glomerulonephritis
- presentation: proteinuria / nephrotic syndrome / chronic kidney disease
- cause: infections, rheumatoid drugs, malignancy
- 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease
Focal segmental glomerulosclerosis
- may be idiopathic or secondary to HIV, heroin
- presentation: proteinuria / nephrotic syndrome / chronic kidney disease
What disorders present with glomerulonephritis and low complement levels?
post-streptococcal glomerulonephritis
subacute bacterial endocarditis
systemic lupus erythematosus
mesangiocapillary glomerulonephritis
What is the renal biopsy finding for membranous glomerulonephritis?
electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a ‘spike and dome’ appearance
What are the causes of membranous glomerulonephritis?
- idiopathic: due to anti-phospholipase A2 antibodies
- infections: hepatitis B, malaria, syphilis
- malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
- drugs: gold, penicillamine, NSAIDs
- autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
What are the renal biopsy features of post-streptococcal glomerulonephritis?
post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis
endothelial proliferation with neutrophils
electron microscopy: subepithelial ‘humps’ caused by lumpy immune complex deposits
immunofluorescence: granular or ‘starry sky’ appearance
What are the causes of rapidly progressive glomerulonephritis?
Rapidly progressive glomerulonephritis is a term used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Causes
- Goodpasture’s syndrome
- Wegener’s granulomatosis
- others: SLE, microscopic polyarteritis
What are the causes of the 3 types of membranoproliferative (mesangiocapillary) glomerulonephritis?
Type 1
accounts for 90% of cases
-cause: cryoglobulinaemia, hepatitis C
Type 2 - ‘dense deposit disease’
-causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency
Type 3
-causes: hepatitis B and C
What are the renal biopsy features of Type 1 membranoproliferative glomerulonephritis?
electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a ‘tram-track’ appearance
What are the renal biopsy features of Type 2 membranoproliferative glomerulonephritis?
electron microscopy: intramembranous immune complex deposits with ‘dense deposits’
What is the pathophysiology of Type 2 membranoproliferative glomerulonephritis?
caused by persistent activation of the alternative complement pathway
low circulating levels of C3
C3b nephritic factor is found in 70%
an antibody to alternative-pathway C3 convertase (C3bBb)
stabilizes C3 convertase
What are the renal biopsy features of Class IV (diffuse proliferative glomerulonephritis in SLE?
-glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence
What are the causes of nephrotic syndrome?
Primary glomerulonephritis accounts for around 80% of cases
- minimal change glomerulonephritis (causes 80% in children, 30% in adults)
- membranous glomerulonephritis
- focal segmental glomerulosclerosis
- membranoproliferative glomerulonephritis
Systemic disease (about 20%)
- diabetes mellitus
- systemic lupus erythematosus
- amyloidosis
Drugs
-gold (sodium aurothiomalate), penicillamine
Others
- congenital
- neoplasia: carcinoma, lymphoma, leukaemia, myeloma
- infection: bacterial endocarditis, hepatitis B, malaria
