Glomerulonephritis Flashcards
Glomerulonephritis definition
inflammatory diseases involving the glomerulus and tubules
Nephrotic syndrome features:
“protein leac” (lipidaemia,oedema, albumin down, chol increases)
- Proteinurea (>3.5g in 24 hours)
- hypoalbuminaemia (<25g/l)
- peripheral oedema
- Hyperlipidaemia - total cholesterol >10mmol/l
Albumin is lost in the urine, due to gaps in podocytes allowing proteins to escape.
Oedema - due to loss of albumin, intravascular oncotic pressure decreases, fluid moves out of vessels
Hyperlipidaemia- hypoalbuminaemia, liver compensates by increasing production of lipids, hence causing hyperlipidaemia
Causes of Nephrotic syndrome
Primary
- minimal change glomerulonephritis - the most common cause of nephrotic syndrome in children
- membranous glomerulonephritis
- focal segmental glomerulosclerosis - the most common cause of nephrotic syndrome in adults
Secondary
- D - diabetes
- A - Amyloidosis
- V- vasculitis
- I - infections (syphillus, hep B_
- D- drugs
(SLE, malignancy, HIV)
Nephritic syndrome features
Blood +++ (microscopic or macroscopic)
Red cell casts- distinguishing features, form in nephrons and indicate glomerular damage
- Haematuria
- proteinuria (small amount)
- hypertension
- low urine volume <300ml/day
Causes of nephritic syndrome
Post sterptococcal glomerulonephritis - appears weeks after URTI
IgA nephropathy - appears within a day or two after URTI
Rapidly progressive glomerulonephritis (cresentic glumerulonehritis)
- Good pastures - anti-GBM Ab against basal membrane antigens
- vasculitic disorder- wegners, microscopic polyangitis
Tests for Glomerulonephritis
U&Es - creatinine for renal impairment
FBC- anaemia, infection
ESR, CRP- markers of inflammation (infectious cause_
EP and IG - IgA increased in IgA nephropathy EP rules out myeloma
Serum biochemistry- renal function, liver function, bone profile, lipids, glucose
Autoantibodies and complement
- ANCA- wegers granulomatosis + polyarterial nodosum
- Anti-GBM - good pastures
- ANF- lupus
Urinalysis, Urine PCR
- RBC casts, proteinuria
Coagulation screen
- biopsy (are they able to clot)
Imaging - CXR, US
- infection, pulmonary renal syndrom
LFTs (albumin levels)
GI - diabetes, commonest cause of all nephrotic syndromes
Feautures of IgA nephropathy
- Commonest cause of GN in the world
- may be secondary to:
- Henoch-schloen purpura
- cirrhosis
- coeliac disease
- may present with one or all
IgA nephropathy Clinical presentation
- Haematuria - increased destruction of GBM
- proteinuria
- hypertension
- renal impairment
Diagnosis of IgA nephropathy
- Electronmicroscopy - shows immune complexes in the GBM
- Immunofluorescence- shows IgA deposition
- Light microscopy- proliferation of mesangium
Pathophysiology of IgA nephropathy
- overproduction of IgA could be triggered by infection
- IgA deposition in the mesangium + C3 deposition
- Lysis of mesangium - Proliferation and activation of mesangial cells causing production of matrix - inducing glomerulosclerosis and scarring
- result is tubular loss, glomerulosclerosis and hypertensive damage
- Spillage of protein and blood cells into the urine
Treatment of IgA nephropathy
- No specific treatment
- Anti-hypertensives, ACE inhibitors
Outcomes of IgA nephropathy
- resolution
- Perists
- progression to ESRF 1/3
Membranous Glomerulonephropathy Clinical feautres
- proteinuria without haematura
- hypertension
- renail impairment
- Nephrotic syndrome!
Pathophysiology of Membranous glomerulonephritis
- Trigger may be Ag from tumour, infections, drugs
- Production of immune complexes, stuck in GBM
- alters GBM charg, permeability selectivity and thickened GBM
- Results in glomeruloscerlosis, tubular loss and hypertensive damage
- leads to loss of protein in urine = hallmark
Features of membranous GN
Treatment of membranous GN
Non specific therapy
- diuretics - furosemide
- ACE inhibitors - reduce proteinuria
- Statins
- consider anticoagulation -because of the hypervoagulable state associate with nephrotic syndrome
Specific
combination of
- prednisolone - dampen IC
- chlorambucil
No proven specific treatment wait for 6 months first due to rule of 30%
Rituximab has shown to be successful
Outcome of membranous GN
- 1/3 get resolution
- 1/3 peristent
- 1/3 progression to ESRF
Porticelli regimen
1 month of chorampuci/cyclophosphamide then 1 month prednisolone for 6 month period
treatment of membranous GN
Cresentic GN definition/ causes
Group of nephropathys associated with crescents on biopsys and with rapid progression to ESRF over a few weeks
Causes
- Goodpastures
- polyarteritis nodosa
- Wegeners granuloatosis
Goodpastures Pathophysiology
- Production of Anti-bodies against GBM plus Bm in lung (pulmonary renal syndrome)
- Deposition of Ab/complemet activation
- causes destruction of glomerular cells, proliferation of epithelial cells, crecent formation
- results in glomerulscerlosis, tubular loss and hypotensive damage
Good pastures clinical features
- Nephritic syndrome
- Haematuria
- Proteinruia
- Hypertension
- Renal impairment
Outcome of goodpastures
all will progress unless treated
Treatment of goodpastures syndrome
cytotoxic drugs to reduce antibody production
Pathophysiology of wegeners granulomatosis
- Necrotising granulomas of midline structures - nose, lungs, kidneys
- Necrotising vasculitis
- Nasal symptoms- bleeding, stuffiness and deafness
- Pulmonary symptoms - flitting opacities, pulmonary haemorrhage
- Crescentric glomerulonephritis - RPGN
Associated with anti-neutrophil antbody (ANCA)
Treatment of wegeners granulomatosis
Steroids, cytotoxics and spetrin
Rituximab is also effective - fever side effects
Untreated mortaility is 95% within one year
Post-infectious GN pathophysiology
- Post infection - stretococcal
- Production of AB/IC
- Deposition of ab/ic in mesangium and all throughout kidney
- complement is activated
- Reversible destriction of glomerular cells, proliferation of epithelial cells, crescent formation
Clinical features of Post-infectious GN
- haematuria
- proteinuria
- renal impairment
Treatment of post infectious GN
- self-limiting
- antibiotic therapy
Minmal change features
- commonest form of GN in children
- nephrotic syndrome
minimal change diagnosis
- lightmicroscopy will appear normal
- Electronmicroscopy - foot long procces, disruption to filtration barrier
- immunofluroscence - shows C3 and IgM deposition
Pathogenesis and cause of minimal change
T-cell mediated, cytokine mediated
Targets glomerulus, epithelial cells and GBM charge
Idiopathic but may be secondary to malignancys (lymphomas)
Treatment of minimal change disease
Curable
- high dose steroids - prednisolone
- cyclophosphamide- if they go into relapse
- cyclosporine- if the above doesnt work- steroid resistant or continually relapsing
Diabetic nephropathy incidence
Incidence
- Affects 35% of type 1 and increases rates of type 2
- Only affects a subset-not everyone
- Occurs after 10 years of diabetes
Clinical features of diabetic nephropathy
Clinical features
- Proteinuria and microalbuminaemia for years
- Hypertension (Nephrotic syndrome)
- Progressive ESRF
- Most patients die of CVD before ESRF
- ESRF
Histology and EM findings
Histology:
- Primarily endothelial dysfunction/damage affecting the glomerulus.
- Leads to nodular deposition of matric substance glomerulosclerosis- Kimmelstiel-Wilson nodule
- As the disease advances - GBM thickening with abnormal BM tht is leaky to protein
EM: glomerulular is uniformly thickened
Treatment of diabetic nephropathy
Treatment: ACEi limit proteinuria and control BP. No specific therapy.
Prevention of diabetic nephropathy
Glycaemic control in early years and BP control is imperative
