1. Glomerulonephritis is a general term for
a group of disorders in which:
there is primarily an immunologically
mediated injury to glomeruli, although renal
interstitial damage is a regular
accompaniment
the kidneys are involved symmetrically
secondary mechanisms of glomerular injury
come into play following an initial immune
insult (see below)
the renal lesion may be part of a
generalized disease (e.g. systemic lupus
erythematosus, SLE).
2. Pathogenesis
Pathogenetic mechanisms include:
deposition or in situ formation of
immune complexes
deposition of antiglomerular
basement membrane antibody
(fewer than 5% of
glomerulonephritides)
deposition of an immunoglobulin of
atypical configuration in glomeruli, as
in IgA nephropathy.
3. Immune complex nephritis
The antigen may be exogenous or endogenous:
exogenous (e.g. bacterial) - for example, a
nephritogenic Lancefield group A β-haemolytic
streptococcus can cause glomerulonephritis in
previously healthy individuals
endogenous - for example, patients with SLE may
form antibodies to host DNA, leading to a
glomerulonephritis.
Antiglomerular basement membrane (anti-
GBM) antibody.
They bind mainly to the non-collagenous domain of
the α-3 chain type IV collagen (COLIVα3).
Anti-GBM antibodies are of IgG type.
4. Secondary mechanisms of
glomerular injury.
Several events can be triggered by
the above immunological insults:
complement activation
fibrin deposition
platelet aggregation
inflammation with inflammatory
cytokine mechanisms and free
oxygen radical-induced damage.
7. I. Proliferative glomerulonephritis
Proliferative changes occur in many immune
complex-mediated nephritides and also in anti-
GBM nephritis.
1. Diffuse proliferative glomerulonephritis
all the glomeruli are similarly affected
presenting as an acute nephritis
commonly seen after a streptococcal infection.
2. Focal segmental glomerulonephritis
some of the glomeruli show proliferative changes
may occur as a primary renal disease
is also seen in SLE, subacute infective
endocarditis, with infected atrioventricular shunts
(shunt nephritis), and in disorders with IgA
deposits (e.g. Henoch-Schönlein purpura and IgA
nephropathy).
a severe focal necrotizing form is seen in
microscopic polyangiitis and Wegener's
granulomatosis.
8. 4. Proliferative glomerulonephritis with crescent formation
(rapidly progressive glomerulonephritis; RPGN) or
crescentic glomerulonephritis
'Сrescent' - an aggregate of macrophages and epithelial cells in
Bowman's space.
Crescents are associated with severe damage to the glomerular
tuft.
It particularly occurs in microscopic polyangiitis, Wegener's
granulomatosis and Goodpasture's syndrome.
4. Mesangiocapillary (membranoproliferative)
glomerulonephritis (MCGN)
type 1
– mesangial cell proliferation, with mainly subendothelial
immune complex deposition and apparent splitting of the
capillary basement membrane, giving a 'tram-line' effect.
– may be idiopathic or may occur with shunt nephritis.
– can be associated with persistently reduced plasma levels of
C3 and normal levels of C4.
type 2
mesangial cell proliferation with electron-dense, linear
intramembranous deposits that usually stain for C3 only.
may be idiopathic or may occur after measles.
partial lipodystrophy (loss of subcutaneous fat in various parts of
the body).
MCGN affects young adults.
9. II. Membranous glomerulonephritis
The main feature - thickening of the capillary
basement membrane because of immune
complex deposition.
Patients present with:
proteinuria
frank nephrotic syndrome.
III. Minimal-change glomerular lesion
(minimal-change nephropathy)
is most common in children, particularly males,
the glomeruli appear normal on light microscopy.
there is fusion of the foot processes of epithelial
cells (podocytes) on electron microscopy
neither immune complexes nor anti-GBM
antibody can be demonstrated by
immunofluorescence.
10. However, the immunological pathogenesis of
this condition is suggested by three
factors:
its response to steroids and
immunosuppressive drugs
its occurrence in Hodgkin's disease, with
remission following successful treatment
patients with the condition and family
members having a higher incidence of
asthma and eczema; remission following
desensitization or antigen avoidance has
been described.
Treatment: corticosteroids,
cyclophosphamide and ciclosporin.
11. IV. IgA nephropathy
tends to occur in children and young
males
focal proliferative glomerulonephritis with
mesangial deposits of IgA.
IgG, IgM and C3 may also be seen in the
glomerular mesangium.
Patients present with:
asymptomatic microscopic haematuria
recurrent macroscopic haematuria
sometimes following an upper respiratory
or gastrointestinal viral infection.
roteinuria
5% can be nephrotic.
12. Clinical features
Glomerulonephritis presents in
one of four ways:
asymptomatic proteinuria and/or
microscopic haematuria
acute nephritic syndrome (see
below)
nephrotic syndrome
chronic renal failure
13. Investigations
Stix methods:
Proteinuria
Haematuria or haemoglobinuria
Further investigations will include:
urine microscopy for red-cell casts
assessment of renal function by estimation
of serum urea, creatinine and endogenous
creatinine clearance
renal imaging, initially by excretion
urography.
14. Acute nephritic syndrome
This comprises:
haematuria (macroscopic or
microscopic) - red-cell casts are
typically seen on urine microscopy
proteinuria
hypertension
oedema (periorbital, leg or sacral)
oliguria
uraemia.
16. Management
corticosteroid therapy
immunosuppressive therapy
agents that alter coagulation and
platelet function.
The aim of management is to prevent
patients dying from pulmonary
oedema, uraemia or hypertensive
encephalopathy while awaiting
improvement in renal function.
17. Management in hospital
Most patients require:
daily recording of fluid intake and output
daily weighing (as a check on change in
body fluid status)
regular measurement of blood pressure
dietary protein restriction (only if severe
uraemia occurs)
salt restriction
fluid restriction (in oliguric patients)
diuretic therapy (e.g. furosemide given
orally or parenterally) and other
hypotensive agents (if mild-to-moderate
hypertension and oedema present)
penicillin (in patients with poststreptococcal
glomerulonephritis)
18. Management of life-threatening complications
1. Hypertensive encephalopathy
intravenous sodium nitroprusside or hydralazine.
parenteral diazepam (10 mg i.v)
2. Pulmonary oedema
high doses of furosemide parenterally
salt and water can be removed osmotically by
peritoneal dialysis, by haemofiltration, or by
ultrafiltration during haemodialysis.
3. Severe uraemia
peritoneal dialysis
haemodialysis
haemofiltration
Prophylactic penicillin (phenoxymethyl penicillin
500 mg daily) should be given to all individuals at
risk.
19. Other glomerular disorders
1. Focal segmental glomerulosclerosis
(FSGS)
The aetiology is unknown. All age groups
are affected.
presents as proteinuria or nephrotic
syndrome
is usually resistant to steroid therapy.
segmental glomerulosclerosis (on light
microscopy), which later progresses to
global sclerosis
deposits of C3 and IgM in affected portions
of the glomerulus (on immunofluorescence)
About 50% of patients progress to end-
stage renal failure within 10 years of
diagnosis.
20. 2. AIDS-associated nephropathy
The most common histological
abnormality is a focal
glomerulosclerosis.
A characteristic 'collapsed'
appearance of glomeruli is often seen
on light microscopy but is not unique
to the condition
Antiretroviral agents may result in
stabilization of renal function.
21. Henoch-Schönlein syndrome
– skin rash (purpuric type)
– abdominal colic
– joint pain
– glomerulonephritis.
Is mainly a disease of early childhood.
Males are twice as often affected as females.
A recent history of infection, often respiratory, is
common.
Serum concentrations of IgA are increased in about
half the patients during the first 3 months of the
disease.
The renal lesion is a focal segmental proliferative
glomerulonephritis, sometimes with mesangial
hypercellularity.
Epithelial crescents may be present.
IgA deposition is seen in the glomerular mesangium.
IgG, IgM and components of the complement system
may also be detectable.
No treatment is of proven benefit.
22. Goodpasture's syndrome
is mediated by anti-GBM antibody
there is a strong association with
HLA-DR2.
Presents with:
1) recurrent haemoptysis
2) severe progressive proliferative,
often crescentic, glomerulonephritis
Treatment: plasma exchange (which
removes the anti-GBM antibody),
immunosuppressive therapy with
cytotoxic drugs and corticosteroids.
24. Patients present with:
fever,
arthralgia,
skin rashes
acute oliguric or non-oliguric renal failure
eosinophilia and eosinophiluria.
Renal biopsy: an intense interstitial cellular
infiltrate, often including eosinophils, with
variable tubular necrosis.
Treatment: involves withdrawal of offending
drugs. Prednisolone 60 mg daily. Dialysis (in
acute renal failure).
26. The patient presents with:
polyuria and nocturia,
proteinuria (slight - less than 1 g daily) or
uraemia.
Papillary necrosis the papillae can separate
and be passed in the urine
a sloughed papilla may cause ureteric colic or
produce acute ureteric obstruction.
Tubular damage defects in urine
concentration and sodium conservation
polyuria and salt wasting.
Fibrosis progressing into the cortex loss of
excretory function and uraemia.
27. Analgesic nephropathy
The chronic consumption of large amounts of analgesics
(especially those containing phenacetin) and NSAIDs leads to
chronic tubulointerstitial nephritis and papillary necrosis. COX II
specific NSAIDs are still being evaluated. In Australia, the
incidence of end-stage renal failure due to analgesic nephropathy
has declined as 'over-the-counter' purchase of nephrotoxic
analgesics has been reduced by legislation.
Clinical features
Analgesic nephropathy is twice as common in women as in men
and presents typically in middle-age. Patients are often depressed
or neurotic. Presentation may be with anaemia, chronic renal
failure, symptoms of urinary infection (which may be difficult to
eradicate), haematuria, or urinary tract obstruction (owing to
sloughing of a renal papilla). Salt and water-wasting renal disease
may occur.
Chronic analgesic abuse also predisposes to the development of
uroepithelial tumours.
Management
The consumption of analgesics should be discouraged. If
necessary, dihydrocodeine or paracetamol are reasonable
alternative choices. This may result in the arrest of the disease and
even in improvement in function.
UTI, hypertension (if present) and saline depletion will require
appropriate management.
28. Other forms of chronic tubulointerstitial nephritis
These are rare (see Table 11.14). Diagnosis of all forms
depends on a careful history being taken, with special
attention to drug-taking and industrial exposure to
nephrotoxins. In patients with unexplained renal
impairment with normal-sized kidneys, renal biopsy must
always be undertaken to exclude a treatable interstitial
nephritis.
Hyperuricaemic (gouty) nephropathy
Two patterns of renal disease have been described in patients
with hyperuricaemia or hyperuricosuria:
acute hyperuricaemic nephropathy
uric acid stone formation
There is no convincing evidence that chronic hyperuricaemia
per se causes progressive renal failure, nor that allopurinol
treatment improves renal function (see p. 554) There is
one exception: a rare form of familial hyperuricaemia and
gout occurring in adolescence is associated with renal
impairment and allopurinol therapy both improves and
protects kidney function.
