Download GLOMERULAR DISEASES

Lecture 2
 Minimal
change disease occurs at all ages but
accounts for nephrotic syndrome in most
children and about onequarter of adults. It is
caused by reversible dysfunction of podocytes.
 The presentation is with proteinuria or nephrotic
syndrome, which typically remits with highdose
corticosteroid therapy (1 mg/kg prednisolone for
6 weeks).
 Minimal change disease does not progress to
CKD but can present with problems related to the
nephrotic syndrome and complications of
treatment.
 The
primary, idiopathic form of MCD is very
responsive to steroids. Up to 95% of patients
achieve complete remission, defined as
proteinuria declining to levels below 300 mg/day
with stable renal function.
 Some patients who respond incompletely or
relapse frequently need maintenance
corticosteroids, cytotoxic therapy or other
agents.
 Secondary forms of MCD should be treated by
focusing on removal or mitigation of the inciting
insult, such as discontinuation of a certain drug
or treatment of an underlying malignancy.
 Primary
focal segmental glomerulosclerosis
(FSGS) can occur in all age groups. In
some patients, FSGS can have specific
causes, such as HIV infection, podocyte
toxins and massive obesity, but in most
cases the underlying cause is unknown
(primary FSGS).
 Patients with primary FSGS present with
massive proteinuria and idiopathic
nephrotic syndrome.
Histological analysis shows sclerosis affecting
segments of the glomeruli, which may also
show non specific traping staining deposits
of C3 and IgM on immunofluorescence.
 Since FSGS is a focal process, abnormal
glomeruli may not be seen on renal biopsy if
only a few are sampled, leading to an initial
diagnosis of minimal change nephropathy.
 Juxtamedullary glomeruli are more likely to be
affected in early disease.

 Although
nephrotic syndrome is typical,
some patients present with the histological
features of FSGS but less proteinuria.
 In these patients, the focal scarring may
reflect healing of previous focal glomerular
injury, such as HUS, cholesterol embolism
or vasculitis. These examples of secondary
FSGS have different course and treatments.
 Primary
FSGS can respond to highdose
corticosteroid therapy (0.5–2.0 mg/kg/day) but
most patients show little or no response.
 Immunosuppressive drugs, such as ciclosporin,
cyclophosphamide and mycophenolate mofetil,
have also been used .
 Progression to CKD is common in patients
who do not respond to steroids and the
disease frequently recurs after renal
transplantation, with an almost immediate
return of proteinuria following transplant in some
cases.
membranous nephropathy, is the most common
cause of nephrotic syndrome in adults. It is caused
by antibodies (usually autoantibodies) directed at
antigen(s) expressed on the surface of podocytes.
 Recent studies suggest that one such antigen is the
Mtype phospholipase A2receptor1 (antiPLAR2 Abs).
 A proportion of cases are associated with other
causes, such as heavy metal poisoning, drugs,
infections and tumours and but most are
idiopathic.
 Approximately onethird of patients with idiopathic
membranous glomerulonephritis undergo
spontaneous remission; onethird remain in a
nephrotic state, and onethird go on to develop CKD.

 Shortterm
treatment with high doses of
corticosteroids and cyclophosphamide may
improve both the nephrotic syndrome and
the longterm prognosis. However, because
of the toxicity of these regimens, many
nephrologists reserve such treatment for
those with severe nephrotic syndrome or
deteriorating renal function.
 This
is one of the most common types of
glomerulonephritis and can present in many
ways . Haematuria is the earliest sign and is
almost universal, and hypertension is also very
common.
 Proteinuria can also occur but is usually a later
feature. In many cases, there is slowly progressive
loss of renal function leading to ESRD. Clinical
presentations are protean and vary with age.
 A particular hallmark of IgA nephropathy in young
adults is the occurrence of acute selflimiting
exacerbations, often with gross haematuria, in
association with minor respiratory infections.
 This
may be so acute as to resemble acute
postinfectious glomerulonephritis, with fluid
retention, hypertension and oliguria with dark
or red urine.
 Characteristically, the latency from clinical
infection to nephritis is short: a few days or
less.
 Asymptomatic presentations dominate in older
adults, with haematuria, hypertension and loss of
GFR. Occasionally, IgA nephropathy progresses
rapidly and crescent formation may be seen.
 The prognosis is usually good, especially in those
with normal blood pressure,normal renal
function and absence of proteinuria at
presentation.Surprisingly, recurrent macroscopic
haematuria is a good prognostic sign.
 The
management of less acute disease is largely
directed towards the control of blood pressure in
an attempt to prevent or retard progressive renal
disease.
 There is some evidence for additional benefit
from several months of highdose corticosteroid
treatment in highrisk disease, but no strong
evidence for other immunosuppressive agents.
 All patients with or without hypertension
and
proteinuria, should receive ACE inhibitor and/or
angiotensin II receptor antagonist which
enhances reduction of proteinuria and
preservation of renal function.
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Lecture 3
 This
condition most commonly occurs in
children but can also be observed in adults.
It is characterised by a systemic vasculitis
that often arises in response to an
infectious trigger.
 The presentation is with a characteristic
petechial rash typically affecting buttocks and
lower legs, and abdominal pain due to the
occurrence of vasculitis involving the
gastrointestinal tract.

 The
gastrointestinal disease, which occurs
secondary to submucosal edema and
hemorrhage, may be limited to pain and
vomiting. Some patients, however, may
experience more significant complications,
such as frank gastrointestinal hemorrhage or
intussusception.
 Less common systemic manifestations
include scrotal pain or swelling, as well as
central nervous system disease (i.e.,
headache, seizures).
 The
presence of glomerulonephritis is usually
indicated by the occurrence of haematuria.
When Henoch–Schönlein purpura occurs in older
children or adults, the glomerulonephritis is
usually more prominent and less likely to
resolve completely. Renal biopsy shows
mesangial IgA deposition and appearances that are
indistinguishable from acute IgA nephropathy.
 Treatment is supportive in nature; in most
patients, the prognosis is good, with
spontaneous resolution,
but some, particularly adults, progress to
develop ESRD.
 MPGN
is characterised by an increase in
mesangial cellularity with thickening of
glomerular capillary walls and subendothelial
deposition of immune complexes and/or
components of the complement pathway.
 The typical presentation is with proteinuria
and haematuria.
It can be classified into two main subtypes.
 The first is characterised by deposition of
immunoglobulins within the glomeruli. This subtype
is associated with chronic infections, autoimmune
diseases and monoclonal gammopathy.
 The second is characterised by deposition of
complement in the glomeruli and is associated with
inherited or acquired abnormalities in the
complement pathway. Within this category is socalled ‘dense deposit disease’”DDD”, which is
typified by deposition of electrondense deposits
within the GBM.
 The third subtype is recognised, in which neither
immunoglobulins nor complement are deposited
in the glomeruli. This is associated with healing
following thrombotic microangiopathies, such as HUS
and TTP.
 Treatment
of MPGN associated with
immunoglobulin deposits consists of
identifying and treating the underlying
disease, if possible, and the use of
immunosuppressive drugs such as
mycophenolate mofetil or
cyclophosphamide.
 There is no specific treatment for MPGN
associated with deposition of complement in
the glomeruli or for dense deposit disease.
Glomerulonephritis may occur in connection with
infections of various types, including subacute
bacterial endocarditis.
 The most common histological pattern in bacterial
infection is mesangiocapillary glomerulonephritis,
often associated with extensive immunoglobulin
deposition in the glomeruli with evidence of
complement consumption (low serum C3).In the
developed world, hospitalacquired infections with
various organisms are a common cause of these
syndromes.
 Worldwide, glomerulonephritis more commonly
follows hepatitis B, hepatitis C, schistosomiasis,
leishmaniasis, malaria and other chronic infections.
Infection with HIV may be associated with FSGS ,
particularly in people of African descent.

 This
is a specific subtype of postinfectious
glomerulonephritis. It is much more common
in children than adults .
 The latency is usually about 10 days after a throat
infection or longer after skin infection,
suggesting an immune mechanism rather than
direct infection.
 An acute nephritis of varying severity occurs.
Sodium retention, hypertension and oedema are
particularly pronounced. There is also reduction
of GFR, proteinuria, haematuria and reduced
urine volume. Characteristically, this gives the
urine a red or smoky appearance.
 Serum
concentrations of C3 and C4 are typically
reduced, reflecting complement consumption , and
evidence of streptococcal infection (High
“antistreptolysin O “ASO titer) may be found.
 Renal function begins to improve spontaneously
within 10–14 days, and management by fluid and
sodium restriction with diuretic and
antihypertensive agents is usually adequate.
 Remarkably, the renal lesion in almost all children
and many adults seems to resolve completely,
despite the severity of the glomerular inflammation
and proliferation seen histologically.
Rapidly progressive glomerulonephritis (also
known as crescentic glomerulonephritis) is
characterised by rapid loss of renal function over
days to weeks.
 Renal biopsy shows crescentic lesions, often
associated with necrotising lesions within the
glomerulus, termed focal segmental (necrotising)
glomerulonephritis. It is typically seen in
Goodpasture’s disease, where the underlying
cause is the development of antibodies to the
glomerular basement membrane (antiGBM
antibodies), and in smallvessel vasculitides .
 It can also be observed in SLE and occasionally IgA
and other nephropathies. Rapid onset disease may
be associated with relatively little proteinuria .

 Management
depends on the underlying cause
but immunosuppressive drugs are often
required. Patients with antiGBM disease should
be treated with plasma exchange combined
with corticosteroids and immunosuppressants
(cyclophosphamide).
 Patients with renal involvement secondary to
ANCAassociated vasculitis and SLE should also be
treated with corticosteroids and
immunosuppressants.
 Plasma exchange
:to remove circulating
antibodies
 Steroids: to suppress inflammation from antibody
already deposited
in the tissue.
 Cyclophosphamide: to suppress further antibody
synthesis
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