Glomerular diseases
Lecture-5Hazem.K.Al-Khafaji
Glomerular
FICMSdiseases
Department of internal medicine
College
of medicine
Lecture-4Al-Qadissyia University
Acute Nephritic Syndromes
Clinical types, associations & causes
Post streptococcal Glomerulonephritis
Subacute Bacterial Endocarditis
Lupus Nephritis( diagnostic criteria of SLE)
Anti-glomerular Basement Membrane
Disease(Goodpasture΄s syndrome)
IgA Nephropathy(henoch-SchÖnlein purpura)
ANCA Small Vessel Vasculitis
Membranoproliferative Glomerulonephritis
Mesangioproliferative Glomerulonephritis
Sub acute Bacterial Endocarditis
Endocarditis-associated glomerulonephritis is
typically a complication of subacute bacterial
endocarditis.
Particularly in patients who:
Remain untreated for an extended period •
of time
Have negative blood cultures •
Have right-sided endocarditis (IVDU) •
Subacute Bacterial Endocarditis
associated glomerulonephritis
Pathogenesis
Endocarditis is infection of endothelium of the heart &
blood vessels. The bacteremia accompanying endocarditis
persists over long periods of time and represents a
prolonged antigenic challenge to the immune system.
Various antibodies and immune complexes appear in the
blood—more so with longer duration of illness,antibodies
like IgG & IgM form circulating immune complexes and
activate complement system.These are of major
importance because they cause microvascular damage.
Renal deposition of circulating immune complexes ,
frequently result in glomerulonephritis & if deposited in
the skin cause vasculitic skin lesion.
Subacute Bacterial Endocarditis
associated glomerulonephritis
Grossly, the kidneys in subacute bacterial
endocarditis have subcapsular hemorrhages
with a "flea-bitten" appearance.
Microscopy on renal biopsy reveals a focal
proliferation around foci of necrosis associated
with abundant mesangial, subendothelial, and
subepithelial immune deposits of IgG, IgM, and
C3(immune complex).
Patients present with:
Gross hematuria•
Microscopic hematuria•
Pyuria•
Mild proteinuria•
RPGN with rapid loss of renal •
function(less common)
Primary treatment is eradication of the •
infection with 4–6 weeks of antibiotics,
and if accomplished early, the prognosis
for renal recovery is good.
Lupus nephritis
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS THE MOST COMMON
CONNECTIVE TISSUE DISEASE.BOUT 90% OF PATIENTS ARE
WOMEN.THE PEAK AGE OF AT ONSET 20-30YEARS A DISEASE OF
INCOMPLETELY UNDERSTOOD CAUSE THAT MAY PRODUCE VARIABLE
COMBINATIONS OF FEVER, RASH, HAIR LOSS, ARTHRITIS, PLEURITIS,
PERICARDITIS, NEPHRITIS, ANEMIA, LEUKOPENIA,
THROMBOCYTOPENIA, AND CENTRAL NERVOUS SYSTEM (CNS)
DISEASE. THE CLINICAL COURSE IS CHARACTERIZED BY PERIODS OF
REMISSIONS AND ACUTE OR CHRONIC RELAPSES. CHARACTERISTIC
IMMUNE ABNORMALITIES, ESPECIALLY ANTIBODIES TO A NUMBER OF
NUCLEAR AND OTHER CELLULAR ANTIGENS, DEVELOP IN PATIENTS
WITH SLE. THE DIAGNOSIS IS FACILITATED BY DETERMINING WHETHER
THE PATIENT HAS 4 OF THE 11 CLINICAL AND/OR LABORATORY
CRITERIA DEVELOPED FOR THE CLASSIFICATION (REVISED AMERICAN
RHEUMATISM ASSOCIATION CRITERIA FOR SLE).
Butterfly rash of SLE
Typically bridge the nose & SPARES THE NASOLABIAL FOLDS
Renal disorder(criteria)
Persistent proteinuria >
0.5g ̸ day
or cellular casts(red cells,
granular or tubular.
Renal involvement due to anti -DNA Ab bind
Or precipitated in the glomeruli & induce
inflammatory reaction.GN may greatly
influence the course and therapy of SLE .
The incidence of clinically detectable renal
disease about 50%.
Histologic evidence of renal involvement by
immune deposits is found in the vast majority
of biopsy specimens, even in the absence of
clinical renal disease.
The World Health Organization (WHO)
classification of lupus nephritis has been
widely used for both clinical and research
activities . It has the advantages of using
LM, IF, and EM to classify each biopsy; of
separating the milder mesangial disease
from true proliferative lupus nephritis.
The WHO classes correlate well with the
clinical picture and subsequent course of
patients with SLE.
In general, all patients with class IV lesions
(diffused proliferative GN) had the worst
prognosis & require vigorous therapy for their
lupus nephritis. Vigorous lupus nephritis
therapy has included corticosteroids,
plasmapheresis, azathioprine, or
cyclophosphamide, as well as other more
recent immunosuppressive medications such
as cyclosporine, gamma globulin, and
mycophenolate mofetil. Plasmapheresis,
reported to be successful mode of treatment
ANTI-GLOMERULAR BASEMENT MEMBRANE
DISEASE(anti-GMB disease)
Goodpasture’s disease
THIS NEPHRITIS IS ONE OF RAPIDLY
PROGRESSIVE (CRESCENTIC) GN.
WITHIN DAYS-WEEKS RESULT IN
URAEMIA.
RPGN=RAPIDLY PROGRESSIVE URAEMIA
Pathogenesis
Due to deposition of IgG antibodies •
along the glomerular basement
membrane.
These antibodies deposited also in •
small vessels resulting in vasculitis &
sometime hemorrhage( mostly
pulmonary).
)
Cyclophosphamide,mycophenolate •
mofetil(celcept) or corticosteriods.
In case of severe nephritis & •
extrarenal manifestations
(pulmonary haemorrhage),plasma
exchange indicated.
IgA nephropathy
was originally thought to be an uncommon
and benign form of glomerulopathy (Berger's
disease). It is now recognized as the most
frequent form of idiopathic glomerulonephritis
worldwide (comprising 15 to 40% of primary
glomerulonephritides in parts of Europe and
Asia) and clearly can progress to ESRD. The
predominant antibody is composed of
polymeric IgA1 .The antigen-whether
infectious dietary or other-to which it is
directed is unknown in the majority of cases.
IgA nephropathy
Patterns of clinical presentation of IgA •
nephropathy
Common •
Asymptomatic haematuria +/- proteinuria
Hypertension
Chronic renal failure
Henoch-SchÖnlein purpura
Uncommon •
Malignant hypertension
Acute nephritic syndrome
Acute Kidney injury
Nephrotic syndrome
Henoch – SchÖnlein purpura
Henoch-Schönlein purpura (HSP) is characterized •
by a small-vessel vasculitis with arthralgias, skin
purpura, and abdominal symptoms along with a
proliferative acute glomerulonephritis that has
similar histopathologic features to IgA
nephropathy. HSP is predominantly a disease of
childhood, although cases do occur in adults.
Despite the finding of circulating IgA-containing
immune complexes, no infectious agent or allergen
has been defined as causative.
What are the symptoms of Henoch-Schönlein purpura? •
Typical HSP skin rash •
The main symptom of HSP is a painless rash (purpura) that usually appears on the •
legs, buttocks, and arms (though it can occur elsewhere). The rash starts off as
red dots, then turns purple over a period of three to six days and looks like
bruises. The rash does not change color when it is pressed on.
The symptoms of HSP are often preceded by cold and flu symptoms, such as •
fever, headache, nausea, loss of appetite, or diarrhea.
The other main symptoms of HSP are: •
Abdominal pain: Approximately two-thirds of children with HSP have abdominal •
pain, which may be accompanied by vomiting. Occasionally, blood may appear in
a child’s vomit or stool. Rarely, patients develop an abnormal bowel folding
called intussusception.
Joint pain: Children with HSP often have swelling and tenderness in the knees, •
ankles, elbows, and wrists. The swelling usually lasts 1-3 days. Sometimes whole
limbs will swell. The inflammation does not cause crippling arthritis.
Boys with HSP may also have painful swelling in the scrotum. •
HSP can also affect the kidneys, and patients may have features of •
glomerulonephritissmall amounts of blood in the urine. Between 20 and 50
percent of children with HSP have GN. The majority of these kidney problems
resolve (get better) over 6 months.
Symptoms usually last between 2 - 12 weeks, typically about a month. •
Recurrences are not frequent but do occur.
Palpable purpura . Here they are occurring in a very dense pattern with
coalescing lesions.
Arm rash . It is more common to have a purpuric outbreak on the
lower extremities. However, an outbreak can occur on the abdomen,
chest, or as in the case with this woman, on the upper extremities
Swelling around the hand and wrist . Although arthralgias are more common
in HSP, arthritis can occur as well as periarticular swelling, such as the
tenosynovitis shown here.
Treatment
Like IgA nephropathy, HSP has no proven therapy.
Episodes of rash, arthralgias, and abdominal
symptoms usually resolve spontaneously. Some
patients with severe abdominal findings have been
treated with short courses of high doses of
corticosteroids. Patients with severe glomerular
involvement may benefit by modalities used to treat
patients with severe IgA nephropathy. Although
most patients with HSP recover fully, patients with a
more severe nephritic or nephrotic
presentation(usually adults) and more severe
glomerular damage on renal biopsy have an
ANCA Small Vessel Vasculitis
Antineutrophil cytoplasmic antibodies(ANCA) of •
IgG type directed againist cytoplasmic constitute of
granulocyte,resultin in necrosis of small blood
vessels & focal segmental(necrotising)
glomerulonephritis.there is extracapillary
proliferation in the absence of significant
glomerular immune deposits(Pausi-immune GN).
10-40% of patients with rapidly progressive GN
may be ANCA positive.RPGN result in duplication
of serum creatinine during 3 months.
Clinical features
Occurs in older adults(50-60years) •
Associated with small-vessel systemic vasculitis in •
majority of patients (microscopic polyangiitis,
Wegener’s granulomatosis, Churg-Strauss syndrome)
Presents as rapidly progressive nephritis (dysmorphic •
erythrocytes, red blood cell casts, proteinuria)
Prodrome with fever or flu-like symptoms •
Skin: purpura and petechiae •
Wegener’s granulomatosis: granulomatous •
inflammation of the respiratory tract with pulmonary
renal syndrome (hemoptysis, dyspnea); antibodies are
commonly of PR3-ANCA (cANCA) specificity In renal
limited forms.
Treatment
may use one or more of these medication combinations to induce
remission:
Corticosteroids: Prednisilone , prednisone , Medrol , cortisone or
dexamethasone.
Biologic Therapy: Rituximab is a biologic protein chimeric monoclonal
antibody drug that attacks the B- cells, which are the precursors to
cells that make antibodies. This type of treatment is considered a form
of passive immunotherapy. Responses to ritxumab reported in
patients with relapsing or refractory disease.
Immunosuppressive Drugs: These drugs inhibit or prevent activity of
the immune system. Some drugs include cyclophosphamide,
cyclosporine, azathioprine, and mycophenolate mofetil.
Plasmapheresis: An important use of plasmapheresis is in the therapy
that removes the ANCA from the blood, where the rapid removal of
disease-causing auto-antibodies from the circulation is required in
addition to other medical therapy to help prevent further damage.
Choose the most appropriate answer:
WHICH OF THE FOLLOWING IS FEATURE OF •
ANCA vasculitis & NEPHRITIS:
A-Disease of childhood. •
B- Immune complex mediated. •
C- Crescent formation is not reported. •
D- Absence of significant glomerular immune •
deposits.
E- Renal function tests normal in most cases. •
Write short notes about
Plasmapheresis &
therapeutic plasma
exchange? & mention its
indications in
glomerulonephritis?
Thank you
Next lecturs :
Nephrotic
syndrome