ACUTE POST STREPTOCOCCAL GN ( PSAGN)
Definition
-GN -Variety of renal diseases in which there
inflammation of the glomerulus, manifested by
proliferation of cellular elements secondary to an
immunologic mechanism.
-Most incidents of AGN appear to be associated with a
post infectious state ie post bacterial,viral and protozoan
infection eg staphylococcal , pneumonococcal
infections, coxsackievirus B, echovirus type 9, influenza
virus, and mumps.
PSAGN follows infection with group A beta hemolytic
streptococci.
Pathophysiology
-Immune complexes, preformed by the combination of
specific antibodies against streptococcal antigens,
localize on the glomerular capillary wall and activate
the complement system.
-The immunologic system may also be activated by
streptococcal antigens that adhere to the glomerular
structures and act as "planted antigens" or by alterations
in endogenous antigens.
-The activation of the complement cascade then
generates chemotactic -activated complement 5 (C5a)
and platelet-derived inflammatory mediators.
-Various cytokines and other cellular immunity factors
initiate an inflammatory response manifested by cellular
proliferation and edema of the glomerular tuft.
-Only some strains of Grp A strep are nephrotogenic.
Some non Grp A eg Grp C also cause PSGN.
-At least 2 antigens isolated from nephritogenic
streptococci, zymogen (a precursor of exotoxin B) and
glyceraldehyde phosphate dehydrogenase (GAPDH),
have been identified and are believed to be capable of
initiating the immunologic response
-Nodular deposits of immunoglobulin G (IgG) and the
third component of complement (C3) on the capillary
basement membrane. The finding of C3 in the renal
glomerulus is usually associated with decreased serum
concentrations of C3 and total hemolytic complement.
-C3 levels return to normal in children in 6-8wks in
children.C4 levels usually depressed too inconsistently.
-PSAGN can occur in epidemics or, more commonly, it
is be sporadic.
-The sporadic form is seasonal; is associated with
respiratory infection, and often associated with
pyoderma.
-Common group A beta hemolytic streptococci
associated with nephritis from nasopharyngeal
infections is type 12, type 49 is most often recovered
during outbreaks of pyoderma-related PSAGN.
-In individuals with pharyngitis-related AGN, the
latent period is approximately 10 days, and more than
80% of patients exhibit a significant rise in serum titer
of antistreptolysin-O (ASO). latent period is difficult
to define in persons with impetigo-related AGN, and a
rise in the titer of ASO only 50% of patients
Other streptococcal indicators (eg, antihyaluronidase
[AH] titer, antideoxyribonuclease B titer [anti-DNase
B]) elevated in either pharyngeal or skin infections.
-When a variety of antibody titers is used, almost 95%
of patients with PSAGN demonstrate evidence of a
prior streptococcal infection
Clinical Presentation:
Most patients with acute GN exhibit milder symptoms
between 2 extremes;
-Asymptomatic child whose disease is discovered only
by examination of the urine. Based on surveillance
studies of the siblings and/or household contacts of
children affected with PSAGN, at least 50% of persons
with laboratory evidence of nephritis (ie, abnormal
urinalysis) appear to have no symptoms or signs of
clinical illness
- Severe disease manifested by oliguria, edema,
hypertension, and azotemia and with proteinuria,
hematuria, and urinary casts (cylindruria).
Histology:
The glomerular tufts usually appear enlarged and
swollen; proliferation of mesangial and epithelial cells is
present. Polymorphonuclear leukocytes
Immunofluorescent microscopy Granular deposits of
IgG and C3 ; other immunoglobulins (Igs) and
fibrinogen often are observed.
Electron microscopy of renal tissue from patients with
PSAGN usually reveals subepithelial electron-dense
deposits (humps)
Usually, measurable reduction in volume of glomerular
filtrate (GF) is present, and the capacity to excrete salt
and water is usually diminished, leading to expansion of
the extracellular fluid (ECF) volume.
-The expanded ECF volume is responsible for edema
and, in part, for hypertension, anemia, circulatory
congestion, and encephalopathy.
Mortality/Morbidity:
Generally good prognosis
-Depends largely on the severity of the initial insult.
–In Very few of pts the initial injury is so severe that
either persistent renal failure or progression to chronic
renal failure occurs.
-In most patients, histologic regression of the disease
occur, and prognosis good.
-Clinical manifestations of the disease rarely recur after
the first 3 months, and second episodes of AGN are
uncommon.
-Poorer prognosis in adults, particularly in elderly
individuals.
Clinical course predictable:
 Edema usually resolves within 5-10 days
 Gross hematuria usually disappears within 1-
3 weeks
 BP usually returns to normal within 2-3
weeks though persistence of elevated
pressures for as many as 6 weeks is
compatible with complete resolution.
 The C3 concentration returns to normal by 6-8
weeks
 Urinary abnormalities resolve at slower pace.
Proteinuria may disappear within the first 2-
3 months or may decrease slowly over 6
months. Intermittent or postural proteinuria
has been noted in a few patients for as long as
1-2 years after onset.
 Microscopic hematuria usually disappears
after 6 months; however, its presence for as
long as 1 year is not uncommon
Possibility that the disease has entered a chronic phase
if both hematuria and proteinuria persist for more
than 12 months
Age:
-Greatest frequency in children aged 4-12 years, with a
peak prevalence in individuals aged approximately 5-6
years. Slight male predominance
Other postinfectious causes of AGN must be considered
in the differential diagnosis (eg, Strep pneumoniae,
Staph aureus, Staph epidermidis, Rickettsia rickettsiae,
Mycoplasma species, Meningococcus species,
Leptospira species).viral illnesses causing AGN; most
common varicella-zoster virus, cytomegalovirus, and
the Epstein-Barr virus
1.IgA-associated GN
-Urticarial or purpuric rashes, abdominal complaints,
and arthritis and/or arthralgia
-HTN and oedema less prominent.
-No evidence of prior strep infection and c3 levels