Glomerulonepheritis

Glomerulonephritis (GN) includes a variety of diseases with

diverse etiologies and variable morphologic appearances clinically
presenting with a nephritic syndrome. This include gross or microscopic
hematuria, proteinuria varying from minimal to moderate, casts on
urinalysis, fluid overload with hypertension, and variable degree of renal
insufficiency with oliguria or anuria.
According to the WHO classification of glomerulopathies, the most
frequently encountered forms of acute GN will either be found in a group
of primary glomerulopathies or in glomerulopathies secondary to
systemic disease.

A) Causes of hypocomplementic glomerulonephritis:

1- Acute poststreptococcal glomerulonephritis.
2- Lupus nephritis.
3- Shunt nepheritis.
4- Endocarditis.
5- Membranoproliferative glomerulonephritis.
6- Cryoglobulinemia.

B) Causes of normocomplementemic glomerulonephritis;

1- IGA nephropathy.
2- Mesangioproliferative glomerulonephritis.
3- Heamolytic uremic syndrome.
4- Anaphylactoid purpura nephritis.
5- Vasculitis.
6- Anti glomerular basement disease.

Acute Postinfectious Glomerulonephritis

Acute postinfectious glomerulonephritis (AGN) may occur at any

age, but it is more commonly encountered between the ages of 3 and 12
years. Geographical variations in the incidence of AGN are well known.
With improving living standards, the incidence has decreased in most
Western countries over the past half century but AGN is still a major
health concern in many geographic regions of the world. Because AGN
follows upper respiratory or skin infection with group A β-hemolytic
streptococcus in over 90% of cases, the term ‘acute poststreptococcal
glomerulonephritis’ (APSGN) is often used synonymously with AGN.
 Although much less common, AGN may result from a variety of
other bacterial and viral infections, such as staphylococci, pneumococci,
Yersinia, Mycoplasma pneumoniae, influenza virus, adenovirus,
coxsackie virus, cytomegalovirus, Epstein–Barr virus, varicella virus,
mumps virus, measles virus, and parvovirus B19. Rarely, AGN can occur
with chronic bacterial infections, such as subacute endocarditis,
ventriculoatrial shunt infections, and deep-seated abscesses.

Acute Poststreptococcal Glomerulonepheritis (APSGN)

Etiology:
- Follows infection of the throat or skin with nephritogenic strains of
group A ß hemolytic streptococci.
- APSGN commonly follows streptococcal pharyngitis in cold
weather. The commonest group A serotypes are M 1, 2, 3,4,12, 25
and 45.
- APSGN commonly follows streptococcal pyoderma in warm
months. The commonest group A serotypes are M 2, 47, 49, 55, 57
and 60.
- APSGN has been recently reported after group C and G
streptococcal infection; this is due to the common nephritogenic
antigen (endostreptosin), which has been isolated from these
strains.

Pathogenesis:
- Depression of serum C3 level strongly suggest that APSGN is
mediated by immune complexes formed against nephritogenic
streptococcal antigens.
- The proposed mechanisms are (1) deposition of circulating
immune complexes containing nephritogenic antigen in glomeruli,
(2) implantation of the nephritogenic antigen into glomerular
structures and in situ formation of immune complexes, (3)
molecular mimicry between streptococcal antigens and normal
glomerular antigens that react with antibodies against streptococcal
antigens, and (4) direct activation of the complement system by
implanted streptococcal antigens.

Patholgy:
1. Light Microscopy: All glomeruli appear enlarged and
relatively bloodless and show diffuse mesangial cell
proliferation and increased measngial matrix.
Polymorophnuclear leukocytes are seen in the glomeruli in
 the early stages of the disease and crescents may be seen in
severe cases.
2. Immunoflourescence Microscopy: lumpy-bumpy deposits
of immunoglobulin and complement are found on the GBM
and in mesangium.
3. Electron Microscopy: Electron dense deposits "humps" are
found on the epithelial side of GBM.

Clinical Manifestations:
- APSGN is most common in children aged 3-12 years. It is rare
below the age of 2 years and above 20 years.
- Twice more frequent in males than females.
- The usual sites of antecedent infection are throat and skin. The
latent period after skin infection is longer (3-6 weeks) than that
after throat infection (1-2 weeks).
- APSGN may present with sub clinical course, acute nephritic
syndrome or by complicated course.
2. Subclinical course: may be 9 times more frequent than
symptomatic cases. Characterized by reduction of serum
complement; microscopic haematuria, mild or moderate
proteinuria. Normal or increased blood pressure in an
asymptomatic child.
3. Nephritic Syndrome: characterized by dark coca colored urine,
edema, hypertension, oliguria, mild or moderate proteinuria.
- Dark colored urine: Glomerular haematuria is a universal
finding and gross hematuria is found in one third of patients.
- Edema: present in 90% of cases due to salt and water
retention. Appears in the form of puffiness of the eye lids
which is marked early in the morning associated with mild
bilateral pre-tibial pitting edema.
- Hypertension: in 60-80% of children. Hypertension in
APSGN is the low-renin type due to retention of water and
salt, which leads to expansion of the extracellular fluid
volume with consequent suppression of the renin-
angiotensin-aldosterone axis. Usually it is mild and has a
biphasic course.
- Oliguria: in around 50% of cases.

4. Complications of APSGN:
- AKI: in 25% of cases but the need for dialysis is infrequent.
It is characterized by oliguria to anuria, severe azotemia, and
acid–base and electrolyte disturbances. Hyperkalemia may
be a fatal complication due to cardiovascular effects, and
 requires urgent conservative treatment and dialysis Rapidly
progressive azotemia occurs in less than 0.5% due to the
development of crescentic glomerulonephritis.
- Circulatory congestion is the most common complication
in hospitalized children with APSGN. If severe, it can lead
to heart failure and pulmonary edema which represents an
emergency state and requires prompt and appropriate
therapy. The signs of circulatory congestions are
tachycardia, dyspnea, orthopnea, and cough.
- Hypertensive encephalopathy is found in 0.5% to 10% of
hospitalized patients. The most common clinical signs are
nausea, vomiting, headache, and impairment of
consciousness that varies from somnolence to coma. The
children may manifest seizures, hemiparesis, amaurosis, and
aphasia. These symptoms are a consequence of sudden
elevation of the blood pressure, which impairs cerebral
autoregulation leading to vasogenic edema. Nuclear
magnetic resonance imaging shows typical alteration of the
posterior white matter, which is termed reversible posterior
leukoencephalopathy syndrome. Neurological complication
in APSGN cannot be attributed exclusively to hypertensive
encephalopathy or abnormal serum biochemistry. With
advances in neuroimaging techniques, there is clear evidence
that some children may develop cerebral vasculitis.

Investigations:
A) Urine analysis:
- Glomerular haematuria as evidenced by presence of RBCS
casts and dysmorphic RBCS.
- Mild or moderate proteinuria.
B) Mild normochromic anemia from haemodilution.
C) Low serum C3 level is found in the acute phase and returns to
normal in 8 weeks.
D) Evidence of recent streptococcal infection by rising ASO titer
(usually –ve in skin infection) or better by Anti Dnase B level.
E) Renal biopsy is indicated in children with:
1- Atypical presentation: Absent evidence of
recent streptococcal infection, normal C3 level,
acute renal failure, nephrotic syndrome, marked
growth retardation and severe anemia.
2- Atypical resolution: Persistently low serum C 3
or impaired kidney function for 2 months,
 persistence of microscopic hematuria and / or
proteinuria for one year.
Differential Diagnosis:
1- Acute exacerbation of chronic glomerulonepheritis: may follow
upper respiratory tract infection. Usually associated with
marked growth failure and severe anaemia.
2- Other causes of acute post infectious glomerulonepheritis:
streptococcus pneumonia, staphylococci and gram –ve bacteria.
3- Lupus nephritis: Chronic course associated with arthritis,
photosensitivity, hemolytic anemia and carditis.
4- Anaphylactoid purpura nepheritis: associated with arthritis,
severe abdominal pain, skin rash and normal C3 level.
5- IGA Nephropathy: normal C3 level and elevated serum IGA
level.
6- Hemolytic uremic syndrome: haemolytic anemia,
thrombocytopenia and acute renal failure.
7- Bacterial endocarditis (embolic) nephritis.
8- Membranoproliferative glomerulonephritis.

Treatment of APSGN:
A) Bed rest and limited activity are indicated in the early stage of the
disease, particularly if circulatory overload and hyper-tension are
present.
B) Antibiotics:
- Limit the spread of nephritogenic strains but it will not
change the natural course of the disease.
- Single dose of long acting (benzathine) penicillin given IM
is sufficient (1200000 U in children weighted ≥ 27 Kg and
600000 u in children weighted < 27 kg).
- Oral penicillin V (250 mg/dose bid-tid for children < 27 kg
and 500 mg /dose bid-tid in children weighted ≥ 27 Kg)
- Macrolides are used in children with penicillin allergy (e.g.
erythromycin 40 mg/kg daily in divided doses orally for 10
days).
C) Treatment of edema by salt restriction and loop diuretics.
D) Treatment of hypertension by calcium channel antagonists
converting enzyme inhibitors or vasodilators.
E) Hyperkalemia should be prevented by restricting potassium intake.
If present, conservative treatment should be started immediately to
prevent fatal complications. Severe hyperkalemia, azotemia,
acidosis, uncontrolled hypertension, cardiovascular insufficiency,
and pulmonary edema are indications for immediate dialysis.
Prognosis:
- Complete recovery occurs in more than 95% of patients.
- Recurrences are very rare.