2. Definition
Acute glomerulonephritis (AGN) is a disease
characterized by the sudden appearance of
◦ edema,
◦ hematuria,
◦ proteinuria, and
◦ hypertension.
Inflammation of the glomerulus is manifested
by proliferation of cellular elements
secondary to an immunological mechanism.
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4. Pathophysiology
Acute poststreptococcal glomerulonephritis follows
infection by nephritogenic group A beta hemolytic
streptococci.
Both cellular and humoral immunity is important
Humoral immunity
Is mediated by nephritogenic streptococcal antigen-
antibody complexes and circulating immune
complexes.
These antigens bind to these sites within the
glomerulus and activate complement.
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5. Delayed-type, cellular
hypersensitivity
Resident endothelial and mesangial cells
proliferate accompanied by infiltration with
polymorphonuclear leukocytes and monocytes.
T-cell activation, with release of T-cell–derived
lymphokines such as interleukin 1 and
nterleukin 6.
Autologous immuno-
globulin G (IgG) in acute
poststreptococcal
glomerulonephritis
becomes antigenic and
elicits an anti-IgG response..
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6. Glomerular inflammation reduces glomerular filtration
The reduced volume of glomerular filtration and the
normal tubular function lead to an increase in the
reabsorption of salt and water, with resulting oliguria
and edema.
This is 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
The edema first collects in those sites where tissue
resistance is low, such as the periorbital area.
Later, it becomes more generalized, and, even may
simulate that of the nephrotic syndrome.
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7. Epidemiology
Usually occurs as sporadic cases
As many as 50% of cases may be subclinical;
thus, the true incidence of the disease is
unknown.
Most frequent in children aged of 2-12 years
Peak incidence in tropical countries during
summer and autumn.
A decline in the incidence of acute
poststreptococcal glomerulonephritis has
been reported over the last 2-3 decades.
Why?
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8. Clinical picture
A latent period of 7-21 days (average 10 days, for
pyodermal streptococcus infections longer!) is
characteristic.
At one extreme is the asymptomatic child whose disease
is discovered only by examination of the urine.
At the other extreme is the child who presents with
severe disease manifested by
◦ oliguria,
◦ edema,
◦ hypertension, and
◦ azotemia and with
◦ proteinuria,
◦ hematuria, and
◦ aurinary casts (cylindruria).
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9. Clinical picture
Gross hematuria and/or edema represent the most
common clinical presentation.
One or both findings usually appear abruptly and
may be associated with
◦ various degrees of malaise,
◦ lethargy,
◦ anorexia,
◦ fever,
◦ abdominal pain, and
◦ headache.
◦ joint aches
◦ muscle aches
◦ loss of appetite
Observant parents may also note oliguria.
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10. Edema
Edema is the most frequent manifesting
symptom.
According to some investigators, edema is
found in approximately 85% of patients.
Edema usually appears abruptly and first
involves the periorbital area, but it may be
generalized.
The degree of edema widely varies
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11. Hematuria
Gross hematuria occurs at onset in 30-50%
of children with poststreptococcal acute
glomerulonephritis who require
hospitalization.
The urine is smoky, cola colored, tea colored,
or rusty.
The color is usually dependent on the
amount of blood present and the pH of the
urine.
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12. Hypertension
Hypertension is reported in 50-90% of
children with acute glomerulonephritis.
The pathogenesis is multifactorial and related
only in part to extracellular fluid (ECF) volume
expansion.
The magnitude of the increase in blood
pressure (BP) widely varies;
systolic pressures greater than 200 mm Hg and
diastolic pressures greater than 120 mm Hg
are not unusual.
Hypertension persisting beyond the first week
may suggest a diagnosis other that acute
glomerulonephritis. WEBSTER
13. Circulatory congestion
Circulatory congestion is apparent in most
children admitted to the hospital
◦ Dyspnea, orthopnea, and cough may be present.
◦ Pulmonary rales are often audible.
◦ At times, the only evidence of congestion is detected
on chest radiograph.A prominent cardiac shadow may
be present.
Pallor is common at onset and is not explained
entirely by the anemia.
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14. Hypertensive encephalopathy
Hypertensive encephalopathy (5% of hospitalized
children) is the most serious early complication
In these patients, hypertension is usually severe
It is accompanied by signs of CNS dysfunction:
◦ headache,
◦ vomiting,
◦ confusion,
◦ visual disturbances,
◦ aphasia,
◦ memory loss,
◦ coma, and convulsions.
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15. Clinical course
The clinical course is largely predictable:
Edema usually resolves within 5-10 days, and
Blood pressure (BP) usually returns to normal within 2-
3 weeks, although persistence of elevated pressures for
as many as 6 weeks is compatible with complete
resolution.
Gross hematuria usually disappears within 1-3 weeks;
however, it subsequently may recur following physical
activity.
Proteinuria may disappear within the first 2-3 months or
may decrease slowly over 6 months.
Chronic phase if both hematuria and proteinuria persist
for more than 12 months.
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16. Physical examination
Edema may be either local (eg, periorbital) or
generalized.
Both systolic and diastolic hypertension may be
present to a varying degree.
Pallor is common.
In some patients, pulmonary rales are audible.
Either bradycardia or tachycardia may be
observed.
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17. Urinalysis
Examination of the urine under a
microscope
Urine RBC
Creatinine clearance
Total protein
Urine concentration test
Urine creatinine
Urine protein
Urine specific gravity
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18. Blood tests
Albumin
Urea and creatinine
Anti-glomerular basement membrane
antibody test
Anti-neutrophil cytoplasmic antibodies
(ANCAs)
Complement levels
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20. Management
Edema and circulatory congestion are
usually not sufficiently marked to produce
more than minimal discomfort.
Restriction of fluids to those amounts
needed to replace insensible losses is the
best treatment for edema and circulatory
congestion.
If congestion is marked, administer
Furosemide parenterally (2 mg/kg).
Diuretic agents (eg, furosemide) are rarely
necessary after the first 2 days;
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21. Management
Anuria or severe and persistent oliguria may
occur in 3-6% of children with acute
glomerulonephritis.
Fortunately, it is usually transient.
Because they may be ototoxic, avoid large
doses of Furosemide
Osmotic diuretics, such as Mannitol, are
contraindicated as they might increase vascular
volume.
Dialysis in these cases may be necessary
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22. Management
A course of penicillin to avoid contamination of
contacts but it does not influence the course of the
disease
Throat cultures of immediate family members
might detect patients who are asymptomatic but
infected.
Steroid therapy is indicated only in patients with
severe non streptococcus glomerulonephritis or in
those with rapidly progressive glomerulonephritis.
Treat hypertension (see below)
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23. Diet
A low-sodium, low-protein diet during the
acute phase
prolonged dietary restrictions are not
warranted.
Limitation of fluid and salt intake is
recommended in the child with oliguria or
edema.
Amounts consistent with insensible losses
help to minimize vascular overload and
hypertension.
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24. Hypertension
Blood pressure (BP) in children is classified according to
centile charts according to age, gender and height.
Hypertension in children is therefore defined as either
systolic and/or diastolic BP ≥ 95th percentile measured
on three or more separate occasions.
Antihypertensive treatment is often a combination
therapy.
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28. Anti-Hypertensive drugs
Diuretics. A diuretic (ie hydrochlorothiazide,
frusemide) may be used initially.
Later it can be combined with a ß-blockers or any
other antihypertensive drug
Beta blockers (Metopronol, propranolol), .
These medications reduce the workload of the child's
heart, causing it to beat slower and with less force.
Angiotensin-converting enzyme (ACE)
inhibitors (Captopril). These medications help
relax the child's blood vessels
Calcium channel blockers (Nifidepine). These
medications help relax the muscles the child’s child's
blood vessels and may slow the heart rate.
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29. Treatment of hypertension
Mild-to-moderate hypertension is treated most
effectively with
◦ bed rest,
◦ fluid restriction
The use of diuretics, such as Furosemide (1-2mg/kg/d
oral [PO], administered 1-2 times daily), may hasten
resolution of the hypertension.
Propranolol or newer ß-blocker
ACE inhibitors are effective, but usually are not first-
line drugs in acute glomerulonephritis (may cause
hyperkaliemia).
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30. Propranolol
Propranolol is a non-selective beta-adrenergic receptor
blocking agent.
Contraindications: Bronchospasm, including bronchial
asthma; allergic rhinitis during the pollen season; sinus
bradycardia and greater than first degree block; cardiogenic
shock; right ventricular failure secondary to pulmonary
hypertension; congestive heart failure (see Warnings) unless
the failure is secondary to a tachyarrhythmia treatable with
propranolol.
Warnings: Cardiac Failure:
Dosage:
Initial: 0.5 to 1 mg/kg/day in divided doses every 6 to 12 hours;
increase gradually every 5 to 7 days ,
Usual dose: 1 to 5 mg/kg/day
Maximum dose: 320 mg or 8 mg/kg/d
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31. Furosemide (Lasix)
Loop diuretic useful in patients with AGN who
are edematous. Has some BP-lowering effect.
In acute hypertensive states, administer IV
furosemide.
Increases excretion of salt and water by
interfering with chloride-binding cotransport
system in ascending loop of Henle.
Interactions: auditory toxicity appears to be
increased with coadministration of
aminoglycosides
Contraindications: Documented
hypersensitivity; hepatic coma; anuria; state of
severe electrolyte depletion
Pediatric dosing
◦ 1-2 mg/kg/dose PO,
◦ do not administer more frequently than q6h;
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32. Treatment of hypertension
Severe hypertension without
encephalopathy can be treated by
administration of vasodilator drugs:
◦ Hydralazine or Nifedipine.
They can be given either by injection or by
mouth
The dose can be repeated every 10-20
minutes until a suitable response is obtained.
For most children, the need for more than 2-
3 doses is unusual.
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33. Hydralazine (Apresoline)
Decreases systemic resistance through direct
vasodilation of arterioles.
Interactions: MAOIs and beta-blockers may increase
toxicity
Contraindications: Documented hypersensitivity;
mitral valve rheumatic heart disease
Pediatric dosing
◦ Acute hypertension: 0.15-0.2 mg/kg/dose PO/IM q10-20 min
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34. Nifedipine (Adalat, Procardia)
Relaxes coronary smooth muscle and produces coronary
vasodilation, which, in turn, improves myocardial oxygen
delivery.
Interactions: Caution with coadministration of any
agent that can lower BP, including beta-blockers and
opioids; H2 blockers (cimetidine) may increase toxicity
Contraindications: Documented hypersensitivity
Pediatric dosing
◦ Acute hypertension: 0.05-0.1 mg/kg/dose PO/SL q10-20min,
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35. Treatment of hypertension
1. Severe hypertension, or that associated with
signs of cerebral dysfunction, demands
immediate attention:
Labetalol , an alpha and ß-blocker, IV
Diazoxide: a potassium channel activator,
Nitroprusside , a strong muscle relaxant of
blood vessels is used in patients with severe
hypertension that is refractory to the previous
agents
Simultaneous IV administration of Frusemide
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37. Diazoxide (Hyperstat)
Indicated for emergency reduction of severe
hypertension only.
Only administer IV.
Causes local relaxation in smooth muscle by
increasing membrane permeability to
potassium ions.which decreases BP.
Pediatric dosing
◦ 2-3 mg/kg IV administered over 30 min; may
repeat in 30-60 min
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38. Nitroprusside (Nitropress)
Produces vasodilation and increases inotropic activity
of heart.
Contraindications: Documented hypersensitivity;
subaortic stenosis; idiopathic hypertrophic and atrial
fibrillation or flutter
Adult and Pediatric
◦ Begin infusion at 0.3-0.5 mcg/kg/min IV and titrate
upward by increments of 0.5 mcg/kg/min; titrate to
desired effect; Maximum 2mcg/kg/min.
Infusion rates >2 mcg/kg/min may lead to cyanide
toxicity
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39. Failure of expected resolution of clinic
signs
◦ Gross hematuria within the preceding 10-14
days
◦ Microscopic hematuria within 1 year
◦ Edema within 2 weeks
◦ Proteinuria (>50 mg/dL) within 6 months
◦ Azotemia within 1 week
◦ Hypertension within 6 weeks
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41. Prognosis
The prognosis is favorable for approximately
95% of children with sporadic
poststreptococcal acute glomerulonephritis.
The prognosis for persons with acute
glomerulonephritis secondary to other
causes is less certain.
In an extremely small proportion of patients,
the initial injury is so severe that either
persistent renal failure or progression to
renal failure occurs.
Second episodes of acute glomerulonephritis
are uncommon.
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