ACUTE GLOMERULONEPHRITIS

(AGN)

By
MOHD ZAMIR GHOUSE
060100848

FAKULTAS KEDOKTERAN
UNIVERSITAS SUMATERA UTARA
MEDAN
2010
 ACKNOWLEDGEMENT

First of all I would like to say Alhamdullillah for being able to complete this case
report in time and for all the courage and the blessings God has given me throughout this
pediactric posting which was a great deal of challenge for me. However with the help of my
supportive and understanding groupmates and also the moral support given by my parents,
I was able to handle the tremendous pressure and expectations of being a medical student
posted in the paediatric ward.

I would like to express my greatest gratitude towards my University lecturers who

tirelessly teaching and giving guidance to me in spite of coming all the way from Indonesia.
To all the staff in Paediatric ward especially the specialists of HTF, I wish I could repay the
endless efforts and sacrifices of their own time into teaching and giving us guidance
throughout the entire time in paediatric ward. Their knowledge and wisdom helped me a lot
in finishing this report. I would also like to say my special thanks to Dr. Ali who always have
the enthusiasm and patience to teach and share his knowledge with us. Lastly of course,
there wouldn’t be doctors without patients. In the paediatric ward, I was blessed to have
such a wonderful set of patients in a way that they are always willing to be clerked and
examined upon. I am very thankful and will always remember them as they are also my
teacher in another way.

In this report I will talk about a 6 year old chinese boy who came with a chief
complaint of dark colored urine for the past one day. Based on his clinical presentation and
laboratory findings, he is diagnosed with having Acute Glomerulonephritis (AGN). After 2
days in the ward he was then discharged and follow up will be done in the outpatient setting
for this child.
November 2010
Hospital Tuanku Fauziah
Kangar, Perlis

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 CONTENTS

NO. TITLE PAGE

1. Acknowledgement 2
2. Contents 3
3. Acute Glomerulonephritis
- Introduction
- Definition
- Pathophysiology
- Epidemiology
- Etiology
- Diagnosis
- Differential Diagnosis
- Management
- Prognosis
4. Case Report
5. Discussion
6. References

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 ACUTE GLOMERULONEPHRITIS

Introduction

Our blood carries oxygen and nutrients to our organs and tissues, and carries waste
products to be flushed out of our body. Our kidneys control this process. The tiny structures
that do the work in our kidneys are called nephrons. Each of our kidneys contains about one
million nephrons. Each nephron has a small blood vessel that brings in unfiltered blood, a
Glomerulus that filters the blood, a tubule that caries away filtered waste materials in the
urine, and a small blood vessel that returns filtered blood to the body.

Cross section of the human kidney

A glomerulus is a capillary tuft that performs the first step in filtering blood to form
urine. It is surrounded by Bowman's capsule in nephrons of the vertebrate kidney. It
receives its blood supply from an afferent arteriole of the renal circulation. Unlike most
other capillary beds, the glomerulus drains into an efferent arteriole rather than a venule.
The resistance of the arterioles results in high pressure in the glomerulus, aiding the process
of ultrafiltration, where fluids and soluble materials in the blood are forced out of the

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capillaries and into Bowman's capsule. A glomerulus and its surrounding Bowman's capsule
constitute a renal corpuscle, the basic filtration unit of the kidney. The rate at which blood is
filtered through all of the glomeruli, and thus the measure of the overall renal function, is
the glomerular filtration rate (GFR).

Microscopic view of the glomerulus

If a substance can pass through the endothelial cells, glomerular basement membrane, and
podocytes, then it is known as glomerular filtrate, and it enters lumen of proximal tubule.
Otherwise, it returns through the efferent circulation.

The endothelial cells of the glomerulus contain numerous pores (fenestrae) that, unlike
those of other fenestrated capillaries, are not spanned by diaphragms. The cells have
fenestrations that are 70 to 90 nm in diameter. Hence most proteins cannot pass through
except smaller ones like albumin.

The glomerular endothelium sits on a very thick (250-350 nm) glomerular basement
membrane. Not only is it uncharacteristically thick compared to most other basement
membranes (40-60 nm) but it is also rich in negatively charged glycosaminoglycans such as
heparan sulfate. The negatively-charged basement membrane repels negatively-charged
proteins from the blood, helping to prevent their passage into Bowman's space

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Podocytes line the other side of the glomerular basement membrane and form part of the
lining of Bowman's space. Podocytes form a tight interdigitating network of foot processes
(pedicels) that control the filtration of proteins from the capillary lumen into Bowman's
space. The space between adjacent podocyte foot processes is spanned by a slit diaphragm
formed by several proteins including podocin and nephrin. In addition, foot processes have
a negatively-charged coat (glycocalyx) that limits the filtration of negatively-charged
molecules, such as serum albumin. The podocytes are sometimes considered the "visceral
layer of Bowman's capsule", rather than part of the glomerulus.

Structural layers of the glomerulus

Diseases that injure glomeruli (plural for glomerulus) are called glomerular diseases.
Laboratory analysis of the urine from people who have glomerular disease often shows
protein in the urine (proteinuria) and blood in the urine (haematuria).

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 Structural damage to the layers of glomerulus

Any disease of the glomeruli must be considered serious because it interferes with the basic
functions of the kidneys; that is, filtration of liquids and excretion of waste products.

Definition

Acute glomerulonephritis (AGN) is a disease characterized by the sudden appearance

of edema, hematuria, proteinuria, and hypertension. It is a representative disease of acute
nephritic syndrome in which inflammation of the glomerulus is manifested by proliferation
of cellular elements secondary to an immunological mechanism.

Acute poststreptococcal glomerulonephritis (APSGN) results from infection by

nephritogenic streptococci. Acute poststreptococcal glomerulonephritis is now known to
follow infection by group A beta hemolytic streptococci. The M and T proteins in the
bacterial wall have been used for characterizing streptococci; M types 1, 2, 4, 12, 18, 25, 49,
55, 57, and 60 may have nephritogenic potential. These may cause skin or throat infections,
but specific M types, such as 49, 55, 57, and 60, are most commonly associated with skin
infections.

Pathophysiology

Most forms of acute poststreptococcal glomerulonephritis are mediated by an

immunologic process. Both cellular and humoral immunity is important in the pathogenesis
of acute poststreptococcal glomerulonephritis. Humoral immunity in acute
poststreptococcal glomerulonephritis is presumed to be mediated by the in situ formation
of nephritogenic streptococcal antigen-antibody complexes and circulating immune
complexes . The most widely proposed mechanism for the development of acute
poststreptococcal glomerulonephritis is that nephritogenic streptococci produce proteins
with unique antigenic determinants. These antigenic determinants have a particular affinity
for sites within the normal glomerulus.

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 Following release into the circulation, these antigens bind to these sites within the
glomerulus. Once bound to the glomerulus, they activate complement directly by
interaction with properdin. Glomerular-bound streptococcal antibodies also serve as fixed
antigens and bind to circulating antistreptococcal antibodies forming immune complexes.
Complement fixation via the classical pathway leads to generation of additional
inflammatory mediators and recruitment of inflammatory cells.

Bound plasmin can cause tissue destruction by direct action on the glomerular
basement membrane or by indirect activation of procollagenases and other matrix metalo-
proteinases. NAPlr can also activate the alternate complement pathway, leading to
accumulation of polymorphonuclear cells and macrophages and local inflammation. Also,
the in situ–formed and circulating immune complexes can readily pass through the altered
glomerular basement membrane and accumulate on the subepithelial space as humps.

A schematic representation of the proposed mechanism for acute poststreptococcal

glomerulonephritis (APSGN). C = Activated complement; Pl = Plasmin; NAPlr = Nephritis-
associated plasmin receptor; SK = Streptokinase; CIC = Circulating immune complex.

In most patients with moderate-to-severe AGN, a 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.

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Epidemiology

The disease is more frequent in children aged of 2-12 years. However, in most large series,
5-10% of patients are older than 40 years, and 5% are younger than 2 years. Although a
male dominance is noted in symptomatic cases, when subclinical and clinical disease is
taken into account, the rates are the same in males and females.

Etiology

Acute poststreptococcal glomerulonephritis follows infection of the throat or skin by certain

"nephritogenic" strains of group A β-hemolytic streptococci. The factors that allow only
certain strains of streptococci to be nephritogenic remain unclear. Poststreptococcal
glomerulonephritis commonly follows streptococcal pharyngitis during cold weather months
and streptococcal skin infections or pyoderma during warm weather months. Although
epidemics of nephritis have been described in association with both throat (serotype 12)
and skin (serotype 49) infections, this disease is most commonly sporadic.

Diagnosis

i. History & Clinical Manifestation

ii. Laboratory Studies
iii. Imaging Studies
iv. Procedures

i. History & Clinical Manisfestation

Most patients with acute glomerulonephritis (AGN) exhibit milder symptoms and/or signs
somewhere between the extremes described below :

- At one extreme is the 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 acute poststreptococcal

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 glomerulonephritis (APSGN), at least 50% of persons with laboratory evidence of
nephritis (ie, abnormal urinalysis) appear to have no symptoms or signs of clinical
illness.
- At the other extreme is the child who presents with severe disease manifested by
oliguria, edema, hypertension, and azotemia and with proteinuria, hematuria, and
urinary casts (cylindruria).

In those patients whose acute glomerulonephritis is the result of a postinfectious cause (ie,
poststreptococcal acute glomerulonephritis being the most common), a latent period of 7-
21 days between onset of the streptococcal infection and development of clinical
glomerulonephritis is characteristic. This latent period, more clearly defined after
pharyngeal infections than after pyoderma, averages approximately 10 days. The
development of clinical nephritis (ie, hematuria and/or edema) either during or within 2-5
days after the onset of a respiratory tract infection is atypical and suggests the possibility of
some other form of glomerulonephritis.

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. Observant parents may
also note oliguria.

An insidious onset of edema is more indicative of other forms of renal disease.

An occasional child may have a scarlatiniform rash or evidence of a viral exanthema, but
petechial or purpuric rashes suggest other conditions. Almost characteristic by their absence
are arthralgia, arthritis, carditis, hepatic involvement, and GI bleeding.

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 and
depends on a number of factors, including the severity of glomerular involvement, the fluid
intake, and the degree of hypoalbuminemia.

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Gross hematuria occurs at onset in 30-50% of children with poststreptococcal acute
glomerulonephritis who require hospitalization. The urine is usually described as being
smoky, cola colored, tea colored, or rusty. The color is usually dependent on the amount of
blood present and the pH of the urine. Observant parents may note oliguria. Clots are
exceedingly rare in persons with acute glomerulonephritis.

Hypertension is the third cardinal feature of poststreptococcal acute glomerulonephritis and

is reported in 50-90% of children who are hospitalized with acute glomerulonephritis. The
pathogenesis of the hypertension is unknown; however, pathogenesis is probably
multifactorial and related only in part to extracellular fluid (ECF) volume expansion. The
magnitude of the increase in blood pressure (BP) widely varies; however, systolic pressures
greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg are not unusual.
Hypertensive encephalopathy has been reported in approximately 5% of hospitalized
children and is the most serious early complication of this disease. In these patients,
hypertension is usually severe and is accompanied by signs of CNS dysfunction such as
headache, vomiting, depressed sensorium, confusion, visual disturbances, aphasia, memory
loss, coma, and convulsions. Hypertensive encephalopathy has been reported in the
occasional individual with minimal or no edema and with minimal urinary abnormalities.

Circulatory congestion is apparent in most children admitted to the hospital but is

responsible only rarely for significant early symptoms. 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 until onset of
diuresis In the patient with an otherwise normal cardiovascular system, cardiac failure is
unusual. Pallor is common at onset and is not explained entirely by the anemia.

ii. Laboratory Studies

•Urine

Urine output most is often reduced in acute glomerulonephritis (AGN), and urine is
concentrated and acidic. Glucosuria occurs occasionally, and proteinuria is commonly
present. The urine reaction for protein rarely exceeds 3+ by dipstick, corresponding to fewer

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than 2 g/m2/d when assessed quantitatively. Approximately 2-5% of children with acute
poststreptococcal glomerulonephritis (APSGN) have massive proteinuria and a nephrotic
picture. Hematuria is the most consistent urinary abnormality, although histologic findings
consistent with poststreptococcal acute glomerulonephritis have been reported in children
who had no or minimal urinary abnormalities. Polymorphonuclear leukocytes and renal
epithelial cells are common in the urine of patients with poststreptococcal acute
glomerulonephritis, particularly during the early phase of the disease. Hyaline and/or
cellular casts are almost always present. RBC casts have been found in 60-85% of
hospitalized children with poststreptococcal acute glomerulonephritis. RBC casts, although
characteristic of a glomerular lesion, are often not detected because the urine is not fresh or
is examined by an inexperienced person.

•Streptococcal infection

Look for evidence of streptococcal infection in all patients. Cultures from either the pharynx
or skin may be positive; however, high streptococcal antibody titers are more compelling.
Numerous laboratory tests can be used to measure antibodies to various streptococcal
antigens (eg, ASO, AH, anti-DNase B) or to combinations of antigens (eg, streptozyme test).
Whatever test is used, a rise in the titer of the antibody, measured at an interval of 2-3
weeks, is more meaningful than a single measurement. An ASO titer of 250 U or higher is
highly suggestive of recent streptococcal infection.

•Hemolytic complement

Total hemolytic complement and some of its components are low during poststreptococcal
acute glomerulonephritis. The concentration of C3 has been found to be decreased in more
than 90% of patients with poststreptococcal acute glomerulonephritis when measured
serially during the first 2 weeks of the illness. Total hemolytic complement values are also
depressed. These tests help to differentiate poststreptococcal from other postinfectious
forms of acute glomerulonephritis. C4 levels are most often normal. Serum levels of fifth
component of complement (C5) and properdin are usually decreased. The complement
levels generally return to normal by 6-8 weeks after onset.

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•Renal

The extent of renal functional impairment is correlated directly to the severity of the
glomerular injury. The elevation in the serum concentrations of creatinine and BUN is
usually modest, although some patients may have severe azotemia at onset. The electrolyte
profile is usually normal; hyperkalemia and metabolic acidosis are only present in patients
with significant renal functional impairment. The same applies to hyperphosphatemia. Total
serum calcium, but not ionized calcium levels, may be low in patients who have a nephrotic
picture.

•Blood

A mild anemia (normocytic, normochromic) is common in persons in the early phase of

acute glomerulonephritis; its degree tends to parallel the degree of extracellular (ECF)
volume expansion. Erythropoiesis may decline in the aftermath of acute glomerulonephritis,
particularly in individuals with severe cases. WBC and platelet counts are usually normal,
although an occasional patient exhibits a leukocytosis; rarely, a mild thrombocytopenia may
be present. A few patients have hypoproteinemia and hyperlipidemia. A nephrotic picture
has been reported in approximately 5% of hospitalized patients with poststreptococcal
acute glomerulonephritis.

iii. Imaging Studies

No specific radiologic studies are particularly helpful in either the evaluation or the
treatment of patients with acute glomerulonephritis. Renal ultrasonography generally
demonstrates normal to slightly enlarged kidneys bilaterally with some evidence of
increased echogenicity. Chest radiographs commonly demonstrate central venous
congestion in a hilar pattern, the degree of which parallels the increase in ECF volume.
Occasionally, an enlarged cardiac shadow is evident.

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 iv. Procedures

No procedures are recommended routinely in the evaluation of patients with acute

glomerulonephritis. The performance of a renal biopsy is indicated in patients whose clinical
presentation, laboratory findings, or course is atypical. In such persons, study of the
histology by light, immunofluorescent, and electron microscopy may be diagnostic.

Differential diagnosis

Other postinfectious causes of acute glomerulonephritis (AGN) must be considered in the

differential diagnosis of acute poststreptococcal glomerulonephritis (APGN) because the
syndrome of AGN has been reported following many other bacterial illnesses (eg,
Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Rickettsia
rickettsiae, Mycoplasma species, Meningococcus species, Leptospira species). In addition,
certain viral illnesses have preceded the onset of fairly typical AGN; among the most
common are varicella-zoster virus, cytomegalovirus, and the Epstein-Barr virus. In the
evaluation of a patient with AGN, if evidence of a prior streptococcal infection is missing or
inconclusive, then a search for another infectious cause appears appropriate.

The differential diagnosis of acute glomerulonephritis can be divided as follows

(percentages indicate approximate frequency of C3 or hemolytic complement):

1) Low serum complement level

 Systemic diseases
- SLE (focal, 75%; diffuse, 90%)
- Subacute bacterial endocarditis (90%)
- Visceral abscess
- "Shunt" nephritis (90%)
- Cryoglobulinemia (58%)
 Renal diseases
- Acute postinfectious glomerulonephritis (>90%)
- MPGN - Type I (50-80%), type 2 (80-90%)

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 2) Normal serum complement level
 Systemic diseases
- Polyarteritis nodosa group
- Hypersensitivity vasculitis
- Wegener granulomatosis
- HSP
- Goodpasture syndrome
 Renal diseases
- IgA (or IgG-IgA) nephropathy
- Idiopathic rapidly progressive glomerulonephritis (RPGN)
- Anti-glomerular basement membrane (GBM) disease
- Negative immunofluorescence findings
- Immune complex disease

Management

a) Medical care
b) Diet

Medical care

General management begins with a decision to admit the child with acute
glomerulonephritis (AGN) to the hospital or merely have him or her undergo frequent
outpatient examinations. Hospitalization is indicated if the child has significant hypertension
or a combination of oliguria, generalized edema, and elevation of serum creatinine or
potassium.

Treatment of hypertension is necessary escpecially if there is evidence of cerebral

dysfunction marked by severe hypertension. Some of the drugs that are used in treating
severe hypertension are :

- Labetalol (0.5-2mg/kg/hr IV)

- Nitroprusside (0.5-2mcg/kg/min IV)

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Severe hypertension without encephalopathy can be treated in the manner above or more
commonly by administration of vasodilator drugs such as hydralazine or nifedipine. Mild to
moderate hypertension does not warrant any emergency treatment, they are usually
treated most effectively with bed rest and fluid restriction. The use of loop diuretics such as
furosemide (1-3mg/kg/d PO) administered twice daily may hasten resolution of the
hypertension.

The oedema 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. Loop diuretics
administered PO have been reported to reduce the length of hospitalization in children who
are oedematous.

A course of penicillin can be administered to avoid contamination of contacts with a

nephritogenic strain of streptococci; however, in most instances, these contacts do not
develop overt acute glomerulonephritis. Such therapy does not influence the course of the
disease in the index patient, but it may alter the response that confers type-specific
immunity. Throat cultures of immediate family members might detect patients who are
asymptomatic but infected. Antibiotics is administered for 10 days to ensure eradication of
streptococci, if the disease is believed to be poststreptococcal acute glomerulonephritis and
risk of contamination is present. Penicillin <12 years 25-50mg/kg/d PO divided into tds or
qid dose, >12 years 250-500mg PO 6-8hrs daily for 10 days.

Diet

A low-sodium, low-protein diet should be prescribed during the acute phase, when edema
and hypertension are in evidence; however, prolonged dietary restrictions are not
warranted. Limitation of fluid and salt intake is recommended in the child who has either
oliguria or edema. Curtailment of fluid to amounts consistent with insensible losses helps to
minimize vascular overload and hypertension

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Prognosis

Complete recovery occurs in more than 95% of children with acute poststreptococcal
glomerulonephritis. Mortality in the acute stage can be avoided by appropriate
management of acute renal failure, cardiac failure, and hypertension. Infrequently, the
acute phase may be severe and lead to glomerular hyalinization and chronic renal
insufficiency. However, the diagnosis of acute poststreptococcal glomerulonephritis must be
questioned in patients with chronic renal dysfunction because other diagnoses such as
membranoproliferative glomerulonephritis may be present. Recurrences are extremely rare.

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