West Visayas State University – College of Medicine – Batch 2020

Block XIX
Module 3 Glomerulonephritides in Children
Lecture 5
03/ 12/ 19
Lynette Fillone-Alcala, MD, FPPS, FPSN, FPNSP

TOPIC OUTLINE Urinalysis revealed proteinuria (++++), 3-5 RBCs/hpf,

I. Cases
II. Acute Nephritic Syndrome
A. Acute Post-Streptococcal Glomerulonephritis
III. Acute Nephrotic Syndrome
B. Idiopathic Nephrotic Syndrome
IV. Supplementary Notes
Review Questions
References
Appendix
LECTURER BOOK REFERENCE OLD TRANS
CASE
Case No. 1
ANA, a 10-year-old female child was brought to the OPD
for consult.
2 weeks PTC, she had symptoms of URTI, associated
with throat pain, fever, and nasal congestion
1 day PTC, puffy eyelids were noted upon waking up in
the morning, with associated headache and vomiting of
previously taken in breakfast.
Prior to leaving home, she had one episode of grossly
red urine. What is your primary impression?
Ans: Acute Post-Streptococcal Glomerulonephritis
The edema of nephritic syndrome is typically most
prominent early in the morning
Case No. 2
An 18-year-old female, single, adolescent with OB score
of G1P0, & 23 weeks pregnant was referred by the
OB-GYNE service due to persistent abdominal pain
and hematuria
PE revealed alopecia, fine maculopapular rashes in the
auricular area, & swelling of the left ankle joint.
CBC revealed anemia with mild thrombocytopenia.
Urinalysis revealed a urine specific gravity of 1.015,
hazy reddish urine with packed filled RBC, pus cells of
3-5/hpf, negative sugar, & (++) proteins. What is your
strongest consideration?
Ans: Lupus Nephritis
Pregnancy is an exacerbating factor for lupus
Case No. 3
Mark, an 8-year-old male was brought to the ER for
facial puffiness of 1-week duration, which progressed
to abdominal distention & anasarca
PE revealed a HR of 80bpm, RR of 20 cpm, BP of 90/60
mmHg.
and a urine specific gravity of 1.015. What is your
primary impression of Mark’s case?
Ans: Acute Nephrotic Syndrome
Hemolytic uremic syndrome (HUS) commonly affects
young children and typically presents with
gastroenteritis as a prodrome
INTENDED LEARNING OBJECTIVES
1. Recognize the clinical presentation of a child
presenting with acute nephritic syndrome
2. Differentiate acute nephritic syndrome from acute
nephrotic syndrome
3. Discuss acute post-streptococcal glomerulonephritis
as the pathognomonic acute nephritic syndrome in
children
4. Discuss idiopathic nephrotic syndrome as the
pathognomonic acute nephrotic syndrome in
children
5. Recognize other common nephritides in the pediatric
age group
I. ACUTE NEPHRITIC SYNDROME
CLINICAL CRITERIA
1. Edema
The edema of nephritic syndrome can be severe
enough to cause dyspnea, shortness of breath or
even respiratory compromise
The edema of nephritic syndrome is most
prominent in the morning, and on the patient’s
dependent side, but gradually recedes as the day
progresses
2. Hypertension
The hypertension of nephritic syndrome may be
severe enough to cause hypertensive
encephalopathy, seizures, and even status
epilepticus
The hypertension of nephritic syndrome is
primarily due to fluid retention. This is in contrast
with nephrotic syndrome where the intravascular
volume is depleted due to the third-spacing brought
about by hypoalbuminemia
3. Hematuria
The most common reason for consult, but is also
the most benign among the clinical criteria. It may be
microscopic or gross
4. Oliguria
Oliguria may progress to renal failure, especially
if the patient wasn’t dialyzed at the right time. If this
occurs, the child may have to be placed on chronic

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MD 3 Jose, Elson, Kristian, Bryan
 replacement therapy or may even die due to
complications
Parents and caregivers may not notice this
manifestation because of how slowly it develops
CAUSES
1. Isolated Renal Disease
• IgA nephropathy
• Alport syndrome (hereditary nephritis)
• Thin glomerular basement membrane nephropathy
• Post-infectious GN (post-strep)
• Membranous nephropathy
• Membranoproliferative GN
• Focal segmental glomerulosclerosis (FSGS)
• Antiglomerular basement membrane disease
IgA nephropathy is the leading cause of
glomerulonephritis secondary to an isolated renal
disease However, post-infectious (or post-strep)
glomerulonephritis is the most common cause in our
locality
Membranous nephropathy is typically a disease of
adults
Membranoproliferative GN is an autoimmune disease
that typically follows an infection and so may be
misdiagnosed as post-strep GN; it should be
suspected when the manifestations of the patient
does not follow the typical course of a post-strep GN
and can be confirmed via biopsy
FSGS is the worst diagnosis among the following and
may also cause nephrotic syndrome
2. Multisystem Diseases
• Systemic lupus erythematosus with nephritis
• Henoch-Schonlein purpura with nephritis
• Wegener granulomatosis
• Polyarteritis nodosa (PAN)
• Goodpasture syndrome
• Hemolytic uremic syndrome (HUS)
• Sickle cell glomerulopathy
• HIV nephropathy
The typical picture of HUS is hematuria and
abdominal pain, with GI symptoms as a prodrome. It
may be differentiated from SLE through the type of
rash presented and the presence of elevated BUN &
creatinine levels
Sickle cell glomerulopathy is seldom seen in the
Philippines
HIV nephropathy is a new entity & cases are currently
rising
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Figure 1. Common Biopsy Findings in Children. Source: Journal of the
Korean Society of Pediatric Nephrology (2017)
1. Recurrent macroscopic hematuria (35.8%)
2. Nephrotic syndrome associated with hematuria or
HTN (10.7%)
3. Persistent microscopic hematuria with proteinuria
(10.1%)
4. Steroid-resistant, steroid-dependent, or frequent-
relapsed nephrotic syndrome (10.1%)
5. Evaluation of renal involvement in systemic disease
(8.5%)
6. Persistent microscopic hematuria (7.2%)
7. Others (17.6%)
ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS (APSGN)
• A classic example of acute nephritic syndrome
• Characterized by a sudden onset of gross hematuria,
edema, hypertension, and renal insufficiency
• The most common cause of GN in our locality, but is
surpassed by IgA nephropathy worldwide
• Also the most common glomerular cause of gross
hematuria in children
• Follows infection of the throat or skin by certain
nephritogenic strains of Group A β-hemolytic
streptococci
Trends show that in the Philippines, IgA nephropathy
cases are closing in as the most common cause of
nephritic syndrome because cases of sore throat are
now detected earlier and treated with antibiotics
earlier, preventing their progression to PSGN
Dr. Alcala urged us to read on the characteristics of
Group A β-hemolytic streptococci
PATHOLOGY
• Kidneys appear symmetrically enlarged & affected
because of the autoimmune mechanism of PSGN
• All glomeruli appear enlarged & relatively bloodless
with mesangial cell proliferation & an increase in
mesangial matrix
• PMN leukocytes are commonly seen in the glomeruli
during the early stages of the disease
• Crescents and interstitial inflammation may be seen in
severe and rapidly progressive cases
• Immunofluorescent microscopy reveals lumpy-bumpy
deposits of Ig & complement in the glomerular
basement membrane (GBM)
• Electron microscopy (EM) reveals electron-dense
deposits or “humps”
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Figure 2. The Glomerulus as seen in PSGN
PATHOGENESIS
The Immune Complex Theory
• Glomerular deposition of nephritogenic streptococcal
antigens & subsequent formation of immune
complexes in situ and/or the deposition of circulating
antigen-antibody complexes (Oda et al., 2010)
• Antigens considered potential causes of APSGN
Nephritis-associated plasmin receptor (NAPlr)-
streptococcal glyceraldehyde-3-phosphate
dehydrogenase
Cationic cysteine proteinase-streptococcal
pyogenic exotoxin B (SPEB)
Educate children with APSGN regarding what
happened to their kidneys. This is the best way to
promote compliance to a low-salt diet (esp. one
without fast food)
Dr. Alcala also gives McDonald’s to patients with
APSGN after 6-12 weeks of management as a price
and to identify patients that were misdiagnosed as
APSGN. If manifestations are triggered after 6-12
weeks, then suspect a different diagnosis
CLINICAL MANIFESTATIONS
• Most common in children 5-12 years old
• Uncommon before the age of 3 years
• Typical patients develop acute nephritic syndrome 1-
2 weeks after a streptococcal pharyngitis or 3-6
weeks after a streptococcal pyodermata
• Symptoms vary from asymptomatic hematuria to
acute renal failure, as well as varying degrees of
hypertension, edema, & oliguria (<1 cc/kg/hr)
Though rare, APSGN should still be suspected in
patients 3 to 18 years old
Look for healed skin lesions in the extremities
Cases of APSGN that are referred late should be
dialyzed
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Some patients, however, even those with anuria for
~24 hours, creatinine levels of 300-500, & elevated
potassium levels may improve dramatically after 2-3
sessions of chemo (?) or a 1-week course of
peritoneal dialysis
Some cases of nephritic syndrome present with a
very rapid course, and are called rapidly
progressive glomerulonephritis. This warrants
immediate prednisolone therapy and a course of
peritoneal dialysis to decrease creatinine levels, and
help in the excretion of toxins and potassium. In
these cases, the edema and hypertension should
also be controlled and some patients may present
with seizures due to either uremic encephalopathy, or
hypertensive encephalitis
PHASES
Phase 1: Oliguric
• Edema, hypertension, & oliguria
Edema is due to salt & water retention
• Non-specific symptoms such as lethargy, abdominal
or flank pain, & fever are also common
• Nephrotic syndrome may also develop in 10-20% of
cases
• This acute phase generally resolves within 6-8 weeks
A low-salt diet and fluid volume restriction (based on
body surface area & daily output) can be given as
adjunct management
Hypertension should be suspected if the patient
presents with vomiting, dizziness, or headache
A Foley catheter may be inserted to properly assess
renal output. An adequate urine output is at least 1
cc/kg/hr
Other factors to investigate include the duration from
last urine output, volume, color, and character of the
urine
Phase 2: Diuretic
• Edema resolves, & diuresis ensues
• Dehydration & electrolyte imbalances should be
monitored
Closely monitor sodium levels which are closely
related with hydration status and also for
hypokalemia, especially in those taking loop diuretics
Phase 3: Convalescence
Returns to normal but you have to manage the
diuretic phase since in some cases patients go back
already having severe dehydration
DIAGNOSIS
• Urinalysis: (+) RBC, RBC casts, proteinuria, & PMNs
• Mild normocytic anemia may be present due to
hemodilution and low-grade hemolysis
• C3 level is usually reduced
• (+) Throat culture for streptococci
• ASO titer (to diagnose recent infection)
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 • Anti-deoxyribonuclease (Dnase) B levels
• (+) Streptozyme test
• Clinical diagnosis is likely in a child with acute
nephritic syndrome, evidence of recent strep
infection, & low C3 level
• Renal biopsy is considered only if with acute renal
failure, nephrotic syndrome, absence of evidence of
strep infection, & normal complement levels OR
persistent hematuria/proteinura, diminished renal
function & low C3 levels for >2 months
C3 levels are typically decreased because they get
deposited in the glomerular basement membrane
(GBM), except in rapidly progressive cases where it
is elevated
Other causes of GN & low C3 levels include SLE,
and valvular lesions/shunt nephritis
ASO titers are commonly elevated after pharyngeal
infections, but rarely after streptococcal skin
infections
Streptozyme tests are more specific than ASO titers,
but ASO is usually enough for diagnosis
Other conditions should be considered if
manifestations are markedly prolonged
C4 is often normal or only mildly depressed
Confirmation of dx requires evidence of prior strep
infection
The anti-DNase B level is the best antibody titer to
document cutaneous streptococcal infections
MRI is indicated for patients with neurologic
symptoms and results may show reversible posterior
leukoencephalopathy in the parieto-occipital areas on
T2-weighted images
Chest X-rays are indicated in those with signs of
heart failure or respiratory distress
COMPLICATIONS
• Hypertension (60%)
Hypertensive encephalopathy (10%)
─ Hypertensive encephalopathy may manifest
with a coma, stroke, or even cortical blindness
• Acute renal dysfunction
• Heart failure
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Acidosis
• Seizures
• Uremia
TREATMENT
• Penicillin – Drug of choice
10 day course of systemic antibiotics is
recommended to limit the spread of nephritogenic
pathogens
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• Sodium restriction
• Diuresis with IV furosemide
• Calcium channel antagonists, vasodilators, or ACE
inhibitors for hypertension
Diuretics are the 1st line drugs for HTN, even though
some say CCBs are the safest in children
Use caution with ACE inhibitors and ARBs as they
may worsen renal hypoperfusion (esp. in the early
stages) and put the child at risk for further renal
failure
PROGNOSIS
• Complete recovery in 95% of children with PSGN
• Mortality is avoided by appropriate management of
acute renal failure, cardiac failure, & HTN
• Infrequently, the acute phase may be severe enough
to cause glomerular hyalinization and CKD
• Recurrences are extremely rare
PREVENTION
• Use of early systemic antibiotics for strep throat and
skin infections does not eliminate risk for PSGN
• Family members with acute GN should be considered
at risk and be cultured for Group A β-hemolytic
streptococci, and treated, if appropriate
• Family pets, particularly dogs, have been reported as
carriers
II. ACUTE NEPHROTIC SYNDROME
CLINICAL CRITERIA
1. Edema
The edema of nephrotic syndrome is typically
generalized (periorbital  facial  abdominal 
anasarca) and is secondary to protein loss and a
drop in oncotic pressure
2. Normal Blood Pressure
3. Proteinuria
In children, proteinuria is defined as ≥40 mg/m2
4. Hypercholesterolemia
A compensatory mechanism by the liver to
increase oncotic pressure, & does not require
treatment, unless extremely elevated (managed with
low doses of statins; off-label use)
CAUSES
A. PRIMARY (IDIOPATHIC) NEPHROTIC SYNDROME
(INS) – 90%
Approximately 90% of children with nephrotic
syndrome have INS
• It is more common in males than females (2:1) and
appears between the ages of 2-6 years old; but can
appear as early as 6 months throughout adulthood.
• It includes multiple histologic types: minimal change
disease, mesangial proliferation, focal segmental
glomerulosclerosis, membranous nephropathy, and
membranoproliferative glomerulonephritis
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• Minimal Change Disease (MNCS) – 85%
85-90% of patients <6 years old
20-30% in adolescents
• Mesangial proliferation – 5%
• Focal segmental sclerosis (FSGS) – 10%
develops in older children
suspect in a child who presents with nephrotic
syndrome later than the age of 6 or those who are
diagnosed with nephrotic syndrome but are poorly
responsive to steroids or with frequently relapses
Considered to be a severe form which has a
poorer prognosis; it is hard to achieve remission in
these cases; usually edema is intractable and
dialysis starts from early childhood and continued
to adulthood.
B. SECONDARY NEPHROTIC SYNDROME – 10%
IDIOPATHIC NEPHROTIC SYNDROME (INS)
Associated with primary glomerular disease without
evidence of a specific systemic cause
PATHOPHYSIOLOGY:
• Increase in permeability of the glomerular capillary wall
leads to massive proteinuria and hypoalbuminemia
• Cause of increased permeability is not well understood
MINIMAL CHANGE DISEASE (MNCS)
• T-cell dysfunction leads to alteration of cytokines which
causes loss of negatively charged glycoproteins within
the glomerular capillary wall
Patients with MNCS are very prone to infection
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
• Plasma factor produced by lymphocytes maybe
responsible for the increase in capillary permeability
This plasma factor is the reason why even if you
transplant these patients with a new kidney, the
condition still recurs in the transplanted kidney
• Mutations in podocyte proteins: Podocin & Alpha
actinin
• 4 are associated with FSGS
• Steroid resistant nephrotic syndrome is associated with
mutations in NPHS2 (podocin) and WT1 genes
You may do diagnosis by trial: start patient on
steroid tx then note if the patient responds after 4
weeks. The patient must have control of
proteinuria; very good responders can diurese at 7-
10 days.
There is also a positive expression of WT1 gene in
Wilm’s tumor
CLINICAL MANIFESTATIONS OF INS
• Children usually present with mild edema
• Edema generalized with the development of ascites,
pleural effusion, and genital edema.
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Give albumin when there is genital edema
because it’s very painful.
When you examine the umbilicus, it would already
appear slit-like
• Misdiagnosed as an allergic disorder because of the
• Periorbital swelling that decreases throughout the day
• Anorexia, irritability, abdominal pain and diarrhea are
common.
• Hypertension and gross hematuria are uncommon
They are more commonly seen in nephritic rather
than nephrotic
DIAGNOSIS
• Urinalysis: 3+ or 4+ proteinuria
• Microscopic hematuria in 20% of children
• Spot urine: Protein/creatinine ratio exceeds 2.0
• Urinary protein excretion: exceeds 3.5g/24 hrs in adults
and 40mg/m2/hr in children
• Serum creatinine usually normal
• Serum albumin level <2.5g/dL
Effect of albumin infusion is just transient. It will
temporarily evacuate fluids from the 3rd space and
cause diuresis. As soon as the albumin is excreted in
the kidney, the albumin levels will decrease again. In
nephrotic syndrome you have to give steroid therapy.
The problem with steroid therapy is that when there is
a concomitant infection, and you give steroids, the
infection will be out of control leading to worsening of
infection.
• Serum cholesterol and triglycerides elevated
• C3 and C4 are normal
• Renal Biopsy NOT required in steroid responsive cases
When it clinical findings fit INS, renal biopsy is not
necessary; a good clinical history with a significant
urinary parameters is already enough to have a
final diagnosis
Indications in doing renal biopsy is steroid resistant
nephrotics
DIFFERENTIAL DIAGNOSIS
1. Protein-losing enteropathy
2. Hepatic Failure
3. Congestive heart failure
4. Acute/Chronic GN
5. Protein Malnutrition
TREATMENT
• MCNS
Children with onset of uncomplicated nephrotic
syndrome between 1 and 8 yr of age are likely to
have steroid-responsive MCNS, and steroid
therapy may be initiated without a diagnostic
renal biopsy.
Children with features that make MCNS less
likely (gross hematuria, hypertension, renal
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 insufficiency, hypocomplementemia, or age <1 yr
or >8 yr) should be considered for renal biopsy
before treatment.
In children with presumed MCNS, prednisone
should be administered - 60 mg/m2/day
(maximum daily dose, 80 mg) in a single daily
dose for 4-6 consecutive wk. After the initial 6-wk
course, the prednisone dose should be tapered
to 40 mg/m2/day given every other day as a
single daily dose for at least 4 wk. The alternate-
day dose is then slowly tapered and discontinued
over the next 1-2 months
• Steroid resistant: children who continue to have
proteinuria (2+ or greater) after 8 wk of steroid
therapy; and a diagnostic renal biopsy should be
performed.
Relapses should be treated with 60 mg/m2/day
(80 mg daily max) in a single am dose until the
child enters remission (urine trace or negative for
protein for consecutive days). The prednisone
dose is then change to alternate-day dosing as
noted with initial therapy, and gradually tapered
over 4-8 wk.
Prednisone still the gold standard, 60mg/m2, can
give for 6 weeks.
• Steroid dependent: relapse while on alternate day
steroid therapy or within 28 days of completing a
successful course of prednisone therapy.
• Frequent relapsers - Patients who respond well to
prednisone therapy but relapse ≥4times in a 12-mo
period.
• Steroid resistant – children who fail to respond to
prednisone therapy within 8 wk of therapy. Steroid
resistant nephrotic syndrome is usually caused by
FSGS (80%), MCNS, or mesangial proliferative
glomerulonephritis.
Alternative therapies for steroid-dependent
patients, frequent relapsers, and steroid resistant
patients: Cyclophosphamide (2 mg/kg) is given
as a single oral dose for a total duration of 8-12
wk. Alternate-day prednisone therapy is often
continued during the course of
cyclophosphamide administration. Cyclosporine
or tacrolimus are useful as steroid-sparing
agents. Mycophenolate can maintain remission in
children with steroid dependent or frequently
relapsing nephritic syndrome.
Levamisole - anthelminthic agent with
immunomodulating property
Angiotensin-converting enzyme (ACE) inhibitors
and angiotensin II blockers - adjunct therapy to
reduce proteinuria in steroid-resistant patients.
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COMPLICATIONS
A. INFECTIONS
• Children in relapse have increased susceptibility to
bacterial infections because of urinary loss of
immunoglobulins and properdin factor B
• Defective cell-mediated immunity
• Immunosupressive therapy or steroid therapy
• Malnutrition
• Edema/ascites acting as a potential culture medium
Even a light prick in the involved area may already
result in progressive phlebitis
B. SPONTANEOUS BACTERIAL PERITONITIS
• Most frequent type of infection
• Streptococcus pneumoniae is the most common
organism
• E. coli also encountered
C. SEPSIS, PNEUMONIA, CELLULITIS, UTI
If patient presents with the classic signs and
symptoms of UTI, it warrants you to request for a
urine culture.
D. THROMBOEMBOLIC EVENTS
E. CARDIOVASCULAR DISEASE
You can give FF plasma instead of albumin in cases
of albumin allergy
PROGNOSIS
• Majority of children with steroid responsive NS have
frequent relapses until they grow older
• SRNS unlikely to develop chronic kidney disease
• FSGS poorer prognosis
• Recurrent NS develop in transplant recipients with
FSGS
So far, there is no successful therapy for FSGS.
Even if you do transplant, it also tends to recur.
SECONDARY NEPHROTIC SYNDROME
Nephrotic syndrome can occur as a secondary
feature of many forms of glomerular disease.
• Membranous nephropathy, membranoproliferative
glomerulonephritis, postinfectious glomerulonephritis,
lupus nephritis, and Henoch-Schönlein purpura
nephritis can all have a nephrotic component
• Secondary nephrotic syndrome should be suspected in
patients >8 yr and those with hypertension, hematuria,
renal dysfunction, extrarenal symptoms (rash,
arthralgias, fever), or depressed serum complement
levels.
• In certain areas of the world, malaria and
schistosomiasis are the leading causes of nephrotic
syndrome. Other infectious agents associated with
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 nephrotic syndrome include hepatitis B virus, hepatitis
C virus, filaria, leprosy, and HIV
CAUSES OF SECONDARY INS GENERALLY
INCLUDE
A. INFECTIONS
B. DRUGS
• Also developed during therapy with numerous drugs
and chemicals. The histologic picture can resemble
membranous glomerulopathy (penicillamine, captopril,
gold, nonsteroidal anti-inflammatory drugs, mercury
compounds), MCNS (probenecid, ethosuximide,
methimazole, lithium), or proliferative
glomerulonephritis (procainamide, chlorpropamide,
phenytoin, trimethadione, paramethadione).
C. IMMUNOLOGIC OR ALLERGIC
D. MALIGNANCY
• Nephrotic syndrome has been associated with
malignancy, particularly in the adult population.
• Patients with solid tumors, such as carcinomas of the
lung and gastrointestinal tract, the renal pathology
often resembles membranous glomerulopathy.
• Immune complexes composed of tumor antigens and
tumor-specific antibodies presumably mediate the
renal involvement. In patients with lymphomas,
particularly Hodgkin lymphoma, the renal pathology
most often resembles MCNS. The proposed
mechanism of the nephrotic syndrome is that the
lymphoma produces a lymphokine that increases
permeability of the glomerular capillary wall. Nephrotic
syndrome can develop before or after the malignancy
is detected, resolve as the tumor regresses, and return
if the tumor recurs.
E. METABOLIC
IGA NEPHROPATHY
• Aka Berger Nephropathy
They may cross between nephritic- nephrotic
• The most common chronic glomerular disease
worldwide
In our setting, it’s still Post Strep AGN
• Characterized by predominance of IgA within
mesangial deposits of the glomerulus in the absence
of systemic disease (symptomatic systemic lupus
erythematosus or Henoch-Schönlein purpura)
• IgA is the predominant immunoglobulin deposited in
the mesangium but lesser amounts of IgG, IgM, and
C3.
C3 is normal because it is not the complement that
deposits, it is the IgA
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• Some children display generalized mesangial
proliferation that maybe associated crescent
formation and scarring
PATHOLOGY AND PATHOLOGIC DIAGNOSIS
• Diagnosis REQUIRES renal biopsy, which is performed
when clinical features warrant confirmation of the
diagnosis or characterization of the histologic severity,
which might affect therapeutic decisions
• Focal and segmental mesangial proliferation and
increased mesangial matrix are seen in the glomerulus
• Renal histology demonstrates mesangial proliferation
that may be associated with epithelial cell crescent
formation and sclerosis.
• IgA deposits in the mesangium are often accompanied
by C3 complement
• The abnormalities identified in the IgA immunoglobulin
system have also been observed in patients with
Henoch- Schönlein purpura and lends support to the
hypothesis that these two diseases are part of the
same disease spectrum.
• Genome-wide linkage analysis suggests the linkage of
IgA nephropathy to 6q22-23 in multiplex IgA
nephropathy kindreds.
CLINICAL MANIFESTATIONS
• Gross Hematuria may occur in association with upper
respiratory tract infection with loin pain
IgA Nephropathy is suspected if 2-3 days prior,
patient had URTI and manifests with gross
hematuria and the patient had similar manifestation
after onset of URTI a year prior
• Proteinuria <1000mg/24hr
• Mild/moderate hypertension in children with nephritic
syndrome
• Normal serum C3
An important differentiating factor; may already rule
out post-strep GN if C3 is normal
• 20-30% progress to Chronic Kidney Disease
TREATMENT
• Primary Treatment of IgA Nephropathy is proper
blood pressure control
Usually, mainstay of treatment is the use of ACEIs
or ARBs because it can also reduce proteinuria,
aside from lowering the BP.
• Fish oil, which contains anti-inflammatory omega-3
polyunsaturated fatty acids decrease the rate of renal
progression in adults.
• Immunosupressive therapy; alternate day
corticosteroids
cyclosporine, mycophenylate mofetil
• Angiotensin-converting enzyme or Angiotensin II
receptor antagonists are effective in reducing
proteinuria
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 Be wary because of renal insufficiency, you might Table 3. Clinical Manifestation of Glomerular Diseases.
push patient to renal failure. Source: Doc’s Lecture
• Recurrent rate is frequent in transplanted kidney Chronic GN Macroscopic Asymptomatic
Hematuria
PSAGN vs IgA Nephropathy HPN Brown/red painless Proteinuria:
• PSAGN Edema hematuria 150 mg- 3g/dL
CKD Coincides w/ infection Hematuria: 3
Infection is 2-3 wks before onset of hematuria,
Variable Asymptomatic RBC/hpf casts
edema
proteinuria hematuria/proteinuria
You have a window period with no symptoms
Small kidneys in between attacks
it takes weeks of treatment after symptoms
disappear
ALPORT SYNDROME
• IgA Nephropathy
• A form of hereditary nephritis
synpharyngitic
• a genetically heterogeneous disease caused by
during the infection, there is onset of hematuria, mutations in the genes coding for type IV collagen
edema and hypertension • X-linked disease caused by mutation in the COL4A5
after 2-3 days of treatment, hematuria and other gene encoding for the alpha chain of type IV collagen
symptoms disappears
CLINICAL MANIFESTATIONS
WAYS TO QUANTIFY THE AMOUNT OF • Asymptomatic microscopic hematuria which maybe
PROTENURIA
intermittent in girls and younger boys
• 24 hr urine collection – cumbersome, prone to
Always ask if there is kidney disease in the family;
collection error
With episodes of fever or recurrence of hematuria,
• Albumin/creatinine ratio is a simple and accurate
always check for renal indices
method of quantifying proteinuria
• Single or Recurrent episodes of gross hematuria
Ex. A/C ratio of 0.2 mg protein/mg creatinine
• occur 1-2 days after a URTI (50% of patients)
equivalent to urine protein of < 0.2g/24 h
• Proteinuria frequently seen in males.
• Urine electrophoresis – to determine the type of
• Progressive proteinuria common by the 2nd decade of
protein present
life, severe enough to cause nephrotic syndrome
• Extrarenal manifestations include hearing deficits and
Table 1. Nephrotic vs Nephritic Syndromes. Source: Doc’s
ocular abnormalities.
Lecture
• Bilateral sensorineural hearing loss which is never
Feature Nephrotic Nephritic
congenital in onset occur in hemizygous males with X-
Onset Insidious Abrupt
Edema ++++ ++
linked AS
BP Normal Raised • Higher risk for progressive renal disease
JVP Normal/Low Raised
Proteinuria ++++ ++
PROGNOSIS AND TREATMENT
• Risk factors for progression are gross hematuria during
Hematuria May/may not +++
childhood, nephrotic syndrome, and prominent GBM
occur
thickening.
RBC Casts Absent Present
• The risk of progressive renal dysfunction leading to end
Albumin Low Normal/Slightly
Decreased stage renal disease (ESRD) is highest among
hemizygotes and autosomal recessive homozygotes.
Table 2. Clinical Manifestation of Glomerular Diseases. ESRD occurs before age 30 yr in approximately 75%
Source: Doc’s Lecture of hemizygotes with X-linked AS. The risk of ESRD in
Nephritic Nephrotic RPGN X-linked heterozygotes is 12% by age 40 yr and 30%
Syndrome Syndrome by age 60 yr.
Oliguria Proteinuria >3g/dL ARF over • No specific therapy is available to treat AS. Although
Hematuria High cholesterol days or • Angiotensin-converting enzyme inhibitors can slow the
RBC Casts levels weeks rate of progression. Careful management of renal
Proteinuria usually Low serum albumin Proteinuria failure complications such as hypertension, anemia,
<3g/dL Lipiduria RBC cast and electrolyte imbalance is critical.
Edema Edema Variable • Patients with ESRD are treated with dialysis and kidney
HPN Normal BP BP Transplantation. Approximately 5% of kidney
Abrupt onset Vasculitic transplant recipients develop anti-GBM nephritis,
Usually self-limiting features

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Block XIX: Glomerulonephritides in Children 8 of 12
MD 3
 which occurs primarily in males with X-linked AS who
develop ESRD before age 30 yrs.
THIN GLOMERULAR
BASEMENT MEMBRANE DISEASE
• Presence of persistent microscopic hematuria and
isolated thinning of the basement membrane on
electron microscopy
More of a histologic diagnosis
• Sporadic/Autosomal dominant
• Microscopic hematuria is usually persistent
• There is no treatment.
Although they say that this is a benign condition,
you still see a progression from nephritic to
nephrotic. And if the child presents with nephrotic
syndrome you still manage with steroid therapy
• Progressive renal insufficiency, hypertension,
proteinuria, and extrarenal manifestations.
MEMBRANOUS NEPHROPATHY
• Most common cause of nephrotic syndrome in adults,
but an uncommon cause of hematuria in children
Malaria- the most common cause of MN worldwide
If onset of hematuria is during adolescent, 18 year
old, you may consider membranous nephropathy
• May manifest as nephritic syndrome in adolescents
suspect in cases of post-strep GN who tends to
have persistent hematuria or proteinuria beyond
the 3month period
• Histopath will determine cause.
HENOCH SCHONLEIN PURPURA
Most common small vessel vasculitis in childhood
characterized by a purpuric rash and commonly
accompanied by arthritis and abdominal pain
Approximately 50% of patients with HSP develop
Renal manifestations, which vary from asymptomatic
microscopic hematuria to severe, progressive
glomerulonephritis.
• Common in children presenting with abdominal pain,
joint pain and purpuric rash
• Hematuria or nephritis may or may not be present
• May manifest as isolated hematuria, acute nephritic
syndrome or nephrotic syndrome
EULAR / PRES CRITERIA – 2006
Mandatory Criterion:
• Palpable purpura
• Plus at least one of the following criteria:
Diffuse abdominal pain
IgA deposition in any biopsy
Arthritis/Arthalgia
Renal involvement (Hematuria / Proteinuria)
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Block XIX: Glomerulonephritides in Children
MD 3
AMERICAN COLLEGE OF RHEUMATOLOGY
CRITERIA – 1990
• Three or more of the following criteria are needed:
Age 20 years or less at disease onset
Palpable purpura
Acute abdominal pain with GI bleeding
Biopsy showing granulocytes in the walls of small
arterioles or venules in superficial layers of the
skin
PATHOGENESIS AND PATHOLOGY
• The pathogenesis of HSP nephritis appears to be
mediated by the deposition of polymeric
immunoglobulin A (IgA) in glomeruli. This is analogous
to the same type of IgA deposits seen in systemic
small vessels, primarily those of the skin and intestine.
• The glomerular findings can be indistinguishable from
those of IgA nephropathy. IgA deposits are present by
immunofluorescence, and a broad spectrum of
glomerular lesions that can range from mild
proliferation to necrotic and crescentic changes can be
seen.
PROGNOSIS AND TREATMENT
• The prognosis of HSP nephritis for most patients is
excellent. Spontaneous and complete resolution of the
nephritis typically occurs in those with mild initial
manifestations (isolated hematuria with insignificant
proteinuria). However, such patients can progress to
severe renal involvement, including development of
chronic renal failure.
• Patients with acute nephritic or nephritic syndrome at
presentation have a guarded renal prognosis,
especially if they are found to have concomitant
necrosis or substantial crescentic changes on renal
biopsy.
• Untreated, the risk of developing chronic kidney
disease, including renal failure, is2-5% in all patients
with HSP but almost 50% in those with the most
severe clinical and histologic features.
• No studies have demonstrated whether short courses
of oral corticosteroids administered promptly after
onset of HSP have a significant favorable effect on the
subsequent development or severity of subsequent
HSP nephritis. Several uncontrolled studies have
reported benefit from aggressive immunosuppression
(high-dose and extended courses of corticosteroids
with cyclophosphamide or azathioprine) in patients
with poor prognostic features who might be expected
to have a high risk of chronic renal failure.
• Tonsillectomy has been proposed as an intervention for
HSP nephritis, but it does not appear to have any
measurable effect.
• Mild HSP nephritis does not require treatment because
it usually resolves spontaneously.
9 of 12
• Aggressive therapy with careful monitoring may be Clinical Presentation:
reasonable in those with the most severe HSP • Possible recent exposure to E.Coli, most cases are
nephritis (>50% crescents on biopsy). sporadic
• Prodromal diarrhea followed by acute renal failure
HEMOLYTIC UREMIC SYNDROME • Average interval between E. coli exposure and illness
One of the most common causes of community is 3 days (1 – 8 days)
acquire acute kidney failure in young children. • Hemorrhagic diarrhea (70 %) within 1 to 2 days
• More common in children less than 1 year old • Vomiting 30 – 60 %
manifesting with acute gastroenteritis • Fever 30 %
• Develop oliguria or anuria after several episodes of • Leukocytosis
vomiting and loose bowel movement • HUS is usually diagnosed 6 days after onset of
• Must complete the TRIAD of acute renal failure, diarrhea
anemia and previous history of acute gastroenteritis • STX E. coli is shed in the stools several weeks after
suspect HUS in a pale infant who had episodes of symptoms resolve
vomiting or diarrhea with an elevated creatinine
and BUN, and no urine output for the past 24 NON SHIGA – TOXIN ASSOCIATED HUS
hours • Atypical or non-diarrhea associated HUS
• Must be considered in infant presenting with hematuria • 10 % of cases in children
and acute renal failure • Sporadic / familial
Rule out HUS first because HUS it warrants more • Poor outcome ( > 50% ESRD)
immediate treatment, they tend to progress fast to
renal failure.
Typical disease follows a diarrheal prodrome
enteropathogenic E. coli or other bacterial that
produce Shiga – like toxin (STX). STX translocates
into the circulation binding to neutrophils, platelets
and erythrocytes and is carried to the small
capillaries
Pathologic hallmark: deposition of fibrin – platelet
thrombi in affected organs
common cause of ARF in patients younger than 5
years old, requiring acute dialysis; 10 – 20 % of
children develop ESRD

HISTOLOGY
• Renal biopsy is not necessary for the diagnosis
• Histologic lesions: Glomerular microangiopathy
(swollen glomerular epithelial cells); arteriolar
PROGNOSIS AND TREATMENT
thrombotic microangiopathy; acute cortical necrosis • The primary approach that has substantially improved
acute outcome in HUS is early recognition of the
ETIOLOGY disease, monitoring for potential complications, and
SHIGA – TOXIN ASSOCIATED HUS
meticulous supportive care. Supportive care includes
• Typical or Diarrhea associated HUS
careful management of fluid and electrolytes including
• Most common form in children
correction of volume deficit, control of hypertension,
• Prodromal episode of bloody diarrhea o Diagnosis of
and early institution of dialysis if the patient becomes
EHEC infection: Stool culture ( Higher rate of stool
anuric or significantly oliguric.
isolation in the first 6 days after onset of diarrhea)
• The acute prognosis, with careful supportive care, for
• 10 – 15 % of children with E. coli O157 colitis
diarrhea associated HUS has <5% mortality in most
eventually develop HUS
major medical centers. Red cell transfusions are
• STX producing Shigella dysenteriae (Asia and Africa):
usually required because hemolysis can be brisk and
more severe.
recurrent until the active phase of the disease has
• Acute mortality rate of 15%
resolved.
• > 40% leads to CRF
• Half of the patients require dialysis support during the
• Good prognosis
acute phase of the disease. Most recover renal
function completely, but of surviving patients, 5%

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Block XIX: Glomerulonephritides in Children 10 of 12
MD 3
 remain dependent on dialysis, and up to 20-30% are 3. Which cause of acute nephritic syndrome may
left with some level of chronic renal insufficiency. recur even after kidney transplantation?
• The prognosis for HUS not associated with diarrhea is a. FSGS
more severe. Pneumococci-associated HUS causes b. PSGN
increased patient morbidity, with mortality reported as c. Alport syndrome
20%. d. HUS
• The familial, genetic forms of HUS can be insidiously 4. Primary treatment for IgA Nephropathy
progressive or relapsing diseases and have a poor a. Blood glucose control
prognosis. Identification of specific factor deficiencies b. Anti-IgA antibody
in some of these genetic forms provides opportunity c. Antibiotics
for specific replacement therapy to improve outcomes. d. None of the above
5. Best diagnostic to quantify proteinuria
REVIEW QUESTIONS a. 24 hour urine specimen
1. Which isn’t a clinical criterion for nephritic b. Urine dipstick method
syndrome? c. A/C ratio
a. Hematuria d. Urine electrophoresis
b. Anuria
c. Edema Answers: B, C, A, D, C
d. Hypertension
2. Which isn’t a clinical criterion for nephrotic REFERENCES
syndrome? • Dr. Alcala’s Lecture
a. Hypercholesterolemia • Nelson’s Pediatrics
b. Edema • Upclass’ Notes
c. Hypoalbuminemia
d. Normotension
APPENDIX

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Block XIX: Glomerulonephritides in Children 11 of 12
MD 3
CCetC
Block XIX: Glomerulonephritides in Children 12 of 12
MD 3