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 and a urine specific gravity of 1.015. What is your
II. Acute Nephritic Syndrome primary impression of Mark’s case?
A. Acute Post-Streptococcal Glomerulonephritis
III. Acute Nephrotic Syndrome
Ans: Acute Nephrotic Syndrome
B. Idiopathic Nephrotic Syndrome Hemolytic uremic syndrome (HUS) commonly affects
IV. Supplementary Notes young children and typically presents with
Review Questions gastroenteritis as a prodrome
References
Appendix
INTENDED LEARNING OBJECTIVES
LECTURER BOOK REFERENCE OLD TRANS 1. Recognize the clinical presentation of a child
presenting with acute nephritic syndrome
2. Differentiate acute nephritic syndrome from acute
CASE nephrotic syndrome
Case No. 1 3. Discuss acute post-streptococcal glomerulonephritis
ANA, a 10-year-old female child was brought to the OPD as the pathognomonic acute nephritic syndrome in
for consult. children
2 weeks PTC, she had symptoms of URTI, associated 4. Discuss idiopathic nephrotic syndrome as the
with throat pain, fever, and nasal congestion pathognomonic acute nephrotic syndrome in
1 day PTC, puffy eyelids were noted upon waking up in children
the morning, with associated headache and vomiting of 5. Recognize other common nephritides in the pediatric
previously taken in breakfast. age group
Prior to leaving home, she had one episode of grossly
red urine. What is your primary impression? I. ACUTE NEPHRITIC SYNDROME
Ans: Acute Post-Streptococcal Glomerulonephritis CLINICAL CRITERIA
The edema of nephritic syndrome is typically most 1. Edema
prominent early in the morning The edema of nephritic syndrome can be severe
enough to cause dyspnea, shortness of breath or
Case No. 2 even respiratory compromise
An 18-year-old female, single, adolescent with OB score The edema of nephritic syndrome is most
of G1P0, & 23 weeks pregnant was referred by the prominent in the morning, and on the patient’s
OB-GYNE service due to persistent abdominal pain dependent side, but gradually recedes as the day
and hematuria progresses
PE revealed alopecia, fine maculopapular rashes in the 2. Hypertension
auricular area, & swelling of the left ankle joint. The hypertension of nephritic syndrome may be
CBC revealed anemia with mild thrombocytopenia. severe enough to cause hypertensive
Urinalysis revealed a urine specific gravity of 1.015, encephalopathy, seizures, and even status
hazy reddish urine with packed filled RBC, pus cells of epilepticus
3-5/hpf, negative sugar, & (++) proteins. What is your The hypertension of nephritic syndrome is
strongest consideration? primarily due to fluid retention. This is in contrast
Ans: Lupus Nephritis with nephrotic syndrome where the intravascular
Pregnancy is an exacerbating factor for lupus volume is depleted due to the third-spacing brought
about by hypoalbuminemia
Case No. 3 3. Hematuria
Mark, an 8-year-old male was brought to the ER for The most common reason for consult, but is also
facial puffiness of 1-week duration, which progressed the most benign among the clinical criteria. It may be
to abdominal distention & anasarca microscopic or gross
PE revealed a HR of 80bpm, RR of 20 cpm, BP of 90/60 4. Oliguria
mmHg. 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

CCetC Group No. 39 1 of 12

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
Figure 1. Common Biopsy Findings in Children. Source: Journal of the
• IgA nephropathy Korean Society of Pediatric Nephrology (2017)
• Alport syndrome (hereditary nephritis)
• Thin glomerular basement membrane nephropathy 1. Recurrent macroscopic hematuria (35.8%)
• Post-infectious GN (post-strep) 2. Nephrotic syndrome associated with hematuria or
HTN (10.7%)
• Membranous nephropathy
3. Persistent microscopic hematuria with proteinuria
• Membranoproliferative GN (10.1%)
• Focal segmental glomerulosclerosis (FSGS) 4. Steroid-resistant, steroid-dependent, or frequent-
• Antiglomerular basement membrane disease relapsed nephrotic syndrome (10.1%)
5. Evaluation of renal involvement in systemic disease
IgA nephropathy is the leading cause of (8.5%)
glomerulonephritis secondary to an isolated renal 6. Persistent microscopic hematuria (7.2%)
7. Others (17.6%)
disease However, post-infectious (or post-strep)
glomerulonephritis is the most common cause in our
locality ACUTE POST-STREPTOCOCCAL
Membranous nephropathy is typically a disease of GLOMERULONEPHRITIS (APSGN)
adults • A classic example of acute nephritic syndrome
Membranoproliferative GN is an autoimmune disease • Characterized by a sudden onset of gross hematuria,
that typically follows an infection and so may be edema, hypertension, and renal insufficiency
misdiagnosed as post-strep GN; it should be • The most common cause of GN in our locality, but is
suspected when the manifestations of the patient surpassed by IgA nephropathy worldwide
does not follow the typical course of a post-strep GN • Also the most common glomerular cause of gross
and can be confirmed via biopsy hematuria in children
FSGS is the worst diagnosis among the following and • Follows infection of the throat or skin by certain
may also cause nephrotic syndrome nephritogenic strains of Group A β-hemolytic
streptococci
2. Multisystem Diseases Trends show that in the Philippines, IgA nephropathy
• Systemic lupus erythematosus with nephritis cases are closing in as the most common cause of
• Henoch-Schonlein purpura with nephritis nephritic syndrome because cases of sore throat are
• Wegener granulomatosis now detected earlier and treated with antibiotics
• Polyarteritis nodosa (PAN) earlier, preventing their progression to PSGN
• Goodpasture syndrome Dr. Alcala urged us to read on the characteristics of
• Hemolytic uremic syndrome (HUS) Group A β-hemolytic streptococci
• Sickle cell glomerulopathy
• HIV nephropathy PATHOLOGY
• Kidneys appear symmetrically enlarged & affected
The typical picture of HUS is hematuria and because of the autoimmune mechanism of PSGN
abdominal pain, with GI symptoms as a prodrome. It • All glomeruli appear enlarged & relatively bloodless
may be differentiated from SLE through the type of with mesangial cell proliferation & an increase in
rash presented and the presence of elevated BUN & mesangial matrix
creatinine levels • PMN leukocytes are commonly seen in the glomeruli
Sickle cell glomerulopathy is seldom seen in the during the early stages of the disease
Philippines • Crescents and interstitial inflammation may be seen in
HIV nephropathy is a new entity & cases are currently severe and rapidly progressive cases
rising • 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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 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
Figure 2. The Glomerulus as seen in PSGN
Phase 1: Oliguric
PATHOGENESIS • Edema, hypertension, & oliguria
The Immune Complex Theory Edema is due to salt & water retention
• Glomerular deposition of nephritogenic streptococcal • Non-specific symptoms such as lethargy, abdominal
antigens & subsequent formation of immune or flank pain, & fever are also common
complexes in situ and/or the deposition of circulating • Nephrotic syndrome may also develop in 10-20% of
antigen-antibody complexes (Oda et al., 2010) cases
• Antigens considered potential causes of APSGN • This acute phase generally resolves within 6-8 weeks
Nephritis-associated plasmin receptor (NAPlr)- A low-salt diet and fluid volume restriction (based on
streptococcal glyceraldehyde-3-phosphate body surface area & daily output) can be given as
dehydrogenase adjunct management
Cationic cysteine proteinase-streptococcal Hypertension should be suspected if the patient
pyogenic exotoxin B (SPEB) presents with vomiting, dizziness, or headache
A Foley catheter may be inserted to properly assess
Educate children with APSGN regarding what renal output. An adequate urine output is at least 1
happened to their kidneys. This is the best way to cc/kg/hr
promote compliance to a low-salt diet (esp. one Other factors to investigate include the duration from
without fast food) last urine output, volume, color, and character of the
Dr. Alcala also gives McDonald’s to patients with urine
APSGN after 6-12 weeks of management as a price Phase 2: Diuretic
and to identify patients that were misdiagnosed as • Edema resolves, & diuresis ensues
APSGN. If manifestations are triggered after 6-12 • Dehydration & electrolyte imbalances should be
weeks, then suspect a different diagnosis monitored
Closely monitor sodium levels which are closely
CLINICAL MANIFESTATIONS related with hydration status and also for
• Most common in children 5-12 years old hypokalemia, especially in those taking loop diuretics
• Uncommon before the age of 3 years Phase 3: Convalescence
• Typical patients develop acute nephritic syndrome 1- Returns to normal but you have to manage the
2 weeks after a streptococcal pharyngitis or 3-6 diuretic phase since in some cases patients go back
weeks after a streptococcal pyodermata already having severe dehydration
• Symptoms vary from asymptomatic hematuria to
acute renal failure, as well as varying degrees of DIAGNOSIS
hypertension, edema, & oliguria (<1 cc/kg/hr) • Urinalysis: (+) RBC, RBC casts, proteinuria, & PMNs
Though rare, APSGN should still be suspected in • Mild normocytic anemia may be present due to
patients 3 to 18 years old hemodilution and low-grade hemolysis
Look for healed skin lesions in the extremities • C3 level is usually reduced
Cases of APSGN that are referred late should be • (+) Throat culture for streptococci
dialyzed • ASO titer (to diagnose recent infection)

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 • Anti-deoxyribonuclease (Dnase) B levels • Sodium restriction
• (+) Streptozyme test • Diuresis with IV furosemide
• Clinical diagnosis is likely in a child with acute • Calcium channel antagonists, vasodilators, or ACE
nephritic syndrome, evidence of recent strep inhibitors for hypertension
infection, & low C3 level Diuretics are the 1st line drugs for HTN, even though
• Renal biopsy is considered only if with acute renal some say CCBs are the safest in children
failure, nephrotic syndrome, absence of evidence of Use caution with ACE inhibitors and ARBs as they
strep infection, & normal complement levels OR may worsen renal hypoperfusion (esp. in the early
persistent hematuria/proteinura, diminished renal stages) and put the child at risk for further renal
function & low C3 levels for >2 months failure

C3 levels are typically decreased because they get PROGNOSIS

deposited in the glomerular basement membrane • Complete recovery in 95% of children with PSGN
(GBM), except in rapidly progressive cases where it • Mortality is avoided by appropriate management of
is elevated acute renal failure, cardiac failure, & HTN
Other causes of GN & low C3 levels include SLE, • Infrequently, the acute phase may be severe enough
and valvular lesions/shunt nephritis to cause glomerular hyalinization and CKD
ASO titers are commonly elevated after pharyngeal • Recurrences are extremely rare
infections, but rarely after streptococcal skin
infections PREVENTION
Streptozyme tests are more specific than ASO titers, • Use of early systemic antibiotics for strep throat and
but ASO is usually enough for diagnosis skin infections does not eliminate risk for PSGN
Other conditions should be considered if • Family members with acute GN should be considered
manifestations are markedly prolonged at risk and be cultured for Group A β-hemolytic
C4 is often normal or only mildly depressed streptococci, and treated, if appropriate
Confirmation of dx requires evidence of prior strep • Family pets, particularly dogs, have been reported as
infection carriers
The anti-DNase B level is the best antibody titer to
document cutaneous streptococcal infections II. ACUTE NEPHROTIC SYNDROME
MRI is indicated for patients with neurologic CLINICAL CRITERIA
symptoms and results may show reversible posterior 1. Edema
leukoencephalopathy in the parieto-occipital areas on The edema of nephrotic syndrome is typically
T2-weighted images generalized (periorbital  facial  abdominal 
Chest X-rays are indicated in those with signs of anasarca) and is secondary to protein loss and a
heart failure or respiratory distress drop in oncotic pressure
2. Normal Blood Pressure
COMPLICATIONS 3. Proteinuria
• Hypertension (60%) In children, proteinuria is defined as ≥40 mg/m2
Hypertensive encephalopathy (10%) 4. Hypercholesterolemia
─ Hypertensive encephalopathy may manifest A compensatory mechanism by the liver to
with a coma, stroke, or even cortical blindness increase oncotic pressure, & does not require
• Acute renal dysfunction treatment, unless extremely elevated (managed with
• Heart failure low doses of statins; off-label use)
• Hyperkalemia
• Hyperphosphatemia CAUSES
• Hypocalcemia A. PRIMARY (IDIOPATHIC) NEPHROTIC SYNDROME
• Acidosis (INS) – 90%
• Seizures Approximately 90% of children with nephrotic
• Uremia syndrome have INS
• It is more common in males than females (2:1) and
TREATMENT appears between the ages of 2-6 years old; but can
• Penicillin – Drug of choice appear as early as 6 months throughout adulthood.
10 day course of systemic antibiotics is • It includes multiple histologic types: minimal change
recommended to limit the spread of nephritogenic disease, mesangial proliferation, focal segmental
pathogens glomerulosclerosis, membranous nephropathy, and
membranoproliferative glomerulonephritis
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• Minimal Change Disease (MNCS) – 85% Give albumin when there is genital edema
85-90% of patients <6 years old because it’s very painful.
20-30% in adolescents When you examine the umbilicus, it would already
• Mesangial proliferation – 5% appear slit-like
• Focal segmental sclerosis (FSGS) – 10% • Misdiagnosed as an allergic disorder because of the
develops in older children • Periorbital swelling that decreases throughout the day
suspect in a child who presents with nephrotic • Anorexia, irritability, abdominal pain and diarrhea are
syndrome later than the age of 6 or those who are common.
diagnosed with nephrotic syndrome but are poorly • Hypertension and gross hematuria are uncommon
responsive to steroids or with frequently relapses They are more commonly seen in nephritic rather
Considered to be a severe form which has a than nephrotic
poorer prognosis; it is hard to achieve remission in
these cases; usually edema is intractable and DIAGNOSIS
dialysis starts from early childhood and continued • Urinalysis: 3+ or 4+ proteinuria
to adulthood. • Microscopic hematuria in 20% of children
• Spot urine: Protein/creatinine ratio exceeds 2.0
B. SECONDARY NEPHROTIC SYNDROME – 10% • Urinary protein excretion: exceeds 3.5g/24 hrs in adults
and 40mg/m2/hr in children
• Serum creatinine usually normal
IDIOPATHIC NEPHROTIC SYNDROME (INS) • Serum albumin level <2.5g/dL
Associated with primary glomerular disease without
Effect of albumin infusion is just transient. It will
evidence of a specific systemic cause temporarily evacuate fluids from the 3rd space and
cause diuresis. As soon as the albumin is excreted in
PATHOPHYSIOLOGY:
the kidney, the albumin levels will decrease again. In
• Increase in permeability of the glomerular capillary wall
nephrotic syndrome you have to give steroid therapy.
leads to massive proteinuria and hypoalbuminemia
The problem with steroid therapy is that when there is
• Cause of increased permeability is not well understood
a concomitant infection, and you give steroids, the
MINIMAL CHANGE DISEASE (MNCS) infection will be out of control leading to worsening of
• T-cell dysfunction leads to alteration of cytokines which infection.
causes loss of negatively charged glycoproteins within • Serum cholesterol and triglycerides elevated
the glomerular capillary wall • C3 and C4 are normal
Patients with MNCS are very prone to infection • Renal Biopsy NOT required in steroid responsive cases
When it clinical findings fit INS, renal biopsy is not
FOCAL SEGMENTAL GLOMERULOSCLEROSIS necessary; a good clinical history with a significant
• Plasma factor produced by lymphocytes maybe urinary parameters is already enough to have a
responsible for the increase in capillary permeability final diagnosis
This plasma factor is the reason why even if you Indications in doing renal biopsy is steroid resistant
transplant these patients with a new kidney, the nephrotics
condition still recurs in the transplanted kidney
• Mutations in podocyte proteins: Podocin & Alpha DIFFERENTIAL DIAGNOSIS
actinin 1. Protein-losing enteropathy
• 4 are associated with FSGS 2. Hepatic Failure
• Steroid resistant nephrotic syndrome is associated with 3. Congestive heart failure
mutations in NPHS2 (podocin) and WT1 genes 4. Acute/Chronic GN
You may do diagnosis by trial: start patient on 5. Protein Malnutrition
steroid tx then note if the patient responds after 4
weeks. The patient must have control of TREATMENT
proteinuria; very good responders can diurese at 7- • MCNS
10 days. Children with onset of uncomplicated nephrotic
There is also a positive expression of WT1 gene in syndrome between 1 and 8 yr of age are likely to
Wilm’s tumor have steroid-responsive MCNS, and steroid
CLINICAL MANIFESTATIONS OF INS therapy may be initiated without a diagnostic
• Children usually present with mild edema renal biopsy.
• Edema generalized with the development of ascites, Children with features that make MCNS less
pleural effusion, and genital edema. likely (gross hematuria, hypertension, renal

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Block XIX: Glomerulonephritides in Children 5 of 12
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 insufficiency, hypocomplementemia, or age <1 yr COMPLICATIONS
or >8 yr) should be considered for renal biopsy A. INFECTIONS
before treatment. • Children in relapse have increased susceptibility to
In children with presumed MCNS, prednisone bacterial infections because of urinary loss of
should be administered - 60 mg/m2/day immunoglobulins and properdin factor B
(maximum daily dose, 80 mg) in a single daily • Defective cell-mediated immunity
dose for 4-6 consecutive wk. After the initial 6-wk • Immunosupressive therapy or steroid therapy
course, the prednisone dose should be tapered • Malnutrition
to 40 mg/m2/day given every other day as a • Edema/ascites acting as a potential culture medium
single daily dose for at least 4 wk. The alternate- Even a light prick in the involved area may already
day dose is then slowly tapered and discontinued result in progressive phlebitis
over the next 1-2 months
• Steroid resistant: children who continue to have B. SPONTANEOUS BACTERIAL PERITONITIS
proteinuria (2+ or greater) after 8 wk of steroid • Most frequent type of infection
therapy; and a diagnostic renal biopsy should be • Streptococcus pneumoniae is the most common
performed. organism
Relapses should be treated with 60 mg/m2/day • E. coli also encountered
(80 mg daily max) in a single am dose until the
child enters remission (urine trace or negative for C. SEPSIS, PNEUMONIA, CELLULITIS, UTI
protein for consecutive days). The prednisone If patient presents with the classic signs and
dose is then change to alternate-day dosing as symptoms of UTI, it warrants you to request for a
noted with initial therapy, and gradually tapered urine culture.
over 4-8 wk.
Prednisone still the gold standard, 60mg/m2, can D. THROMBOEMBOLIC EVENTS
give for 6 weeks.
• Steroid dependent: relapse while on alternate day
steroid therapy or within 28 days of completing a E. CARDIOVASCULAR DISEASE
successful course of prednisone therapy. You can give FF plasma instead of albumin in cases
• Frequent relapsers - Patients who respond well to of albumin allergy
prednisone therapy but relapse ≥4times in a 12-mo
PROGNOSIS
period.
• Majority of children with steroid responsive NS have
• Steroid resistant – children who fail to respond to
frequent relapses until they grow older
prednisone therapy within 8 wk of therapy. Steroid
• SRNS unlikely to develop chronic kidney disease
resistant nephrotic syndrome is usually caused by
• FSGS poorer prognosis
FSGS (80%), MCNS, or mesangial proliferative
• Recurrent NS develop in transplant recipients with
glomerulonephritis.
FSGS
Alternative therapies for steroid-dependent
So far, there is no successful therapy for FSGS.
patients, frequent relapsers, and steroid resistant
Even if you do transplant, it also tends to recur.
patients: Cyclophosphamide (2 mg/kg) is given
as a single oral dose for a total duration of 8-12
SECONDARY NEPHROTIC SYNDROME
wk. Alternate-day prednisone therapy is often Nephrotic syndrome can occur as a secondary
continued during the course of feature of many forms of glomerular disease.
cyclophosphamide administration. Cyclosporine • Membranous nephropathy, membranoproliferative
or tacrolimus are useful as steroid-sparing glomerulonephritis, postinfectious glomerulonephritis,
agents. Mycophenolate can maintain remission in lupus nephritis, and Henoch-Schönlein purpura
children with steroid dependent or frequently nephritis can all have a nephrotic component
relapsing nephritic syndrome. • Secondary nephrotic syndrome should be suspected in
Levamisole - anthelminthic agent with patients >8 yr and those with hypertension, hematuria,
immunomodulating property renal dysfunction, extrarenal symptoms (rash,
Angiotensin-converting enzyme (ACE) inhibitors arthralgias, fever), or depressed serum complement
and angiotensin II blockers - adjunct therapy to levels.
reduce proteinuria in steroid-resistant patients. • 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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Block XIX: Glomerulonephritides in Children 6 of 12
MD 3
 nephrotic syndrome include hepatitis B virus, hepatitis • Some children display generalized mesangial
C virus, filaria, leprosy, and HIV proliferation that maybe associated crescent
formation and scarring
CAUSES OF SECONDARY INS GENERALLY
INCLUDE PATHOLOGY AND PATHOLOGIC DIAGNOSIS
A. INFECTIONS • Diagnosis REQUIRES renal biopsy, which is performed
when clinical features warrant confirmation of the
B. DRUGS diagnosis or characterization of the histologic severity,
• Also developed during therapy with numerous drugs which might affect therapeutic decisions
and chemicals. The histologic picture can resemble • Focal and segmental mesangial proliferation and
membranous glomerulopathy (penicillamine, captopril, increased mesangial matrix are seen in the glomerulus
gold, nonsteroidal anti-inflammatory drugs, mercury • Renal histology demonstrates mesangial proliferation
compounds), MCNS (probenecid, ethosuximide, that may be associated with epithelial cell crescent
methimazole, lithium), or proliferative formation and sclerosis.
glomerulonephritis (procainamide, chlorpropamide, • IgA deposits in the mesangium are often accompanied
phenytoin, trimethadione, paramethadione). by C3 complement
• The abnormalities identified in the IgA immunoglobulin
C. IMMUNOLOGIC OR ALLERGIC system have also been observed in patients with
Henoch- Schönlein purpura and lends support to the
D. MALIGNANCY hypothesis that these two diseases are part of the
• Nephrotic syndrome has been associated with same disease spectrum.
malignancy, particularly in the adult population. • Genome-wide linkage analysis suggests the linkage of
• Patients with solid tumors, such as carcinomas of the IgA nephropathy to 6q22-23 in multiplex IgA
lung and gastrointestinal tract, the renal pathology nephropathy kindreds.
often resembles membranous glomerulopathy.
• Immune complexes composed of tumor antigens and CLINICAL MANIFESTATIONS
tumor-specific antibodies presumably mediate the • Gross Hematuria may occur in association with upper
renal involvement. In patients with lymphomas, respiratory tract infection with loin pain
particularly Hodgkin lymphoma, the renal pathology IgA Nephropathy is suspected if 2-3 days prior,
most often resembles MCNS. The proposed patient had URTI and manifests with gross
mechanism of the nephrotic syndrome is that the hematuria and the patient had similar manifestation
lymphoma produces a lymphokine that increases after onset of URTI a year prior
permeability of the glomerular capillary wall. Nephrotic • Proteinuria <1000mg/24hr
syndrome can develop before or after the malignancy • Mild/moderate hypertension in children with nephritic
is detected, resolve as the tumor regresses, and return syndrome
if the tumor recurs. • Normal serum C3
An important differentiating factor; may already rule
E. METABOLIC out post-strep GN if C3 is normal
• 20-30% progress to Chronic Kidney Disease
IGA NEPHROPATHY
• Aka Berger Nephropathy
TREATMENT
They may cross between nephritic- nephrotic • Primary Treatment of IgA Nephropathy is proper
• The most common chronic glomerular disease blood pressure control
worldwide Usually, mainstay of treatment is the use of ACEIs
In our setting, it’s still Post Strep AGN or ARBs because it can also reduce proteinuria,
• Characterized by predominance of IgA within aside from lowering the BP.
mesangial deposits of the glomerulus in the absence • Fish oil, which contains anti-inflammatory omega-3
of systemic disease (symptomatic systemic lupus polyunsaturated fatty acids decrease the rate of renal
erythematosus or Henoch-Schönlein purpura) progression in adults.
• IgA is the predominant immunoglobulin deposited in • Immunosupressive therapy; alternate day
the mesangium but lesser amounts of IgG, IgM, and corticosteroids
C3. cyclosporine, mycophenylate mofetil
C3 is normal because it is not the complement that • Angiotensin-converting enzyme or Angiotensin II
deposits, it is the IgA receptor antagonists are effective in reducing
proteinuria

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Block XIX: Glomerulonephritides in Children 7 of 12
MD 3
 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
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 which occurs primarily in males with X-linked AS who AMERICAN COLLEGE OF RHEUMATOLOGY
develop ESRD before age 30 yrs. CRITERIA – 1990
• Three or more of the following criteria are needed:
THIN GLOMERULAR Age 20 years or less at disease onset
BASEMENT MEMBRANE DISEASE Palpable purpura
• Presence of persistent microscopic hematuria and Acute abdominal pain with GI bleeding
isolated thinning of the basement membrane on Biopsy showing granulocytes in the walls of small
electron microscopy arterioles or venules in superficial layers of the
More of a histologic diagnosis skin
• Sporadic/Autosomal dominant
• Microscopic hematuria is usually persistent PATHOGENESIS AND PATHOLOGY
• There is no treatment. • The pathogenesis of HSP nephritis appears to be
Although they say that this is a benign condition, mediated by the deposition of polymeric
you still see a progression from nephritic to immunoglobulin A (IgA) in glomeruli. This is analogous
nephrotic. And if the child presents with nephrotic to the same type of IgA deposits seen in systemic
syndrome you still manage with steroid therapy small vessels, primarily those of the skin and intestine.
• Progressive renal insufficiency, hypertension, • The glomerular findings can be indistinguishable from
proteinuria, and extrarenal manifestations. those of IgA nephropathy. IgA deposits are present by
immunofluorescence, and a broad spectrum of
MEMBRANOUS NEPHROPATHY glomerular lesions that can range from mild
• Most common cause of nephrotic syndrome in adults, proliferation to necrotic and crescentic changes can be
but an uncommon cause of hematuria in children seen.
Malaria- the most common cause of MN worldwide
If onset of hematuria is during adolescent, 18 year PROGNOSIS AND TREATMENT
old, you may consider membranous nephropathy • The prognosis of HSP nephritis for most patients is
• May manifest as nephritic syndrome in adolescents excellent. Spontaneous and complete resolution of the
suspect in cases of post-strep GN who tends to nephritis typically occurs in those with mild initial
have persistent hematuria or proteinuria beyond manifestations (isolated hematuria with insignificant
the 3month period proteinuria). However, such patients can progress to
• Histopath will determine cause. severe renal involvement, including development of
chronic renal failure.
HENOCH SCHONLEIN PURPURA • Patients with acute nephritic or nephritic syndrome at
Most common small vessel vasculitis in childhood presentation have a guarded renal prognosis,
characterized by a purpuric rash and commonly especially if they are found to have concomitant
accompanied by arthritis and abdominal pain necrosis or substantial crescentic changes on renal
Approximately 50% of patients with HSP develop biopsy.
Renal manifestations, which vary from asymptomatic • Untreated, the risk of developing chronic kidney
microscopic hematuria to severe, progressive disease, including renal failure, is2-5% in all patients
glomerulonephritis. with HSP but almost 50% in those with the most
• Common in children presenting with abdominal pain, severe clinical and histologic features.
joint pain and purpuric rash • No studies have demonstrated whether short courses
• Hematuria or nephritis may or may not be present of oral corticosteroids administered promptly after
• May manifest as isolated hematuria, acute nephritic onset of HSP have a significant favorable effect on the
syndrome or nephrotic syndrome subsequent development or severity of subsequent
HSP nephritis. Several uncontrolled studies have
EULAR / PRES CRITERIA – 2006 reported benefit from aggressive immunosuppression
Mandatory Criterion: (high-dose and extended courses of corticosteroids
• Palpable purpura with cyclophosphamide or azathioprine) in patients
• Plus at least one of the following criteria: with poor prognostic features who might be expected
Diffuse abdominal pain to have a high risk of chronic renal failure.
IgA deposition in any biopsy • Tonsillectomy has been proposed as an intervention for
Arthritis/Arthalgia HSP nephritis, but it does not appear to have any
Renal involvement (Hematuria / Proteinuria) measurable effect.
• Mild HSP nephritis does not require treatment because
it usually resolves spontaneously.

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Block XIX: Glomerulonephritides in Children 9 of 12
MD 3
• 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