Pediatric Nephrotic

syndrome/Acute
Glomerulonephritis
Dr Arif
Nephrotic Syndrome in
children
Objectives

• Identify the etiology of nephrotic syndrome.

• Review the presentation of patients with nephrotic
syndrome.
• Summarize the treatment and management options
available for nephrotic syndrome.
• Describe interprofessional team strategies for
improving care and outcomes in patients with
nephrotic syndrome.
What is Nephrotic syndrome

 Nephrotic syndrome is a disorder of the

kidneys that results from increased
permeability of the glomerular filtration
barrier. It is characterized by 4 major clinical
characteristics that are used in establishing
the diagnosis: proteinuria, hypoalbuminemia,
edema, and hyperlipidemia.
What is Nephrotic range proteinuria

 Nephrotic-range proteinuria in a 24-hour urine

collection is defined in adults as 3.5 g of
protein or more per 24 hours.
 In children it is defined as protein excretion of
more than 40 mg/m2/hr to account for varying
body sizes throughout childhood.
 In both adults and children, a first-morning
urine protein/creatinine ratio of 2-3 mg/mg or
more indicates nephrotic-range proteinuria.
Epidemiology

 United States: 2-7 cases per 100,000 children younger than 16

years.
 The cumulative prevalence rate is approximately 16 cases per
100,000 individuals.
 New Zealand : 20 cases per million children under age 15 years.
 In specific populations, such as those of Finnish or Mennonite
origin, congenital nephrotic syndrome may occur in 1 in 10,000 or
1 in 500 births, respectively.
 In preadolescents, minimal-change nephrotic syndrome (MCNS)
makes up 85-95% of all cases of nephrotic syndrome
 In adolescents and young adults, the prevalence is 50%, while in
adults, MCNS accounts for 10-15% of primary nephrotic syndrome
cases. 
Race-, sex-, and age-related
demographics
• In children, MCD is found twice as frequently in boys than in girls;
in adults, however, the frequency is the same between the sexes

• The incidence of MCD peaks in children aged 2 years, with

approximately 80% being younger than 6 years at the time of
diagnosis

 Black and Hispanic children appear to have an increased risk of

steroid-resistant nephrotic syndrome and FSGS

 Inchildren younger than 8 years at onset, the ratio of males to

females varies from 2:1 to 3:2 in various studies
 Of patients with MCNS, 70% are younger than 5 years
Pathophysiology

It is postulated that MCD is a disorder of T cells,

which release a cytokine that injures the
glomerular epithelial foot processes. This, in
turn, leads to a decreased synthesis of
polyanions. The polyanions constitute the normal
charge barrier to the filtration of
macromolecules, such as albumin. When the
polyanions are damaged, leakage of albumin
follows. 
 Some of the cytokines that have been studied
in MCD are interleukin-12 (IL-12) and
interleukin-4 (IL-4). IL-12 levels have been
found to be elevated in peripheral blood
monocytes during the active phase and
normalized during remission
Etiology

 Causes of INS include the following:

 Minimal change nephrotic syndrome (MNCS)
 Focal segmental glomerulosclerosis (FSGS)
 Membranoproliferative glomerulonephritis
(MPGN)
 Membranous glomerulonephritis (MNG)
 C3 glomerulonephritis
 IgA nephropathy
 Idiopathic crescentic glomerulonephritis
genetic or congenital 
 Causes of genetic or congenital nephrotic syndrome include the
following:
• Finnish-type congenital nephrotic syndrome (NPHS1, nephrin)
• Denys-Drash syndrome (WT1)
• Frasier syndrome (WT1)
• Diffuse mesangial sclerosis (WT1, PLCE1)
• Autosomal recessive, familial FSGS (NPHS2, podocin)
• Autosomal dominant, familial FSGS (ACTN4, α-actinin-4, TRPC6)
• Nail-patella syndrome (LMX1B)
• Pierson syndrome (LAMB2)
• Schimke immuno-osseous dysplasia (SMARCAL1)
• Galloway-Mowat syndrome
• Oculocerebrorenal (Lowe) syndrome
Infections

 Infections that can cause secondary nephrotic

syndrome include the following:
• Congenital syphilis, toxoplasmosis, CMV,
rubella.
• Hepatitis B and C
• HIV infection/acquired immunodeficiency
syndrome (AIDS)
• Malaria
Drugs

 Drugs that can cause secondary nephrotic

syndrome include the following:
• Penicillamine
• Gold
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Interferon
• Mercury
• Heroin
• Pamidronate
• lithium
Systemic disorders
 Systemic diseases that can cause secondary nephrotic
syndrome include the following:
• Systemic lupus erythematosus
• Malignancy: Lymphoma, leukemia
• Vasculitis: Wegener granulomatosis (granulomatosis with
polyangiitis), Churg-Strauss syndrome (eosinophilic
granulomatosis with polyangiitis), polyarteritis nodosa,
microscopic polyangiitis, Henoch-Schönlein purpura
 (HSP)
• Immune-complex–mediated: Poststreptococcal
(postinfectious) glomerulonephritis
History

 Edema is the presenting symptom in about 95% of

children with nephrotic syndrome
 A history of a respiratory tract infection immediately
preceding the onset of nephrotic syndrome is frequent
 A child might be brought to medical attention for
symptoms of infection, such as fever, lethargy,
irritability, or abdominal pain due to sepsis or peritonitis
 Except in rare cases of familial INS, no significant
family history of kidney disease or INS is usually noted.
Physical Examination

 The most common clinical finding is edema.

 In those children with marked ascites, mechanical restriction
to breathing may be present, and the child may manifest
compensatory tachypnea.
 Hypertension
 Abdominal tenderness might indicate peritonitis
 Hypotension and signs of shock can be present in children
with sepsis.
 Thrombosis can cause various findings, including tachypnea
and respiratory distress (pulmonary thrombosis/embolism),
hematuria (renal vein thrombosis), and seizure (cerebral
thrombosis).
Approach Considerations

Initial laboratory testing should include

the following
• Urinalysis
• Urine protein quantification (by first-morning
urine protein/creatinine ratio or 24-hour urine
protein measurement)
• Serum albumin
• Lipid panel
Once the presence of nephrotic syndrome has
been established, the next task is to determine
whether the nephrotic syndrome is primary
(idiopathic) or secondary to a systemic disorder 
• Complete blood cell (CBC) count
• Metabolic panel (serum electrolytes, blood urea nitrogen [BUN] and
creatinine, calcium, phosphorus, and ionized calcium levels)
• Testing for human immunodeficiency virus (HIV), hepatitis B and C
viruses
• Complement studies (C3, C4)
• Antinuclear antibody (ANA), anti–double-stranded DNA antibody, anti-
neutrophil cytoplasmic antibodies (in selected patients)
Other tests and procedures in selected
patients may include the following
• Genetic studies
• Kidney ultrasonography
• Chest radiography
• Mantoux test
• Kidney biopsy (age < 1 year or >12 years, or other
circumstances)
Kidney Biopsy

 A kidney biopsy is not indicated for the first

presentation of INS in children aged 1-12 years
unless the history, physical findings, or laboratory
results indicate the possibility of secondary
nephrotic syndrome.
  Kidney biopsy is indicated in patients younger than
1 year, when genetic forms of congenital nephrotic
syndrome are more common, and in patients older
than 12 years, when chronic glomerular diseases
such as FSGS have a higher incidence.
A kidney biopsy is also indicated if the
patient has any of the following:
• Symptoms of systemic disease (eg, fever, rash, joint pain)
• Laboratory findings indicative of secondary nephrotic
syndrome (eg, positive ANA result, positive anti–double-
stranded DNA antibody findings, low complement
levels)
• Elevated creatinine levels unresponsive to correction of
intravascular volume depletion
• A relevant family history of kidney disease
Treatment & Management

 A trial of corticosteroids is the first step in the treatment of idiopathic

nephrotic syndrome (INS) in which kidney biopsy is not initially
indicated. Thus, patients may be considered for steroid treatment prior to
kidney biopsy if they meet all of the following criteria:
• Age 1-12 years
• Normal kidney function
• No macroscopic (gross) hematuria
• No symptoms of systemic disease (fever, rash, joint pain, weight loss)
• Normal complement levels
• Negative antinuclear antibody (ANA) assay
• Negative viral screens (ie, for human immunodeficiency virus [HIV],
hepatitis B and C viruses)
• No family history of kidney disease
Corticosteroid Therapy

• Initial treatment: Oral prednisone, starting as a

daily dose of 60 mg/m2/day or 2 mg/kg/day
(maximum, 60 mg/day) for 4-6 weeks. After
4-6 weeks, switch to 40 mg/m2 or 1.5 mg/kg
(maximum, 40 mg) on alternate days for 2-5
months with tapering, with a minimum total
duration of treatment of 12 weeks.
Diuretic Therapy

 Diuretic therapy may be beneficial,

particularly in children with symptomatic
edema. Loop diuretics, such as
furosemide (starting at 1-2 mg/kg/day), may
improve edema; their administration, however,
should be handled with care because plasma
volume contraction may already be present,
and hypovolemic shock has been observed
with overly aggressive therapy.
Antihypertensive Therapy

 Antihypertensive therapy should be given when

hypertension is present and particularly if it
persists, but caution should be exercised. In some
patients, the hypertension will respond to diuretics.
Angiotensin-converting enzyme (ACE) inhibitors
or angiotensin II receptor blockers (ARBs) may
also contribute to reducing proteinuria but should
be used cautiously in the presence of acute kidney
failure or volume depletion because they can
worsen kidney function in these settings.
Acute
Glomeruonephritis(AGN)
Objectives

• Review the etiology of glomerulonephritis.

• Summarize the physical findings associated with
glomerulonephritis.
• Outline the management considerations for the
different diseases grouped under the term
'glomerulonephritis.'
• Describe inter-professional team strategies for
improving care coordination and communication
to improve outcomes for patients affected by
glomerulonephritis.
 Theterm "glomerulonephritis" encompasses a
subset of renal diseases characterized by
immune-mediated damage to the basement
membrane, the mesangium, or the capillary
endothelium, resulting in hematuria,
proteinuria, and azotemia.
Types Glomerulonephritis
 Acute forms of glomerulonephritis (GN) can result from
either a primary renal cause or a secondary illness that
causes renal manifestations. For instance, acute post-
streptococcal glomerulonephritis (PSGN) is a typical
example of acute glomerulonephritis secondary to a
streptococcal infection
 Most forms of glomerulonephritis are considered
progressive disorders. Without timely therapy, progress
to chronic glomerulonephritis (characterized by
progressive glomerular damage and tubulointerstitial
fibrosis leading to a reduced glomerular filtration rate)
Etiology

 Etiologicalclassification of
glomerulonephritis can be made based on
clinical presentation, ranging from severe
proteinuria (>3.5 g/day) and edema qualifying
for the nephrotic syndrome to a nephritic
syndrome where hematuria and hypertension
are more prominent while proteinuria is less
pronounced
Nephrotic Glomerulonephritis

• Minimal change disease

• Focal segmental glomerulosclerosis
• Membranoproliferative glomerulonephritis
• Membranous nephropathy
• HIV associated nephropathy
• Diabetic nephropathy
• Amyloidosis
Nephritic Glomerulonephritis
• IgA nephropathy
• Henoch Schonlein purpura (HSP)[7]
• Post streptococcal glomerulonephritis.
• Anti-glomerular basement membrane disease
• Rapidly progressive glomerulonephritis
• Granulomatosis with polyangiitis
• Eosinophilic granulomatosis with polyangiitis
• Polyarteritis nodosa
• Idiopathic crescentic glomerulonephritis
• Goodpasture syndrome
• Lupus nephritis
• Hepatitis C infection
Modern classification of
glomerulonephritis
1. Immune-complex GN - IgA nephropathy, IgA vasculitis,
infection-related GN, lupus nephritis, and fibrillary GN with
polyclonal Ig deposits
2. Pauci-immune GN - PR3-ANCA GN, MPO-ANCA GN, and
ANCA-negative GN
3. Anti-glomerular basement membrane (GBM) GN - Anti-GBM
GN
4. Monoclonal Ig GN - Proliferative GN with monoclonal Ig
deposits, monoclonal Ig deposition disease, fibrillary GN with
monoclonal Ig deposits, and immunotactoid glomerulopathy
5. C3 glomerulopathy - C3 glomerulonephritis, dense deposit
disease
Epidemiology

 Glomerulonephritis (GN) is a prominent cause of

renal impairment. It leads to 10% to 15% of end-
stage renal disease cases in the United States.
 Glomerulonephritis constitutes 25% to 30% of all
end-stage renal disease cases
 IgA nephropathy has been found to be the most
common cause of glomerulonephritis worldwide
 Incidence of post-streptococcal glomerulonephritis
has declined in most developed countries
Pathophysiology

 The underlying pathogenetic mechanism common to all

of these different varieties of glomerulonephritis (GN) is
immune-mediated, in which both humoral as well as cell-
mediated pathways are active leading to

• Proteinuria
• Hematuria
• Reduction in creatinine clearance, oliguria, or anuria
• Active urine sediments, such as RBCs and RBC casts
 This leads to intravascular volume expansion, edema,
and systemic hypertension.
History and Physical

Some symptoms occur primarily and include:

• Hypertension
• Edema (peripheral or periorbital) - initially in the dependent
areas/areas with low tissue tension
• Abnormal urinary sedimentation
• Hematuria – microscopic or gross
• Oliguria
• Azotemia
• Shortness of breath or dyspnea on exertion
• Headache - secondary to hypertension
• Confusion - secondary to malignant hypertension
• Possible flank pain
Symptoms specifically related to an underlying
systemic disease:
• Triad of sinusitis, pulmonary infiltrates, and nephritis –
granulomatosis with polyangiitis
• Nausea, vomiting, abdominal pain, purpura -  Henoch-
Schönlein purpura
• Arthralgias - systemic lupus erythematosus (SLE)
• Hemoptysis - Goodpasture syndrome or idiopathic
progressive glomerulonephritis
• Skin rashes – in hypersensitivity vasculitis, SLE,
cryoglobulinemia, Henoch-Schönlein purpura
The following signs of excess fluid in the
body:
• Periorbital and/or peripheral edema
• High blood pressure
• Fine inspiratory crackles due to pulmonary
edema
• Raised jugular venous pressure
• Ascites and pleural effusion
Other signs to look for include the
following:
• Vasculitic rash (as with Henoch-Schönlein
purpura, or lupus nephritis)
• Pallor
• Renal angle fullness or tenderness
• Abnormal neurologic examination or
altered sensorium
• Arthritis
Investigations

Blood
• Complete blood count - A decreased hematocrit may suggest a dilutional type of
anemia. In the background of an infectious cause, pleocytosis may be apparent.
• Serum electrolytes - Potassium levels may be raised in patients with severe renal
impairment.
• Renal function tests - BUN and creatinine levels are raised, demonstrating a degree
of renal impairment. In addition, the glomerular filtration rate (GFR) may be low.
• Liver function tests - May point towards the underlying etiology.
• Immunoglobulins
• C-reactive protein (CRP)
• Complement (C3, C4 levels)
 Autoantibodies, such as antinuclear antibodies (ANA), anti-neutrophil cytoplasmic
antibodies (ANCA), and anti-ds-DNA, 
 Antistreptolysin O titer (ASOT)
 Hepatitis serology - As infectious hepatitis can lead to glomerulonephritis of
various types
Urine
 The urine is usually dark, and the specific gravity is
more than 1.020 with RBCs and RBC casts. The 24-hour
urinary protein excretion and creatinine clearance may
help establish the degree of renal impairment and
proteinuria. The following parameters are usually
helpful:
• Microscopy, culture, and sensitivity
• Bence Jones protein
• Albumin to creatinine or protein to creatinine ratio
• RBC casts
Renal Biopsy
 The examination of glomerular lesions via a renal biopsy provides the
diagnosis of glomerulonephritis by answering the following queries:
• Approximate proportion of involved glomeruli (focal vs. diffuse)
• Approximate involvement of each glomerulus (segmental vs. global)
• Presence of hypercellularity
• Any evident sclerosis
• Any deposits on immunohistology (immunoglobulins, light chains,
complement)
• Electron microscopy findings - precise localization of deposits. Exact
ultrastructural appearance. Podocyte appearance
• Presence of tubulointerstitial inflammation, atrophy, or fibrosis
• Evident vessel-related pathology
Treatment / Management

A) Specific management revolves around

immunosuppression, which in turn is governed by
factors like:
• Histological diagnosis
• Disease severity
• Disease progression
• Comorbidities 
  The available options include: 
• High-dose corticosteroids
• Rituximab (a monoclonal antibody that causes the lysis of B-lymphocytes)
• Cytotoxic agents (e.g., cyclophosphamide, along with glucocorticoids are of
value in severe cases of post-streptococcal glomerulonephritis)
• Plasma exchange (glomerular proliferative nephritis, pauci-immune
glomerulonephritis – used temporarily till chemotherapy takes effect)
 B) With progression into chronicity, general management is done on the lines of
chronic kidney disease:
1. Keeping track of the renal function tests (RFTs), serum albumin, and urine protein
excretion rate.
2. By controlling the BP and inhibiting the renin-angiotensin axis through Loop
diuretics, which serve two purposes; the removal of excess fluid and the correction
of hypertension. Angiotensin-converting enzyme inhibitors (ACEIs) are frequently
the first choice for managing hypertension and chronic kidney disease (CKD).
Angiotensin 2 receptor blockers (ARBs) have been found to halt CKD progression
in diabetic or nondiabetic renal disease cases, much like ACEIs.
3. For individuals with severe/refractory hypertension with/without encephalopathy,
vasodilators (e.g., nitroprusside and nifedipine) can be used.
4. Clinicians can manage the complications associated with progressive chronic
disease, including anemia, bone mineral disorders, acidosis, cardiovascular
disease, and restless legs/cramps.
5. Appropriate counseling regarding diet.
6. Preparation for renal replacement therapy (RRT), if needed.
Prognosis

 PSGN has an excellent prognosis, especially in children with

complete recovery, usually occurring within 6 to 8 weeks. In
adults, around 50% of the patients continue to have reduced
renal function, hypertension, or persistent proteinuria.
 Henoch-Schönlein purpura is typically a self-limited illness
that demonstrates an excellent prognosis in patients without
renal involvement,
 Approximately 1% of patients with Henoch-Schönlein purpura
will develop ESRD and require renal transplantation
 Membranoproliferative glomerulonephritis progresses to
ESRD inevitably, despite therapy. Also, the frequency of
recurrence is high even after a kidney transplant