Tutorial 4 Group D2 &

Group B2
PAGE 2

Post Streptococcal
Glomerulonephritis
 Introduction
● Group A b-hemolytic streptococcal infection of throat or skin
● Nephritogenic strains of GAS (M1, M4, M25, M49 and some strains of M12)
● Acute nephritic syndrome characterized by sudden onset of gross hematuria,
edema, hypertension and renal dysfunction
 Pathology
● Glomeruli enlarged and relatively bloodless and show a diffuse mesangial cell
proliferation, with an increase in mesangial matrix.
● Polymorphonuclear leukocyte infiltration is common in glomeruli during the early
stage of disease.
● Immunofluorescence microscopy reveals “lumpy-bumpy” deposits of
immunoglobulin and complement on the glomerular basement membrane and in
mesangium
● Electron microscope: electron-dense deposits (humps) seen on the epithelial side
of the glomerular basement membrane.
 Pathogenesis
● Morphologic studies and a low C3 level shows that it is mediated by immune
complexes.
● Molecular mimicry -> Circulating antibodies elicited streptococcal antigen react
with normal glomerular antigens, in situ immune complex formation of
streptococcal antibodies with glomerular deposited antigen and complement
activation by directly deposited streptococcal antigens
● Nephritogenic antigens that cause disease are streptococcal pyogenic exotoxin
(SPE) B and nephritis-associated streptococcal plasmin receptor.
 Clinical Manifestations
● 5-12 years (uncommon before age of 3 years)
● 1-2 weeks after antecedent streptococcal pharyngitis or 3-6 weeks after a
streptococcal pyoderma
● Asymptomatic microscopic hematuria with normal renal function to gross
hematuria with acute renal failure
● Various degrees of edema, hypertension and oliguria
● Peripheral edema
● Atypical presentation: those with subclinical disease and those with severe
symptoms but an absence of initial urinary abnormalities; in individuals who
present with purpuric rash.
● Acute phase resolves within 6-8 weeks
● Urinary protein excretion and hypertension normalize by 4-6 weeks after onset.
● Persistent microscopic hematuria can persist for 1-2 years
 Diagnosis
1. Urinalysis

-Red blood cell cast

-Proteinuria

-Polymorphonuclear leukocytes

2. Blood investigation

-Mild normochromic anemia (hemodilution and low grade hemolysis)

-Serum C3 level reduced, return to normal 8-10 weeks later

-Serum CH50 depressed, C4 often normal or mildly depressed

 Diagnosis
3. Throat culture report

-Positive: Evidence of prior streptococcal infection

4. Rising antibody titer to streptococcal antigens

-Antistreptolysin O titer elevated after pharyngeal infection

-Antideoxyribonuclease B level elevated after cutaneous streptococcal infection

5. Serological test for Streptococcal infection

-More sensitive than positive bacterial culture

 Diagnosis
6. MRI of brain

-for patient with severe neurological symptoms

-demonstrate Posterior Reversible Encephalopathy Syndrome on T2 weighted image

7. Chest X ray

-Indicated if there is signs of heart failure or respiratory distress

-Gallop rhythms, decreased breath sound, rales or hypoxemia

 Diagnosis
8. Renal biopsy

-considered when patient has acute renal failure, nephrotic syndromes, absence of
evidence of streptococcal infection or normal complement level

-When hematuria and proteinuria, diminished renal function and low C3 level more than
2 months after onset
 Complication
● Hypertension: Hypertensive Encephalopathy
● Acute renal dysfunction: require dialysis
● Prolonged hypertension: Intracranial bleeding
● Heart failure
● Hyperkalemia
● Hyperphosphatemia
● Hypocalcemia
● Acidosis
● Seizures
● Uremia
 Treatment
● 10 days systemic antibiotic therapy with penicillin

To treat Hypertension:

● Sodium and fluid restriction

● Diuretics
● Calcium channel blockers
● Vasodilators
● ACEI
 Differential diagnosis for acute
glomerulonephritis
● Post-streptococcal glomerulonephritis
○ Typically follows Group A B-hemolytic streptococcal infection
○ Clinical features: Hematuria, Edema, Hypertension, Renal insufficiency
occurring 1-3 weeks post infection
● IgA nephropathy (Berger disease)
○ Characterised by recurrent episodes of hematuria often concurrent with
upper respiratory infections
● Henoch-Schonlein Purpura (HSP) Nephritis
○ A small vessel vasculitis presenting with purpuric rash, abdominal pain,
arthralgia and renal involvement
○ Renal manifestations: Hematuria, Proteinuria
 Differential diagnosis for acute
glomerulonephritis
● Lupus nephritis
○ Associated with SLE
○ Presents with proteinuria, hematuria, hypertension and varying degrees
of renal dysfunction
● Membranoproliferative glomerulonephritis
○ Can be idiopathic or secondary to infectious or autoimmune diseases
○ Features include hematuria, proteinuria, low complement levels
● Rapidly progressive glomerulonephritis (RPGN)
○ A severe form of glomerulonephritis with rapid loss of renal function
○ May be associated with anti-glomerular basement membrane disease or
ANCA-associated vasculitis
Etiology of nephrotic syndrome
PAGE 16

Minimal Change
Nephrotic Syndrome
 Introduction
1. Minimal change disease (MCD) is the most
Nephrotic syndrome
common form of nephrotic syndrome
Clinical syndrome characterised
(characterised by proteinuria, edema, by massive proteinuria defined by:
hypoalbuminemia and hyperlipidemia) that ● Edema
● Hypoalbuminemia <25g/L
affecting children.
● Proteinuria >
2. 90% of children respond to corticosteroid therapy, 40mg/m2/hour or early
morning urine protein
renal biopsy usually not done at disease onset. creatinine index of > 200mg/
mmol
3. If biopsy is performed, most frequent findings are ● Hypercholesterolemia
minimal histological changes.
4. MCD is typically primary (idiopathic) but may also
be secondary to another condition.
 Definitions
Response Attainment of remission within the initial 4 weeks of corticosteroid
therapy

Remission Urine protein:creatinine ratio of <0.2

<1+ protein on urine dipstick for consecutive 3 days

Relapse Urine albumin excretion > 40 mg/m²/hour OR

urine dipstick of ≥ 2+ for 3 consecutive days.

Frequent relapse ≥ 2 relapses within 6 months of initial diagnosis OR

≥ 4 relapses within any 12 month period.

Steroid dependant ≥ 2 consecutive relapses occurring during steroid taper OR

within 14 days of the cessation of steroids.

Electron Microscope
 Clinical Features
1. More common in boys than in girls (2:1).
2. Most common in ages of 2 and 6 year.
3. Usually present as mild edema, around the eyes and lower extremities.
4. With time, edema becomes generalized, progresses into ascites, pleural
effusion and genital edema.
5. Anorexia, irritability, abdominal pain and diarrhea are common.
6. Important features: Absence of hypertension and gross hematuria.
Diagnosis
 Investigations
Tests Results

Urinalysis ● Heavy proteinuria (3+ to 4+)

● Microscopic hematuria present in 20% children

Urine protein/ creatinine ● U Pr/Cr > 0.2 on a first morning specimen excludes orthostatic
ratio proteinuria
● U Pr/Cr > 2.0 indicates nephrotic range proteinuria

Serum albumin level ● Hypoalbuminemia < 2.5 g/dL

(can go as low as 1g/dL)

Serum lipid profile ● Hyperlipidemia (Elevated triglyceride and cholesterol) due to

overcompensation by liver

Serum complement levels ● Normal C3 & C4

(To differentiate from other ● Low C3 in: Membranoproliferative glomerulonephritis, post
causes of proteinuria) infectious glomerulonephritis, SLE
 Investigations (cont)
Tests Results

Serum electrolyte ● Creatinine: Normal

● Urea: Normal/ slightly elevated
● Sodium: Low (due to depressed free water excretion/
hyperlipidemia)

Full blood count ● Increased Hb, hematocrit and platelet count

Liver function test ● Normal

Kidney USG ● Normal

● In severe edema = echogenicity and loss of corticomedullary
differentiation
 Management
1. Single dose oral corticosteroids (prednisone/ prednisolone) with 60
mg/m2/ day for 4 weeks.
2. Alternate day prednisolone 40 mg/m2 for 4 weeks, then taper over 4
weeks and stop.
3. 80% of children will achieve remission within 28 days.
4. In steroid resistant nephrotic syndrome: Should refer to paediatric
nephrologist and include renal biopsy.
(Steroid-dependant nephrotic syndrome)
 Complications
Hypovolemia Primary peritonitis
1. Due to massive loss of albumin 1. Due to hypoglobulinemia
in urine leading to decrease in 2. Features: fever, abdominal
plasma oncotic pressure pain and tenderness
2. Features: Abdominal pain, 3. Treatment: Parenteral
cold peripheries, poor pulse penicillin and third generation
volume, hypotension and cephalosporin
hemoconcentration
3. Treatment: Infuse human
albumin at 0.5 to 1.0 g/kg/dose
 Complications
Thromboembolism
1. Due to loss of antithrombin III,
thrombocytosis, increase
synthesis of clotting factor and
increase blood viscosity
2. Features: Chest pain, cough,
hemoptysis, tachypnea,
hypotension
3. Treatment: Heparin, LMW
heparin, warfarin
PAGE 29

Urinary tract
infection
 Pathophysiology
❏ The urinary tract and urine are normally sterile. Escherichia
coli, ascending from bowel (perineum) flora, accounts for
85% of first infections
❏ Other bacteria commonly causing infection include
Klebsiella, Proteus, Enterococcus, Pseudomonas, and
Enterobacter.
❏ Staphylococcus saprophyticus is associated with UTI in
some children and accounts for ≥15% of UTIs in adolescent
girl.
❏ Significant bacteriuria is defined as the presence of > 10^5
colony forming units (cfu) of a single organism per ml of
freshly voided urine
❏ Acute pyelonephritis is bacteriuria presenting clinically
with fever > 38⁰C and/or loin pain and tenderness. It carries
a higher risk of renal scarring NEPHROLOGY
❏ Acute cystitis is infection limited to the lower urinary tract
❏ Asymptomatic bacteriuria is presence of bacteriuria in the
urine in an otherwise asymptomatic child.
Clinical features
Symptoms depend on the age of the child and the site of infection. :-
● In infants and toddlers: signs and symptoms are non-specific e.g. fever, irritability,
jaundice and failure to thrive.
● UTI should be considered in children with unexplained fever.
● Infants 1 month to 2 years of age may present with feeding problems, failure to thrive,
diarrhea, vomiting, or unexplained fever. The symptoms may masquerade as
gastrointestinal illness, with colic, irritability, and crying periods.
● At 2 years of age, children begin to show the classic signs of UTI, such as urgency,
dysuria, frequency, and abdominal or back pain.
● Symptoms of lower UTI such as pain with micturition and frequency are often not
recognized before the age of two.
Diagnosis
● Accurate diagnosis is extremely important as false diagnosis of UTI would lead to
unnecessary interventions that are costly and potentially harmful.
● The diagnosis is best made with a combination of culture and urinalysis
● The quality of the urine sample is of crucial importance.
● Urine specimen transport
● If collected urine cannot be cultured within 4 hours; refrigerate specimen at 4 oC or add a
bacteriostatic agent e.g. boric acid (1.8%)
● •Use container pre-filled with boric acid and fill urine to required level.
Urine testing
● Rapid diagnosis of UTI can be made by examining the fresh urine with urinary dipstick and
microscopy. However, where possible, a fresh specimen of urine should be sent for culture
and sensitivity .
Management
Management depends on age, severity, and site of infection (upper vs lower UTI).

🔹 1. General Principles

● Prompt diagnosis and treatment are crucial to prevent renal scarring.

● Always consider pyelonephritis in febrile infants and young children, as symptoms are often
nonspecific.

🔹 2. Antimicrobial Therapy

🔸 Empirical Antibiotics (before culture results):

● Based on local antibiogram and clinical severity.

Management
Age / Condition Route Common Drugs

Infants <3 months or very ill IV Ampicillin + Gentamicin / Cefotaxime

>3 months, toxic/septic IV Ceftriaxone / Cefotaxime

Stable children >3 months Oral Cefixime / Amoxicillin-clavulanate / Nitrofurantoin (for

cystitis only)

Duration:

● Lower UTI (Cystitis): 5–7 days

● Upper UTI (Pyelonephritis): 10–14 days

Management
3. Supportive Care
Imaging Study Indication
● Adequate hydration
Renal & bladder ultrasound All infants with first febrile UTI
(RBUS)
● Antipyretics (e.g., paracetamol for fever) (esp. <2 yrs)

MCUG (Micturating If RBUS abnormal, recurrent

● Monitor for response within 48 hours Cystourethrogram)
UTI, or atypical UTI
🔹 4. Imaging & Follow-up DMSA scan 6 months after UTI to assess
renal scarring
Recommended to detect underlying urinary
tract abnormalities.
Management
5. Prophylaxis

Indicated in:

● Recurrent UTI

● Vesicoureteral reflux (VUR) grade III–V

● Obstructive uropathy

Common drugs: Nitrofurantoin, Trimethoprim (low-dose, nightly)

🔹 6. Surgery

● For correctable anomalies (e.g., posterior urethral valves, VUR, obstruction)

 Complications
Complication Description

🔸 Renal scarring Most serious long-term consequence; may lead to hypertension or CKD

🔸 Hypertension Due to loss of renal parenchyma and scarring

🔸 Proteinuria Marker of glomerular damage due to scarring

🔸 Chronic kidney disease (CKD) Recurrent UTI or severe scarring in both kidneys can reduce function

🔸 Vesicoureteral reflux (VUR) Common underlying anomaly; predisposes to recurrent UTI and scarring

🔸 Sepsis Especially in neonates and infants; can be life-threatening

🔸 Failure to thrive Due to chronic illness in infants

🔸 Bladder dysfunction Especially with neurogenic bladder or dysfunctional voiding

🔸 Recurrent UTIs Due to untreated predisposing factors or poor hygiene

PAGE 39

Urologic
Imaging for
children with UTI
1. Renal and Bladder Ultrasound(RBUS)
To evaluate kidney size, shape, hydronephrosis and bladder anatomy

Ultrasound of left kidney

demonstrating mild
hydronephrosis
2. Voiding Cystourethrogram(VCUG)
To detect vesicoureteral reflux(VUR) and posterior urethral valves

Vesicoureteral
reflux
3. DMSA Scan(Dimercaptosuccinic Acid)
To detect renal scarring and pyelonephritis

DMSA scan image reveals a

cold spot in the upper pole of
the right kidney due to renal
scarring in a child with a
history of febrile urinary tract
infections
PAGE 43

LO 7:
Vesicoureteral
Reflux
 Etiology
- Developmental anomaly of vesicoureteric junctions that causes retrograde flow of urine from the
bladder up the ureter or even into the kidney
- VUR exposes kidney to hydrodynamic pressure during voiding and increases likelihood of renal
infection due to incomplete emptying of the ureter and bladder.
- VUR is often associated with:

1. Reflux 3. Duplication of
5. Cystitis or
nephropathy the ureters
Acquired
bladder
-Development - May obstruct 4. Neurogenic
obstruction
and progression 2. Renal the upper bladder
of renal scarring dysplasia collecting
-VUR results
-If VUR is system -Accompanied
from increased
associated with -Associated with -The ureter by VUR in up to
intravesicular
UTI or congenital VUR draining the 50% of affected
pressure when
obstruction lower pole of a children
the bladder
-Incidence is duplicated renal
outlet is
higher in unit often has
obstructed
recurrent UTI VUR
 Classification
Grade I : Into a nondilated ureter

Grade II : Into the pelvic and calyces without

dilation

Grade III : Mild to moderate dilation of the

ureter, renal pelvis, and calyces with minimal
blunting of the fornices

Grade IV : Moderate ureteral tortuosity and

dilation of the pelvis and calyces

Grade V : Gross dilation of the ureter, pelvis,

calyces; loss of papillary impression; and
ureteral tortuosity
 Clinical Features
The younger the patient with UTI, the more likely VUR is present

No clinical signs reliably differentiate children with UTI with or without VUR

Clinical Manifestations of UTI

Infants (1m to 2y) >2 years - shows classical

Neonates signs of UTI
1. Feeding problems
1. Failure to thrive 2. FTT I 1. Urgency
2. Feeding problems 3. Diarrhea 2. Dysuria
3. Fever 4. Vomiting 3. Frequency
5. Unexplained fever 4. Abdominal / Back
pain
Diagnosis
● Renal ultrasound is the best study to evaluate urinary tract in children.
● A voiding CystoUrethrogram(VCUG) or radionuclide cystogram (NCG) peformed to detect urethral
or bladder anomalies.
● VCUG should also be performed if there is a recurrence of a febrile UTI.
● Incidence of renal scarring in patients with low-grade VUR is low (15%) and increases with grade IV
or V reflux (65%)
● Grade I and II VUR is likely revolve without surgical intervention but VUR <50% grade IV or V.
● Nuclear renal scanning best identifies renal scars.
Treatment
● Controversy remains about whether long-term prophylactic antibiotic therapy
(trimethoprim-sulfamethoxazole or nitrofurantion) is indicated to mild to moderate VUR.
● It is optional in this population and maybe useful in children with high grade of VUR or recurrent
symptomatic UTI.
● Indications of surgical repair of VUR are options now include instillation of dextranomer/hyaluronic
acid copolymer into bladder wall(Deflux procedure),minimally invasive correction of mild to
moderate VUR.