Nephrotic Syndrome

and Acute Nephritic

Syndrome
CBD(4)
supervised by
Dr Osama Safder
presented by
Maryam Bajaiffer – Ahad Taj – Estabraq Alomran – Jomana Nasser
 Case (1)
10 year old Myanmar boy known case of
______ and on _______ presented to the ER with
history of edema for 5 days.
Generalized edema Localized edema
• Cardiac (CHF) • Traumatic (Fracture, Ligament
• Renal (Nephrotic syndrome, Acute tears)
nephritis) • Inflammatory (Abscess, Cellulitis)
• Hepatic (Cirrhosis, hepatitis, liver • Lymphatic (Mets causing pressure
disease) on LN)
• Allergic (certain foods or • Venous (Venous thrombosis,
medications) varicose veins)
• Nutritional (protein malnutrition)
• Drug induced (steroids, Insulin)
Mohammed is a 10 year old boy from Myanmar known case of
______ and on _______ presented to the ER with history of generalized
edema for 5 days.
Positive history of vomiting, diarrhea, RUQ pain, with cough and
subjective fever, for 3 days
Patient started to have puffy eyes, scrotal edema, abdominal
distention, progressive for the past 5 days
Oliguria, dark urine in the last 2 days

No history of SOB
No history of jaundice or eating out
Other systemic review unremarkable
No known allergies to medications or foods
He is compliant to medications, following up in outpatient
department
Antenatal history: product of full term, spontaneous vaginal
deliver of uncomplicated pregnancy.
Diagnosed at age of 7 months when presented with
generalized edema.
Multiple admissions as relapses, last one was a year ago.
Diet: family diet.
Vaccines: vaccinated fully, no extra vaccines
Development: up to age, attending school with good performance
Family history: has other 6 healthy siblings, no consanguinity, no
similar illness in the family.
Social history: lives in kilo 14, small apartment, father is a
salesman, mother is a stay-at home mom, low socioeconomic
status.
 Clinical Presentation

Vomiting

cough

Abdominal
distension

RUQ pain

diarrhea
Generalized edema history DDx:
CHF: Failure to thrive, SOB, cough, Hx of heart disease
Nephritic syndrome: tea like urine, low urine output, puffiness around the
eyes
Nephrotic syndrome: puffiness around eyes, frothy urine, abdominal
distention
Liver damage, acute hepatitis : jaundice, dark urine, black tarry stool,
pain/lump in abdomen, itching, petechiae, bleeding tendency
Allergic: lips, eyelids, face involvement, urticaria, wheezing
Malnutrition: Anorexia, lethargy, diarrhea, vomiting, decreased growth,
frequent infections, anemia (palpitations, fatigue)
Drug induced: Prednisolone decreased growth, central fat, peripheral
edema, increased risk of infection, hypertension
 Examination

Vitals:
– RR: 20 bpm (N:18– 25)
– Temp:37 C oral (N:35.5 – 37.5)
– BP: 154/91 mmHg (N: SBP: 102-120
DBP: 61-80 mmHg)
– HR: 72 bpm brachial (N: 75 – 118)
– SpO2 : 100
Growth Parameters
– Weight: 47.7 kg
– Height: 150 cm
– BMI: 21.2
 Examination

Patient lying comfortably on bed, alert, conscious, not in

distress not jaundiced. Periorbital edema and cushioned
face with hypertrichosis +bilateral lower limb non-pitting
edema up to the thighs.
RS: BEAE, clear, no crepitation
CVS: S1+S2, no murmurs
GIT: distended abdomen, not tender, shifting dullness, no fluid
thrill
Genitalia: scrotal and penile edema
Neuro: intact, normotonia, power 5/5, normoreflexia
Can We Narrow Down
Our Ddx ?
Generalized Edema Examination DDx:
CHF: delayed growth, tachypnea, tachycardia, Gallop
rhythm, cardiomegaly, hepatomegaly, lung crepitation,
pitting edema
Nephrotic: periorbital edema, ascites, sacral edema
(infants), lower limb edema (child)
Nephritic: periorbital edema, hypertension( decreased
vision, headache, heart failure)
Cirrhosis: hepatomegaly, ascites, astrexis, altered LOC,
pitting edema
Malnutrition: delayed growth
 Investigation

Initial investigations Subsequent Investigations

Urinalysis Complement; C3, C4

CBC Renal biopsy
U&E Imaging studies
Lipid profile – X-ray
– Ultrasound
PT/PTT
LFT
 Investigation

Urea (BUN): ↓ 2.0 mmol/L (RR: 2.5 – 6.4 mmol/L)

Creatinine: ↓ 23 umol/L (RR: 53 - 115 umol/L)
Calcium: ↓ 1.95 mmol/L (RR: 2.12-2.52mmol/L)
Albumin: ↓ 19 g/L (RR:40.2-47.6 g/L)
Sodium: 129 mEq/L (RR:135-145 mEq/L)
WBC: 10.33 K/uL (RR: 4.5-13.5 K/uL)
RBC: 4.79 M/uL (RR: 4 – 5.4 M/uL)
Hb: 13.5 g/dL (12 – 15 g/dL)
 Investigation

LFT Urine analysis:

Protein:2+ (RR: negative/0)
PT: normal 11.1 s (RR: 11– 14 s) Color: yellow
APTT: ↑ 43.2 s (RR: 29 – 40 s) WBC: 1 (RR: 2 – 5 hpf)
Total protein: ↓ 42.3 Specific gravity: ↑ 1.015
Alkaline Phosphatase:↓ 112 (RR: 1.000 – 1.030)
Albumin:↓g/L(RR:40.2-47.6 g/L) pH: 5.0 (RR: 4.5 – 8)
AST: ↓ 5 (RR: 10 – 40 U/L)
ALP: ↓ 6 (RR: 7 – 56 U/L)
GGT: 11 U/L (RR: 9 – 48 U/L)
 Investigation

• Lipid profile:
Cholesterol: 4.77 mmol/L (RR: 0 – 5.2 mmol/L)
Triglycerides: 0.77 mmol/L (RR: 0.3 – 2.3 mmol/L)
HDL: 1.36 mmol/L (RR:0.3– 2.3 mmol/L)
LDL: 2.82 mmol/L (RR: 0 - 3.57 mmol/L)

• Complement
C3: 0.91 g/L (RR:0.75 – 1.65 g/L)
C4: 0.275 g/L (RR: 0.2 – 0.6 g/L)
 Investigation

Radiological findings
U/S: Kidney Biopsy

Kidney biopsy indications

Atypical age (less than 1 year and more than 10 years)
Atypical response (steroid resistant)
Atypical lab (gross hematuria)
Hypertension and renal failure

Chest x-ray: pleural effusion

Urine Analysis:

Protein:2+(RR: negative/0) and 3+ next day

Color: yellow
WBC: 1 (RR: 2 – 5 hpf)
Specific gravity: 1.015 (RR: 1.000 – 1.030)
pH: 5.0 (RR: 4.5 – 8)
Approach To Patient With
Proteinuria:

The normal urinary protein loss is

<4 mg/m2/hr or <100 mg/m2/day
Nephrotic proteinuria:
>40 mg/m2/hr or >1000 mg/m2/day
Urine Dipstick Analysis:
Dipstick is from yellow to green
Yellow = no protein  
Trace = 5-20 mg/dL
4 levels of green, the more protein the darker the green
1+ = 30 mg/dL
2+ = 100 mg/dL
3+ = 300 mg/dL
4+ = Greater than 2000 mg/dL
24-hour Urine Collection:

Early morning urine sample

Not practical
Normal value: <100 mg/m2/day
Nephrotic range proteinuria:
>1000m2/day
Protein To Creatinine Ratio:
Early morning urine sample
Normal value: <0.2 if >2 years old
Subnephrotic range: 0.2 – 2
Nephrotic range proteinuria: >2
 Random urine dipstick
+ve for proteinuria

1st morning sample –ve 1st morning sample +ve

Dipstick Edema No edema

+1 +2

P:Cr >2 Fever,

P:Cr < 1
P:Cr <2 illness,
exercise

Orthostati 24 hr urine
Nephrotic > Transient
c
syndrome 1g/m2/da proteinuri
proteinuri
y a
a
NEPHROTIC SYNDROME
 Proteinuria Hyperlipidemia
• Hypercholestriemia
• Nephrotic proteinuria
• > 250 mg / dL
• > 40 mg/ m2/ hour
•  Xanthelsma &
• or 1g / m2/ day [24
Xanthoma
hours]
•  frothy urine
Nephrotic
Syndrome
Hypoproteinemia Edema
• Mainly serum albumin
• Hypoalbuminaemia
• < 3 g / dL
 Pathophysiology

Increased glomerular permeability –

Resultant massive
alteration in the normal glomerular Plasma oncotic pressure; diminished ;
proteinuria leads to
cellar and basement membrane leading to fluid shifts from vascular
decreased serum
barrier that restrict filtration of interstitial compartment and plasma
protein, [albumin]
serum protein volume contraction
.
Edema results from reduction in effective
Hypoproteinemia:
circulating blood volume and increase in
stimulate hepatic
tubular sodium chloride reabsorption
lipoprotein synthesis,
secondary to activation of RAAS
leading to elevated
serum lipids [cholesterol
and triglycerides]
 hypoalbuminaemia

Reduced
intravascular oncotic
pressure

Loss of fluid into

interstitial space

Increased albumin production Reduced plasma volume

and lipoprotein synthesis

Increased Decrease
Increased serum TG& LDL aldosterone renal
function

Lipiduria Salt & water retention edema

Causes

95 % idiopathic
5 % : secondary
 Histological classification

Minimal change disease Focal segmental Membranous

[MCD] glomerulosclerosis Glomerulonephropathy

• LM: normal • LM & EM: segmental & focal

• LM & EM: uniform thickening of
• IF: IgM in mesangial cells sclerosis
GMB & focal sclerosis as the
• EM: loss of podocytes foot • Steroid responsive < 20 %
disease progress
process
• IF: IgG & C3
• Selective proteinuria
• Steroid responsive > 95%
 Complications

Hypovolemia Intra-vascular thrombosis

 delayed capillary refill Hypovolemia  increase viscosity ; increased
platelet adhesiveness & coagulation factors
 tachycardia Decreased natural anticoagulants ; anti
 abdominal pain thrombin III, protein C

Acute renal failure (nephrotic crisis) Infections

Severe hypovolemia : decrease renal blood flow Loss of complement regulator &
immunoglobulin , immunosuppressive
(pre-renal failure)
therapy
Steroid resistant nephrotic syndrome Common infections: capsulated bacteria

Hypertension
Malnutrition
 Urinalysis
For diagnosis
Biochemical

CBC
Investigation

Workup before Urine microscopy

starting therapy & cultures

Lupus antibody
serology

Age Atypical

Gross hematuria
• Age:
Before treatment
• < 3 mo:
Renal failure
congenital
Renal biopsy Indications Low complement
• 3-12 mo:
infantile
Steroid • Response
resistance
After treatment • Lab:
Relapse • Renal failure
• Gross hematuria
• Low
complement
 Fever
Transient
Exercise
proteinuria

Nephrotic
+ Edema
syndrome

+ve
Morning [am]
24 hr urine
- Edema > 1 g / m / 24 hr
collection
+ Dipstick
Nephrotic syndrome
Evening [pm] Orthostatic
 Management

Supportive Specific
treatment treatment

Treatment of Treatment of
Diet Immunization Prednisone
edema complication

Thrombo-
Long-term
Salt restriction Diuretics Infection Hypertension embolic Varicella
steroids
episodes

Increase Fluid Calcium 250

ACEI antibiotics ACEI Pneumococcal
protein intake management mg

Prevent
H. Albumin
CCB immobilizatio Vitamin D 125 Neisseria
infusion
n

Antiplatelet
HiB
(aspirin)

Anticoagulant Influenza
(LMWH) (annually)

No role for anti-thrombotic and anti-lipidemic agents in nephrotic

Treatment:
glucocortcosteroid such as prednisone are used.
Rituximab, an antibody against B-cells, has proved an effective steroid-
sparing agent in children with steroid-dependent idiopathic nephrotic
syndrome, also be used in children with steroid-resistant disease.

Long-Term Monitoring
Ongoing use and adjustment of diuretics and angiotensin antagonists
are done according to the amount of edema and proteinuria that a patient
has.
Follow-up care in patients with nephrotic syndrome also includes
immunizations and monitoring for corticosteroid toxicity.
Oral Prednisolone should be started at:
– 60 mg/ m²/day everyday for 4 – 6 weeks

– 40 mg/m²/every alternate morning for 4 – 6 weeks

– Gradual decrease of Prednisolone dose over next 10 - 12weeks

– Duration: 24 weeks (6months)

 60 mg/ m²/day 4-6 weeks

Respond 40mg/ m²/day 4 – 6 weeks

Steroid (Prednisolone)

Steroid-sensitive Decrease dose

nephrotic syndrome 10-12 weeks
gradually

Cyclosporine
60 mg/ m²/day
4 weeks FSGS ACEI

+/- diuretics
No response Resistance
Atypical Age

Atypical
Renal biopsy
response

Atypical Lab
Steroid sensitive nephrotic syndrome
Relapse: Recurrence of significant proteinuria: +2 or more in 3 consecutive
days
Infrequent relapse
– Once yearly (short course of treatment )
– 60 mg/m2 or 2 mg/kg every day from 2 weeks.
– then decrease the dose to 40 mg/m2 giving on alternative day from 4 weeks.
– Then gradually decrease the dose over 4-6 weeks.

Frequent relapsing nephrotic syndrome:

– 2 Relapses or more within 6 months or 4 Relapses or more within 12 months

Steroid dependent nephrotic syndrome:

– It’s a relapse while patient on alternative daily steroids or within 14 days of
stopping steroids
– 60 mg/m2 or 2 mg/kg every day from 2 weeks.
– then decrease the dose to 40 mg/m2 giving on alternative day from 4 weeks.
– Then give the patient a constant dose for one / one & half year.
– If still relapsing then we consider steroid sparing agents
Steroid Resistant Nephrotic Syndrome :
“No response to steroids within the 1st 4 weeks of 1st presentation”

Methylprednisolone + cyclophosphamide (steroid-sparing agent)

Steroid therapy +
methylprednisolone
kidney biopsy & genetic testing to avoid excess glucocorticoid
toxicity
steroid sparing medications (cyclosporine)
Diuretics
 Side effect Drugs
Moon face, psychosis, HTN, DM, frequent infection,
osteoporosis, peptic ulcer, eye manifestaion. Steroid

alopecia, infertility, hemorrhagic cystitis, leukopenia. Cyclophosphamide

GI disturbance, aplastic anemia, Mycophenolate Mofetil

(MMF )
hypertension, nephrotoxic, hyperkalemia, acidosis, Cyclosporine
hypomagnesaemia, hyperlipidemia, gall bladder stone, fine
tremor

leukopenia, cutaneous vasculitis, CNS manifestation. Levamisole

 Management for case:

• Albumin Human 20% Vial 100 mL

• Captopril 25 mg tablet
• ACEI
Enalapril Maleate 10 mg tablet
• Chemo for steroid resistant nephrotic syndrome (Rituximab) Anti-neoplastic, monoclonal antibo
• Furosemide 20mg/2mL Ampule diuretics
• Omeprazole 10 mg
• Loratadine 10mg tablet
• Nifedipine 10 mg capsule
• Amlodipine Besilate 5 mg
CCB
• Paracetemol 500 mg
• Prednisolone 20 mg Steroids
 Case (2)
History:
3 years Somali female patient presented to the ER on 13-Aug complaining of generalized body
swelling started only 3 days before admission .it was associated with vomiting whatever she ate , foody
content which is neither projectile nor bloody .
One month before that she started complaining of on and off fever associated with Oliguria, frothy red
urine with unusual smell .it wasn't associated with weight loss or night sweat
She has no history of URTI or contact with sick patient
7 months back she had fever ,skin rashes in her lower limbs, oral fungal infection ,lower limb edema
and abdominal distention that treated as local skin infection but one week after she didn’t improve so
she went back to the hospital and investigations were done .
She received blood due to sever anemia and started on oral AB 14 days / month
At age of 8 months she had right inguinal abscess that investigated for TB but was negative ..
She had surgical biopsy of axillary lymph node at age of 4 months
Patient has chronic anemia and had multiple blood transfusions. last one was 8 months ago
There is Positive consanguinity but there is no family history of the same complain ,autoimmune disease
or other renal disease
she has no known allergies .
she took her vaccines tell 1 year old .
developmentally up to age
She was bottle and breast fed since she was born and started solids on 4 months with no dietary
restrictions
Examination:
On examination:
Patient looked pale, not on distress ,had generalized edema (orbital, ascites and
bilateral lower limbs and sacral area ) she has submandibular, axillary and inguinal
lymph node enlargement .she also had oral ulcers and lower limbs rash which is purple
in color ,itchy ,not crusty or bleeding .
No other abnormal findings
GCS:15/15
CVS: normal S1,s2 +hemic murmer with delayed capillary refel
RS : normal
CNS:normal
ABD:normal

Vitals :
BP:123/72(high)
RR:28
Temp:37
HR:110
 Hematuria

Non glomerular glomerular

-could be painful -painless

-bright red -dark red (cola or tea
like)
-no cast (microscopic)
-positive cast
(microscopic)
 Hematuria

Glomerular Non
cause Glomerular

Immunological Structural Infections

IgA Systemic Thin Alport

nephropat PSGN cause ex: basement syndrome
hy SLE membrane Symptoms
(most (x linked )
,vasculitis disease of
(recurrent) common) History of
or (AD) infections
History of henoch- hearing
First according
pharyngiti schonlein loss in
relative to the age
s or purpura boys
dermatitis history
 Non glomerular causes

LUT
Tubular -trauma Increase
Non
(mainly microscopic -infections pathologic hemolysis Increase in
with history of HUS bleeding
al : tendency
polyuria ) Rhabdomyolysis
Food
-infection Drugs
-structural Urate
-trauma crystals in
-sickle cell anemia infant
Hematuria Approach:
Urinalysis

Negative Positive
for blood for blood

Non pathological cause ex: Urine microscopy

food ,drugs

Minimal RBCs RBCs Confirmed

Could be hemolytic or
rhabdomyolysis
CBC Liver function Calcium low
WBC 17.11 HIL index 113 Phosphate 2.7(high)
RBC 2.46(low) Aspartate amino 28
transferase Total protien 77
Hb 4.7(low) Albumin 19(low)
Alanine amino 7(low)
HCT 15.8(low) transferase
Alkaline phosphate 109(low)
MCV 64.2(low) Gamma glutamyl 6
transferase
PLT 542(high)
magnesium 0.64 (low)
Total bilirubin 3
Basophils 0.03
Albumin 16.8(lo
neutrophils 9.8(high) w) IgA high
Lymphocytes 6.3 PT 13 IgG high
Eosinophil 0.12 APTT 34.4 IgM high
U&E
sodium 131(low)
Potassium 5.4(high)
Chloride 104
Urea 32(high)
creatinine 360(high)
Urine analysis :

High protein (2.99)

Low creatinine (2500)
Negative culture
ACUTE NEPHRITIC
SYNDROME
Acute Nephritic Syndrome :
a group of symptoms that occur with some disorders
that cause swelling and inflammation of the glomeruli
in the kidney, or glomerulonephritis

often caused by an immune response triggered by an

infection or other diseases

Poststreptococcal glomerulonephritis (PSGN) is the

most common form of acute GN
Poststreptococcal
Glomerulonephritis
follows infection with nephritogenic strain group A-𝛃
hemolytic streptococci causing throat infection or skin
infection
diagnosed by evidence of streptococcal infection :
- culture
- raised ASO / anti DNAse B titres
- low complement C3 levels that return to normal after 3-4 weeks
more common in boys 2-12 yeas of age
after 2 weeks of streptococcal pharyngitis or
6 weeks of skin infection
 PSGN Pathogenesis

deposited in glomerular
streptococcal latent Antigen + Antibody + acute
antibodies basement membrane
infection period C3 complexes (subepithelial humps) inflammation

glomerular impaired glomerular

cells
capillaries glomerular endothelial
proliferation
narrowing blood flow damage

↓glomerular - hematuria and maybe proteinuria

++ JGA
filtration rate
- oliguria
- ++RAAS system > hypertension
- fluid retention >
hypervolemia > oedema
PSGN Pathogenesis
 PSGN Clinical Presentation
hematuria and proteinuria
 Hematuria could be marcoscopic
(blood in the urine visible to the naked
eye) or microscopic (more than 5 RBCs
per high power field per per freshly
voided and centrifuged urine)
oliguria and volume overload
hypertension ( most common
complication appears as headache,
heart failure, decrease in vision )
peripheral edema (periorbital)

 some cases are asymptomatic and

discovered accidentally on routine
urinalysis
Complications

maybe the presenting event

hypertensive encephalopathy (due to hypertension)

heart failure (due to hypertension or hypervolemia)
acute renal failure
Investigation
Urine Analysis ( RBC, RBC casts, low leukocytes, protein )
Renal Biopsy for prognosis
Kidney function (urea and creatinine from mild renal
failure)
Electrolytes (sodium, potassium, calcium, phosphate)
Blood gases for acidosis from renal failure
Complements (PSGN affects only C3, not C4, so you will see
only decrease C3)
throat swab and skin culture
ASO titer or Anti-DNAse 𝛃 for previous
streptococcal infection
Management
bed rest
penicillin course ( in case of positive culture result )
diet ( salt restriction )
monitor urine output, blood pressure, electrolyte
if they have hypertension, best treatment for it in PSGN
is furosemide -lasix- (because they have oliguria and
the best management for it is diuretics)
 Reference
Nelson Essentials of pediatrics, 7th edition
Illustrated, pediatrics, 5th edition
Practical aspects of pediatrics, 7th edition
Dr Osama Safder’s notes