It is a clinical syndrome of:
1. Heavy proteinuria
↓ serum albumin < 2.5 g/dL
Protein:Creatinine > 200mg/mmol
> 250 mg/dL
Uncommon: 3 new cases per 100,000 child population
Higher incidence: 16 new cases per 100,000 child population
No available data, it is thought to have higher incidence than in the west
Minimal Change Disease
most common (70-80%)
M:F = 2:1
< 7 years old
steroid-sensitive nephrotic syndrome
do not progress to renal failure
often precipitated by respiratory infections
age between 1 and 10 years
no macroscopic haematuria
normal blood pressure
normal complement levels
normal renal function.
- under fill theory: hypoalbuminemia
- over fill theory:↑ tubular NaClreabsorption secondary to RAAS -> intravascular expansion -> fluid shift following pressure gradient
- hypopratenemia -> hepatic lipoprotein synthesis
-> ↑serum lipid (cholesterol, lipoprotein) -> lipid
Spontaneous bacterial peritonitis, cellulitis, bacteriemia (S.pneumoniae, E.coli)
Steroid and immunosuppressant toxicity
abdominal pain and may feel faint, cold peripheries, poor pulse volume, hypotension, and haemoconcentration.
A low urinary sodium (<20mmol/L) and a high packed cell volume
hypercoagulable state due to urinary losses of antithrombin, thrombocytosis
exacerbated by steroid therapy
increased synthesis of clotting factors
increased blood viscosity from the raised haematocrit,
This is usually arterial and may affect the brain, limbs and splanchnic circulation
Acute renal failure (rare)
Sudden onset of dependent pitting oedema
- scrotal or vulva
- ankle or leg
- abdominal pain
Diarrhea (dt intestinal oedema)
Respiratory distress (dtpulm. oedema)
First time or relapse???
History of edema noted on awakening in the morning or sudden swelling??
Initiating factor? (bee sting)
Weight gain (edema)
Pass medical and drug history: recent illness, allergies, asthma
Assessment of hydration status identifies fluid imbalances (dehydration, overhydration)
Blood pressure: hypertension
Systemic lupus erythematosus (malar rash)
Rales heard on lung auscultation suggest extravascular fluid from overload or hypoalbuminemia
Palpation and percussion of the abdomen may reveal ascites or masses
Liver enlargement is present in several multisystem diseases (systemic lupus erythematosus, infections, polycystic disease) and in glomerulosclerosis
Other causes of hypoalbuminaemia
Postural orthostatic proteinuria
Proteinuria +1> on 2/3 random urine sample (Dipstick)
P:C (> 200mg/mmol) (early morning)
C3 level ( sensitive n specific if other than MCD)
Full blood count: HCT, WBC
Renal profile: normal in MCD
Serum albumin: <25g/dL
Urinalysis and quantification for urinary protein excretion
abundant hyaline cast
Haematuria (other thn MCD)
Na+ <10mmol/L in hypovolaemia
complement levels: decrease suggest other thn MCD
Antistreptolysin O titre and throat swab
Hepatitis B antigen
DEFINITION FOR DX & TX OF IDIOPATHIC NS
Urinary protein excretion < 4 mg/m2/hour or urine dipstix nil/trace for 3 consecutive days.
Urinary protein excretion > 40 mg/m2/hour or urine dipstix ++ or more for 3 consecutive days.
Two or more relapses within 6 months of initial response or four or more relapses within any 12 month period.
Two consecutive relapses occurring during the period of steroid taper or within 14 days of its cessation.
Normalization of proteinuria within 4 weeks after start of standard initial therapy with daily oral predinisolone
Failure to achieve remission in spite of 4 weeks of standard prednisolone therapy.
Prednisolone regime for initial dx:
60 mg/m2/day (max 80mg/day) for 4 weeks
40 mg/m2/48 hr (max 60mg/dose) for further 4 weeks
Prednisolone regime for relapses:
60 mg/m2/day (max 80mg/day) until remission
40 mg/m2/48 hr for 4 weeks
Frequent relapse or steroid dependent:
Long term low dose prednisolone for 3-6 months
SCHEMA OF TREATMENT OF IDIOPATHIC NEPHROTIC SYNDROME
1. Nephrotic Syndrome
Prednisolone 60 mg/m2/day (max 80/day) for 4 week
Response No Response
Prednisolone 40 mg/m2/48 hours for 4 weeks
*Discontinue *Steroid taper at 25% monthly over 4 months
Prednisolone 60 mg/m2/day (max 80 mg/day) till remission,
then 40 mg/m2/48 hours for 4 weeks and discontinue.
3. Frequent Relapses
Reinduce as for (2) above, then taper and keep low dose alternate day
prednisolone at 0.1 - 0.5 mg/kg/dose for 6 months.
4. Relapse on prednisolone
As for (3) if not steroid toxic,
consider cyclophosphamide (cumulative dose 168 mg/kg) if steroid toxic.
5. Relapses post cyclophosphamide
As for (2) and (3) if not steroid toxic.
If steroid toxic, refer paediatricnephrologist to consider
a). second course cyclophosphamide or
b). cyclosporine therapy.
blood pressure control : ACEi (captopril, enalapril), angiotensin II receptor antagonist
Cyclosporin, tacrolimus, mycophenolatemofetil
Indications for renal biopsy
A renal biopsy is also NOT required prior to cytotoxictherapy
Steroid resistant nephroticsyndrome
Stunting of growth
Severe cushingoid features
behavioural changes, a rounded face, central obesity and the tendency to bruise more easily, hirsutism
Recurrent infection dt low immunity
Mx of oedematous state
Bed rest to be avoided as there is a tendency of hrpercoagulability
Dietary advice: no added salt, normal protein with adequate calories
Prophylactic antibiotics: oral penicillin particularly in during relapse with gross oedema
Hypovolaemia: infuse salt poor albumin or 5% albumin, plasma protein derivatives or human plasma
Infection: parenteral penicillin and a third generation cephalosporin (in primary peritonitis)
If exposed to chickenpox and measles varicella-zoster immunoglobulin (VZIG) should be given within 72 hours after exposure to chickenpox / single dose of intravenous immunoglobulin.
Thrombosis : Warfarin, low-dose aspirin, and dipyridamole all have been used to minimize the risk of clots.
URINE ALBUMIN MONITORING
It is advocated that monitoring of urine albumin excretion be done regularly either at home with urinary dipstix or at the nearest health centre.
Parents and school teachers should be provided with information regarding the disease which includes:
Advice and precaution of infection
Danger of sudden steroid withdrawal (adrenal crisis)
While the child is on corticosteroid treatment and within 6 weeks after its cessation, only killed vaccines may be safely be administered to the child. Live vaccines can be administered 6 weeks after cessation of corticosteroid therapy
Acute nephritic syndrome
NUR AMIRA BINTI MOHD ASRI
A 7 year old Malay boy was admitted 3 days ago with the chief complaints of facial puffiness and passing smokey and frothy urine for 1 week. The facial puffiness initially started off as periorbitaloedema which then progressed to involve the entire face within a week. Urinary output was also decreased. He also complaint of fever for one week which was of low grade, intermittent with no chills and rigor. There is also presence of an erythematous itchy skin lesion on his right elbow which was first noticed 2 weeks back. There is no history of sore throat, flu, blood transfusion, nausea, and vomiting, rashes, dyspnoea and chest pain. General examinations revealed pallor, high blood pressure of 139/96 mmHg, and an erythmatous scaly circular skin lesion on his right elbow. Urine biochemistry revealed protein 3+, RBC 4+. Blood urea was raised to 500 umol/L.
It is a clinical complex, usually acute onset, characterized by:
oedemaeg facial puffiness
Microscopic/macroscopic haematuria (tea-coloured urine)
Oligouria (decreased urine output)
Azotemia/uremia (excess urea in urine)
The lesions that cause nephritic syndrome have in common proliferation of cells within in glomeruli, accompanied by a leukocytic infiltration.
This inflammatory reaction injures the capillary walls, permitting escape of RBC into the urine(hematuria) , and induced hemodynamics changes that lead to a reduction in GFR which are manifested clinically by oligouria, reciprocal fluid retention and azotemia
Hypertension is the result of the fluid retention by kidney secretion of renin.
The commonest cause of nephritic syndrome
Usually followed a nephritogenic streptococcal pharyngitis or impetigo with a strain of group A beta-hemolytic streptococci
Occurs most frequently in children 2 to 12 years old
Boys are frequently affected
This is diagnosed by evidence of a recent streptococcal infection (culture of the organism, raised ASOT) and low complement C3 levels, that return to normal after 6-8 weeks
Long term prognosis is good
Epidemiology of post acute strep GN
121 of the 124 nephritis patients had poststreptococcal infection.
(Department of paediatrics, HUSM, July 1987-June 1988)
Globally-incidence has decreased in the past 3 decades
Despite that,epidemic cases in some poor and rural communities
Immune complex formation +deposited in GBM
Complement system activated
Low serum complement
Capillary lumen narrowed
Glomerular blood flow decreased
Distal sodium reabsorption
Retention of water and sodium
Edema and hypertension
Blood volume increased
It is a systemic syndrome involving the skin (purpuric rash), gastrointestinal tract (abdominal pain, joints (athritis), and kidney
Usually occurs between the ages of 3-10 years olds
Twice as common in boys
peaks during winter months
Is often preceded by an upper respiratory infection
Unknown cause however it is postulated that genetic predisposition and antigen exposure increase circulating lgA levels.
By immunofluorescence and electron microscopy the findings may be similar to those of IgAN
The combination of
Skin rashes(symmetrical distributed over the buttocks,extensor surface of arms and legs and the ankles.
Athralgia (knees and ankles)
Colicky abdominal pain, GI petechiae,hematemesis, melaena, intussusception
Systemic lupus erythematosus (SLE)
Is an autoimmune disease that presents mainly in adolescent girls and young women(5% in childhood girl, rare in children younger than 9 yo, equal gender distribution in children)
Multisystem disorder of unknown etiology characterized by the production of large amounts of circulating antibodies due to loss of T lymphocytes control on B lymphocytes which leads to autoantibody production
Presence of multiple antibodies including antibodies to double-stranded DNA .
Criteria for diagnosis of SLE
Malar rash (butterfly rash)
Oral and nasopharyngeal ulcers
Pleuritis and pericarditis
Non erosive arthritis ( more than 2 joints with effusion and tenderness.
Protenuria(>500mg/24 hrs) or RBC cellular cast in urine
Evidence of presence of antiphospholipid antibodies
Affects children and young adults
Begins as an episode of gross hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection.
Is one the most common causes of recurrent microscopic or gross hematuria and is the most common glomerular disease revealed by renal biopsy
The pathology hallmark is the deposition of lgA in the mesangium
Prognosis is good in children
immunofluorescence with anti-IgA antibodies deposited in the mesangium
The commonest familial nephritis is Alport’s syndrome
X-linked recessive disorder
Is associated with nerve deafness and ocular defect
The mother may have hematuria
Can progress to end-stage renal failure by early adult life in males.
Basic workup of a child with hematuria
Physical examination-height,weight,bloodpressure,funduscopy,presence or absence of abdominal mass,skinappearance,genitalia,edema,complete physical examination.
Laboratory-urinalysis (includingmicroscopic examination and RBC morphology), urine culture, complete blood count (including platelets), serum electrolytes, creatinine,calcium, serum complement, random urine for total protein, creatinine, renal imaging studies.
Antedencenthx of streptococcal throat of skin infection- post-streptococcal GN
Ask about symptoms of swelling-facial, perioral,pedal edema, or ascites
Symptom of pulmonary edema/ CHF (egdyspnoea with exertion, orthopnoea, SOB)
Gross hematuria (eg dark, rust, coke, tea coloured)
Family hx, other family member with nephritis or renal failure- Alport syndrome
The general terms GN and nephritis are not specific enough to be very useful for treatment or prognosis!!!
Epistaxis, headache, encephalopathy- severe hypertension
Nonspecific symptoms eg malaise, fever, anorexia, weakness
For tubulointestinal nephritis- try to obtain a history of a known etiology (eg bacterial, viral, drug related, metabolic, other)
TIN, usually hx of polyuria than oliguria
FBC- anemia, leucocytosis
Urinalysis and culture- hematuria, proteinuria, RBCs cast,other cellular masts, pyuria?
Bacteriological an serology- Anti streptolysin-O titer (>200IU/mL), Anti-DNAse B, throat swab/skin swab, lupus serology, serum IgA
Measure complement level- C3
RFT- blood urea, serum creatinine, electrolytes, BUN
Acute poststreptococcal GGN- low C3, positive ASOT and anti DNAase B
TIN- hematuria, eosinophilia, sterile pyuria, low grade proteinuria, eosinophiluria, urinary WBc casts
Renal ultrasonography- usually to exclude other causes of hypertension and hematuria but usually not conducted in real cut nephritic sydrome
light microscopy: lymphocytes, PMN leukocytes
Immunofluoroscene- IgG, IgA, IgM, or complement
Electron- deposit in mesangial, subendothelial, or subepithelial
Low complement C3 levels- return to normal after 3-4 weeks
Treat the primary pathology- immunosuppressive med eg steroids or cyclophosphamide in lupus
Supportive care- Fluid and electrolyte balance, diuretics, Ca channel blocker, ACEi, monitor rapid deterioration in renal function
Diet- fluid restriction, sodium, potassium restriction, Ca supplement
Complication of severe hypertension (e.g. cerebral haemorrhage, seizure, enchepalopathy,stroke, end organ damage)
Complication of renal failure (e.g. hyperkalemia, fluid overload, electrolyte abnormality, uremic symtoms, anemia, abnormal bone mineralization, sexual dysfunction, poor growth, anorexia)
Complication of primary disease (eg SLE)