Steroid Sensitive
Nephrotic Syndrome
Ref: Indian Pediatrics May 2021
Nephrotic syndrome
• edema
• heavy proteinuria (>1 g/m2 daily; >40 mg/m2/hr)
• hypoalbuminemia (serum albumin<3 g/dL)
the most common kidney diseases in childhood
Annual incidence ranging from 1.2 to 16.9 per 100,000 children
Mostly idiopathic. 5-10% have underlying systemic illness
Kidney biopsy reveals: MCD(80%) , FSGS and MPGN in 7-8% each.
Therapy with prednisolone results in complete remission of proteinuria in 85-90% (SSNS).
50% show frequent relapses or steroid dependence, and 3-10% show late steroid resistance
Guideline 1: Evaluation
Essential at onset
• Urinalysis
• Complete blood counts
• Blood urea, creatinine,
electrolytes,
• total protein, albumin,
• Total cholesterol
• Tuberculin test
Additional evaluation, at onset or relapse
• Chest radiography: Positive tuberculin test or history of
contact; suspected lower respiratory tract infection
• Renal ultrasonography: Planned for kidney biopsy;
presence of gross hematuria; suspected renal vein
thrombosis
• Complete blood counts: Suspected systemic infection
• Blood urea, creatinine, albumin, electrolytes: Severe
edema, hypovolemia/dehydration; oliguria/anuria;
prolonged (>72 h)diuretic therapy
• Complement C3, C4, antinuclear antibody, ASO :Gross,
persistent microscopic hematuria; sustained
hypertension; suspected secondary cause (systemic
lupus, IgA vasculitis, C3glomerulopathy)
• Serum transaminases; hepatitis B surface antigen;
antibody against hepatitis C virus: History of jaundice
or liver disease
• Periodic monitoring, if relapsing illness
Guideline 2: Kidney biopsy
• persistent microscopic hematuria, gross hematuria, or acute kidney injury not attributed to
hypovolemia
• systemic features: fever, rash, arthralgia, low complement C3
• initial or late corticosteroid resistance
• prior to initiating therapy with CNI
• prolonged (>30-36 months) therapy with CNI, or reduced kidney function during their use.
light microscopy and immunofluorescence examination
Electron microscopy study
Guideline 3: Therapy for the first episode of nephrotic syndrome
therapy for the initial episode
• prednisolone at a dose of 60 mg/m2/day (2 mg/kg/day, max 60 mg in 1-2 divided doses) for 6
weeks,
• followed by 40 mg/m2 (1.5 mg/kg, max 40 mg as single morning dose) on alternate days for the
next 6 weeks, and
• then discontinued
Guideline 4: Therapy of relapses
relapses treated with
• prednisolone at 60 mg/m2/day (2 mg/kg/day; max 60 mg) in single or divided-
doses until remission,
• followed by 40 mg/m2 (1.5 mg/kg, max 40 mg) on alternate days for 4-weeks.
• Usually with daily dose regimen relapse occurs in 1-2wks, if not extended upto 6wks
• Lack of remission after 6wks of daily dose regimen indicates late steroid resistance
Guideline 5: Management of frequent relapses and steroid dependence
Frequent relapses
2 or more relapses in
the first 6-mo
≥3relapses in any 6mo
≥4 relapses in one yr
Steroid dependence
2 consecutive
relapses when on AD
steroids, or
within 14 days of its
discontinuation
5.2 Long-term corticosteroids
• In frequent relapses, taper prednisolone to reach a minimum dosage of 0.5-0.7
mg/kg on alternate days and continued for 6-12 months.
• In patients receiving long term alternate-day prednisolone, administer the same
dose daily for 5-7 days during fever or respiratory tract infection
5.3 Non-corticosteroid therapies
• steroid-sparing agent used
i.
failed therapy with alternate-day prednisolone
ii. steroid toxicity Hyperglycemia; obesity; short stature; raised IOP; cataract; myopathy; osteonecrosis; psychosis)
iii. complicated relapses
(i) hypovolemia (ii) severe infection (iii) thrombosis)
• patients failing AD prednisolone, use either levamisole or MMF for 12-24 months.
• Use MMF or cyclophosphamide in patients with significant steroid toxicity, high
steroid threshold, complicated relapses, of failure of therapy with levamisole
Cyclophosphamide
• Leucopenia <4000, therapy withheld
• Oral 2-2.5mg/kg/day for 8-12 wks
• IV 500mg/m2 monthly for 6 doses
• Mesna regime 60-160% of cuclophosphamide dose
• 20% dose give 3 occasions( before, along with and 4hrs later to CyP)
• Cummulative dose <168mg/kg due to risk of gonadal toxicity
Cyclosporine trough level 80-120ng/ml
Tacrolimus trough level 5-8ng/ml
5.4 Difficult-to-treat steroid sensitive nephrotic syndrome
• CNI (cyclosporine or tacrolimus) recommended
• either failed CNI or prolonged therapy with CNI, use rituximab
• Rituximab should be administered
i.
during disease remission (not in relapse, because it will be excreted in urine)
ii. after ruling out acute and chronic infections
iii. causes B cell depletion.(B cell recovery takes 6-9 months)
Guideline 6: Management of Hypovolemia and Edema
• Edema, a cardinal feature of nephrotic syndrome
• classified based on appearance and percentage weight gain from baseline
I.
mild (≤7% increase)
II.
moderate (8-15%)
III. severe (>15% increase)
• 6.1 Hypovolemia
patients with moderate to severe edema to be assessed for intravascular volume status before initiating
therapy with diuretics
Guideline 7: Infections and Immunization
7.2 Immunization
GUIDELINE 8: TRANSITION OF CARE
• SSNS is a self limiting disease.
• Majority of patients outgrow the illness by puberty.
• patients who continue to have relapses beyond adolescence (>
18years of age) be transitioned into care by adult nephrologist.
Thank you