REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)

Inclusion Criteria:

1. Provide informed consent ± assent

2. Participant age 1-18 years

3. Diagnosis of idiopathic nephrotic syndrome (defined as nephrotic-range proteinuria [first morning or 24-hour urine protein/creatinine ratio ≥200mg/mmol or ≥3+ proteinon dipstick] and either hypoalbuminemia [serum albumin <30g/L] or edema)

4. Active nephrotic syndrome relapse at time of enrolment (defined as recurrence ofnephrotic-range proteinuria [≥3+ protein on dipstick for ≥3 consecutive days18 ORfirst morning or 24-hour urine protein/creatinine ratio ≥200mg/mmol AND ≥1+ proteinon dipstick for ≥3 consecutive days])

5. Ability to take oral medication and willingness to adhere to either study prednisoneregimen

6. Ability and willingness to adhere to home urine and symptom monitoring during theinitial two-week period after assigned treatment initiation

7. Have not been previously included in the RESPONSE trial

8. Participant located in Ontario, Canada at the time of study enrolment

Exclusion Criteria:

1. Prednisone treatment (at any dose) for the active relapse episode for >2-daysprior to study enrolment

2. Relapse episode within the past 6-weeks (i.e., date of relapse onset within 6-weeksprior to date of enrolment)

3. Current receipt of high-dose maintenance prednisone therapy (dose >0.6mg/kg onalternate days or >0.3mg/kg daily)

4. Steroid-resistant nephrotic syndrome classification (defined as lack of completeremission within 6-weeks after initiating daily steroid treatment at a standard dosefor the initial episode of nephrotic syndrome)

5. Congenital or monogenic cause of nephrotic syndrome (defined as age at diagnosis <1-year or known/suspected monogenic cause of nephrotic syndrome)

6. Secondary cause of nephrotic syndrome (includes membranous nephropathy,post-infectious glomerulonephritis [GN], complement-mediated GN [e.g., C3glomerulopathy and immune complex-GN], IgA nephropathy, IgA vasculitis, lupusnephritis, medication-induced nephrotic syndrome, malignancy-induced nephroticsyndrome, active hepatitis B or C infection, or active HIV infection)

7. Presence of moderate-to-severe peripheral edema (grade 3+; indentation depth ≥5mmand rebound time >15 seconds)

8. Hospitalization since the onset of the active relapse episode

9. Acute kidney injury (KDIGO stage ≥1) since the onset of the active relapse episode

10. Active or prior known or suspected venous thromboembolism during a relapse episode

11. Active pregnancy or lactation

12. Any condition or diagnosis, that could in the opinion of the Principal Investigatoror delegate interfere with the participant's ability to comply with studyinstructions, might confound the interpretation of the study results, or put theparticipant at risk