Overview
Childhood-onset systemic lupus erythematosus (cSLE) is a severe chronic autoimmune disease with a high burden of major-organ involvement. Lupus nephritis (LN) affects more than half of children with SLE, and proliferative LN-including class III, IV, III+V, and IV+V disease-is associated with acute kidney injury, progression to end-stage kidney disease, and poor long-term outcomes.
Glucocorticoids remain a cornerstone of induction therapy for proliferative LN. However, the optimal initial dose in children is uncertain. Although recent adult SLE and LN guidelines increasingly recommend lower-dose glucocorticoid regimens with rapid tapering, pediatric guidelines still commonly recommend high initial prednisone doses of 1.5-2.0 mg/kg/day. Adult trials and comparative observational studies suggest that lower-dose glucocorticoid regimens may preserve efficacy while reducing treatment-related toxicity.
Because cumulative glucocorticoid exposure in children may impair growth, development, psychosocial well-being, and medication adherence, this trial will compare low-dose versus high-dose initial glucocorticoid regimens for induction treatment of pediatric proliferative LN. The objective is to determine whether a lower-dose regimen is non-inferior in efficacy while reducing glucocorticoid-related adverse effects and improving quality of life.
Eligibility
Inclusion Criteria:
- Age ≥6 years and \<18 years, with body weight ≥20 kg
- Meets the 2019 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus (SLE)
- Renal biopsy confirming Lupus Nephritis class III, IV, III+V, or IV+V according to the International Society of Nephrology / Renal Pathology Society (ISN/RPS) classification
- At screening: 24-hour urinary protein ≥1.0 g (or ≥25 mg/kg), or urine protein-to-creatinine ratio (UPCR) ≥1.0 g/g
- White blood cell count ≥3.0 × 10⁹/L and lymphocyte count ≥1.0 × 10⁹/L
- No prior intravenous methylprednisolone pulse therapy before enrollment, and glucocorticoid exposure ≤2 weeks before enrollment, with a maximum prednisone-equivalent dose ≤30 mg/day (or ≤1 mg/kg/day)
- Written informed consent obtained and good treatment compliance expected
Exclusion Criteria:
- Uncertain diagnosis of SLE, genetically confirmed monogenic lupus, or a history of immunodeficiency
- Severe infection, including hepatitis C, active hepatitis B, HIV infection, tuberculosis infection, severe fungal infection, etc.
- Severe neuropsychiatric lupus
- Peripheral blood hemoglobin \<60 g/L, platelet count \<10 × 10⁹/L, or concomitant aplastic anemia
- Severe cardiac insufficiency (NYHA functional class ≥ II)
- Severe pulmonary involvement, including pulmonary hemorrhage, respiratory failure, pulmonary embolism, or other conditions requiring respiratory support
- Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m²
- Severe gastrointestinal bleeding, pancreatitis, or hepatic lesions
- Patients deemed by the investigator to be unsuitable for participation in this trial
