Childhood-onset Lupus Nephritis Initial Glucocorticoid-dose Harmonization Trial (LIGHT Trial) (LIGHT)

Low- Versus High-Dose Initial Glucocorticoid Therapy for Childhood-Onset Proliferative Lupus Nephritis: a Multicenter Open-Label Noninferiority Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis (LN); Childhood-onset Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: High-dose prednisone; Drug: Low-dose prednisone

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sihao Gao, MD, PhD; Phone Number: 86-10-69155727; Email: sihao.gao@gmail.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Contact: Sihao Gao, MD, PhD; Phone Number: 86-10-69155727; Email: sihao.gao@gmail.com
      • Principal Investigator: Hongmei Song, MD, PhD
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Children's hospital, Capital Medical University
      • Contact: Huawei Mao, MD, PhD; Phone Number: 86-10-59616318; Email: maohwei@qq.com
      • Principal Investigator: Huawei Mao, MD, PhD
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Not yet recruiting
      • Chidren's Hospital of Chongqing Medical University
      • Contact: Xuemei Tang, MD; Phone Number: 86-23-63630957; Email: tangxuemei2008@163.com
      • Principal Investigator: Xuemei Tang, MD
  • Guangdong
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • Shenzhen Children's Hospital
      • Contact: Jun Yang, MD; Phone Number: 86-75-58395620; Email: rogasansz@163.com
      • Principal Investigator: Jun Yang, MD
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • The Second Xiangya Hospital of Central South University
      • Contact: Xiaochuan Wu, MD; Phone Number: 86-731-85295259; Email: wuxiaochuan@sina.com
      • Principal Investigator: Xiaochuan Wu, MD
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Children's Hospital of Nanjing Medical University
      • Contact: Haiguo Yu, MD; Phone Number: 86-25-83117830; Email: yuhaiguo73@126.com
      • Principal Investigator: Haiguo Yu, MD
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • Jilin University
      • Contact: Sirui Yang, MD; Phone Number: 86-431-88783761; Email: sryang@jlu.edu.cn
      • Principal Investigator: Sirui Yang, MD
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Not yet recruiting
      • Children's Hospital of Fudan University
      • Principal Investigator: Li SUN, MD
      • Contact: Li Sun, MD; Phone Number: 86-21-64932829; Email: lillysun@263.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group (High-dose group); Standard high-dose glucocorticoid therapy	Drug: High-dose prednisone; All participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. In the standard-dose (control) group, oral prednisone will be initiated at 1.4-1.6 mg/kg/day (maximum 60 mg/day), followed by gradual tapering according to the predefined schedule. For participants weighing <40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.
Experimental: Intervention group (Low-dose group); Low-dose glucocorticoid therapy	Drug: Low-dose prednisone; All participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. Participants in the intervention group will receive oral prednisone at an initial dose of 0.6-0.8 mg/kg/day, with a maximum dose of 30 mg/day, followed by gradual tapering according to the predefined schedule. For participants weighing <40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. The estimated cumulative prednisone dose over 24 weeks will be approximately 50% of that in the control group. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Renal Response at Week 24	Total renal response (TRR) is defined as achievement of complete renal response (CRR), primary efficacy renal response (PERR), or partial renal response (PRR). Complete renal response (CRR) is defined as meeting both of the following criteria: Proteinuria <0.5 g/1.73 m², or 24-hour urinary protein excretion <300 mg/m², or urine protein-to-creatinine ratio (UPCR) <0.5 g/g; and; Estimated glomerular filtration rate (eGFR) within the normal range, or eGFR ≥85% of baseline, or a normal serum creatinine level with an increase of no more than 25% from baseline. Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: UPCR <0.7 g/g; and; eGFR ≥80% of baseline or eGFR ≥60 mL/min/1.73 m². Partial renal response (PRR) is defined as meeting both of the following criteria: A ≥50% reduction in proteinuria from baseline and UPCR <3 g/g; and; eGFR ≥85% of baseline.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Renal Response at Week 12 and 24	CRR is defined as meeting both of the following criteria: (1) Urine protein <0.5 g/1.73 m², or 24-hour urine protein <300 mg/m², or urine protein-to-creatinine ratio (UPCR) <0.5 g/g; AND (2) Estimated glomerular filtration rate (eGFR) within the normal range; or eGFR at least 85% of baseline; or normal serum creatinine with an increase of no more than 25% from baseline.	Week 12, 24
Primary Efficacy Renal Response at Week 12 and 24	PERR is defined as meeting both of the following criteria: (1) UPCR <0.7 g/g; AND (2) eGFR at least 80% of baseline or eGFR ≥60 mL/min/1.73 m².	Week 12, 24
Partial Renal Response at Week 12 and 24	PRR is defined as meeting both of the following criteria: (1) Urine protein reduced by ≥50% from baseline and UPCR <3 g/g; AND (2) eGFR at least 85% of baseline.	Week 12, 24
Time to TRR	Total renal response (TRR) is defined as achievement of complete renal response (CRR), primary efficacy renal response (PERR), or partial renal response (PRR). Complete renal response (CRR) is defined as meeting both of the following criteria: 1. Proteinuria <0.5 g/1.73 m², or 24-hour urinary protein excretion <300 mg/m², or urine protein-to-creatinine ratio (UPCR) <0.5 g/g; and 2. Estimated glomerular filtration rate (eGFR) within the normal range, or eGFR ≥85% of baseline, or a normal serum creatinine level with an increase of no more than 25% from baseline. Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: 1. UPCR <0.7 g/g; and 2. eGFR ≥80% of baseline or eGFR ≥60 mL/min/1.73 m². Partial renal response (PRR) is defined as meeting both of the following criteria: 1. A ≥50% reduction in proteinuria from baseline and UPCR <3 g/g; and 2. eGFR ≥85% of baseline.	Week 0-24
Time to CRR	Complete renal response (CRR) is defined as meeting both of the following criteria: (1) Urine protein <0.5 g/1.73 m², or 24-hour urine protein <300 mg/m², or urine protein-to-creatinine ratio (UPCR) <0.5 g/g; (2) Estimated glomerular filtration rate (eGFR) within the normal range; or eGFR at least 85% of baseline; or normal serum creatinine with an increase of no more than 25% from baseline.	Week 0-24
Time to PERR	Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: (1) UPCR <0.7 g/g; (2) eGFR at least 80% of baseline or eGFR ≥60 mL/min/1.73 m².	Week 0-24
Time to PRR	Partial renal response (PRR) is defined as meeting both of the following criteria: (1) Urine protein reduced by ≥50% from baseline and UPCR <3 g/g; (2) eGFR at least 85% of baseline.	Week 0-24
Change of C3 from baseline to Week 24	To assess the improvement of SLE serum activity	Week 0, 24
Changes of C4 from baseline to Week 24	To assess the improvement of SLE serum activity	Week 0, 24
Change of anti-dsDNA titer from baseline to Week 24	To assess the improvement of SLE disease activity	Week 0, 24
Change of anti-dsDNA value from baseline to Week 24	To assess the improvement of SLE disease activity	Week 0, 24
Change of SLEDAI-2K from baseline to Week 24	To assess the level of disease activity improvement by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.	Week 0, 24
Change of PGA from baseline to Week 24	Physician Global Assessment (PGA) is a clinical tool utilizing a 0 to 3 visual analogue scale to measure overall disease activity by experienced rheumatologists.	Week 0, 24
Change of ParentGA from baseline to Week 24	Parental Global Assessment (ParentGA) is a parent-reported outcome measure used to quantify a caregiver's perception of their child's overall disease impact and well-being. ParentGA consists of a horizontal line containing 21 circles numbered from 0 to 10. The scale moves in 0.5 increments. The score of 0 indicates "very well" (best possible health status/disease activity) and 10 indicates "very poor" (worst possible health status/disease activity).	Week 0, 24
Change of PedsQL from baseline to Week 24	The Pediatric Quality of Life Inventory (PedsQL) is a modular assessment tool used to measure health-related quality of life in children, evaluating physical, emotional, social, and school functioning to generate an overall health score.	Week 0, 24
Change of serum creatinine from baseline to Week 24	To measure renal function levels	Week 0, 24
Change of eGFR from baseline to Week 24	eGFR (estimated Glomerular Filtration Rate) is a calculated value used to assess kidney filtration function. Pediatric eGFR [mL/(min·1.73m2)] = K × 88.4 × Height (cm)/Serum Creatinine (μmol/L). When serum creatinine is measured using the Jaffe method, the K coefficient is proportional to an individual's muscle mass and varies with age. In adolescents, it varies according to sex: Children and adolescent females: K = 0.55; Adolescent males: K = 0.77. When creatinine is measured using an enzymatic assay: K = 0.413	Week 0, 24
Change of 24-hour urine protein from baseline to Week 24	A 24-hour urine protein test measures kidney function by quantifying how much protein the body excretes in a full day.	Week 0, 24
Changes of UPCR from baseline to Week 24	A UPCR (Urine Protein Creatinine Ratio) test measures the amount of protein relative to creatinine in a single urine sample. It is a highly accurate, convenient alternative to 24-hour urine test.	Week 0, 24
Rate of LN treatment failure at Week 24	LN treatment failure is defined as the occurrence of any of the following: Death;; New-onset end-stage renal disease (ESRD), or the need for dialysis or kidney transplantation;; Doubling of serum creatinine (compared with the baseline level);; Renal flare, defined by either (a) or (b):Proteinuric flare: after excluding secondary causes such as infection, 24-hour urinary protein excretion or the urine protein-to-creatinine ratio (UPCR) increased to at least twice the baseline level; orNephritic flare: after excluding secondary causes such as infection, serum creatinine increased by 25% from baseline, together with any of the following:24-hour urinary protein increased to at least twice the baseline level and exceeded 2 g/24 h, or the equivalent UPCR;New-onset hematuria graded as 2+ or more;New-onset cellular casts.	Week 24
Rate of renal flare at Week 24	Renal flare, defined by either (a) or (b): Proteinuric flare: after excluding secondary causes such as infection, 24-hour urinary protein excretion or the urine protein-to-creatinine ratio (UPCR) increased to at least twice the baseline level; or; Nephritic flare: after excluding secondary causes such as infection, serum creatinine increased by 25% from baseline, together with any of the following:24-hour urinary protein increased to at least twice the baseline level and exceeded 2 g/24 h, or the equivalent UPCR;New-onset hematuria graded as 2+ or more;New-onset cellular casts.	Week 24
Rate of SLE flare at Week 24	SLE flare is defined according to SELENA-SLEDAI definitions: An increase in the SLEDAI score of ≥3 points compared with the previous assessment;; New-onset or worsening manifestations of lupus activity, including cutaneous lesions, oral or nasal ulcers, pleuritis, pericarditis, arthritis, fever, neuropsychiatric lupus, vasculitis, nephritis, myositis, platelet count <60 × 10⁹/L, hemolytic anemia (hemoglobin <70 g/L or a decrease of >30 g/L), lupus myocarditis, or lupus pneumonitis;; Initiation or dose escalation of medications because of disease activity, including NSAIDs, glucocorticoids, cyclophosphamide, methotrexate, or azathioprine;; A Physician Global Assessment (PGA; range, 0-3) score of ≥1.	Week 24
Rate of LLDAS at Week 24	LLDAS was defined as meeting all of the following criteria: SLEDAI-2K score ≤4, with no activity in major organ systems (renal, neuropsychiatric, cardiopulmonary, vasculitic, or constitutional activity), no hemolytic anemia, and no gastrointestinal activity;; No new manifestations of SLE disease activity compared with baseline;; SELENA-SLEDAI Physician Global Assessment score (range, 0-3) ≤1;; Prednisone dose, or equivalent glucocorticoid dose, ≤7.5 mg/day.	Week 24
Rate of DORIS remission at Week 24	DORIS remission is defined as meeting all of the following criteria: Clinical SLEDAI score = 0;; Physician Global Assessment score (range, 0-3) <0.5, irrespective of serological activity;; Treatment with antimalarial agents was permitted, as was prednisone at a dose of ≤5 mg/day (or an equivalent glucocorticoid dose) and/or stable immunosuppressive therapy, including biologic agents.	Week 24
PRINTO/ACR cSLE response rate at Week 24	Response was defined as improvement of at least 50% from baseline in any two of the five core outcome measures, with no more than one of the remaining measures worsening by more than 30%. The five core outcome measures were Physician Global Assessment of overall disease activity (PGA), Parent Global Assessment of disease activity (ParentGA), proteinuria, the SLE Disease Activity Index 2000 (SLEDAI-2K), and the physical functioning domain of the Pediatric Quality of Life Inventory (PedsQL).	Week 24
Changes of Childhood Lupus Improvement Index (CHILI) from baseline to Week 24	The Childhood Lupus Improvement Index (CHILI) is a validated measure of treatment response in childhood-onset SLE that primarily captures clinically meaningful improvement. The score is calculated using five core outcome measures: Physician Global Assessment of overall disease activity (PGA), Parent Global Assessment of disease activity (ParentGA), proteinuria assessed by the urine protein-to-creatinine ratio (UPCR) or 24-hour urinary protein excretion, the SLE Disease Activity Index 2000 (SLEDAI-2K), and the physical functioning domain of the Pediatric Quality of Life Inventory (PedsQL). (PMID: 30680946)	Week 0, 24
Rate of clinical, minor, moderate and major improvement in cSLE at Week 24	Using the CHILI absolute-change definition, clinical improvement is defined as a CHILI score ≥54; minor improvement as CHILI ≥15; moderate improvement as CHILI ≥68; and major improvement as CHILI ≥92.	Week 0, 24
Scores and changes of pGTI from baseline to Week 12 and 24	The pediatric glucocorticoid toxicity index (pGTI) is a composite index including 10 glucocorticoid toxicity domains: body mass index, growth and development, glucose tolerance, lipid metabolism, systolic blood pressure, bone mineral density, glucocorticoid-induced myopathy, skin toxicity, neuropsychiatric effects, and infection. (PMID: 35917759)	Week 0, 12, 24
SLICC/ACR Damage Index at Week 24	The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR Damage Index, SDI) is designed to assess cumulative, irreversible organ damage occurring since the onset of SLE. It encompasses 39 types of chronic, irreversible damage across 12 organ systems, irrespective of ongoing inflammatory disease activity. (PMID: 8607884)	Week 24
Category, incidence and severity of adverse events	Adverse events should be assessed at each study visit, including the event name, timing, management, severity, and outcome. Adverse event grading: Grade 1 (mild): Asymptomatic or mild symptoms; clinical or diagnostic findings only; no treatment required. Grade 2 (moderate): Requires minor or local treatment and limits instrumental activities of daily living. Grade 3 (severe): Medically significant but not immediately life-threatening; hospitalization may be required; limits self-care activities of daily living. Grade 4 (life-threatening): Requires urgent intervention. Grade 5 (death): Death related to the adverse event.	Week 0-24
Change of blood pressure from baseline to Week 24	To measure improvement of kidney function, and monitor the side effect by glucocorticoids.	Week 0, 24
Change of fasting blood glucose from baseline to Week 24	To evaluate adverse events of glucocorticoids	Week 0, 24
Changes of serum triglycerides from baseline to Week 24	To monitor adverse effects of glucocorticoids	Week 0, 24
Changes of height from baseline to Week 24	To measure the growth velocity of children, and monitor the adverse events of glucocorticoids	Week 0, 24
Changes of bone marrow density from baseline to Week 24	To monitor the side effects of glucocorticoids, bone mineral density (BMD) is measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine.	Week 0, 24

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Children's Hospital of Fudan University; Beijing Children's Hospital; Second Xiangya Hospital of Central South University; Shenzhen Children's Hospital; Nanjing Children's Hospital; Children's Hospital of Chongqing Medical University; Jilin University
• Investigators: Principal Investigator: Hongmei Song, MD, PhD, Peking Union Medical College

Publications and helpful links

General Publications

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• Sammaritano LR, Askanase A, Bermas BL, Dall'Era M, Duarte-Garcia A, Hiraki LT, Rovin BH, Son MBF, Alvarado A, Aranow C, Barnado A, Broder A, Brunner HI, Chowdhary V, Contreras G, Felix C, Ferucci ED, Gibson KL, Hersh AO, Izmirly PM, Kalunian K, Kamen D, Rollins B, Smith BJ, Thomas A, Timlin H, Wallace DJ, Ward M, Azzam M, Bartels CM, Cunha JS, DeQuattro K, Fava A, Figueroa-Parra G, Garg S, Greco J, Cuellar-Gutierrez MC, Iyer P, Johannemann AS, Jorge A, Kasturi S, Kawtharany H, Khawandi J, Kirou KA, Legge A, Liang KV, Lockwood MM, Sanchez-Rodriguez A, Turgunbaev M, Williams JN, Turner AS, Mustafa RA. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis Rheumatol. 2025 Sep;77(9):1115-1135. doi: 10.1002/art.43212. Epub 2025 May 7.
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Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: July 13, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Children; Therapy; Systemic lupus erythematosus; Lupus nephritis; Glucocorticoid
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone
• Other Study ID Numbers: K10405; 2025-PUMCH-C-047 (Other Grant/Funding Number: National High Level Hospital Clinical Research Funding)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For privacy concerns, individual participant data will not be shared. Summary data will be available with publication and upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No