This study is a multicenter, randomized controlled crossover trial aimed to evaluate the efficacy and safety of dapagliflozin in the treatment of hereditary kidney disease with proteinuria in children
Confirmed diagnosis of hereditary kidney disease (identification of pathogenic genes through molecular genetic testing; for Alport syndrome, molecular diagnosis is not necessarily required if diagnosed based on clinical and pathological findings; for those with a clear family history and a high clinical suspicion of hereditary kidney disease).
24 - hour urinary protein level > 0.2 g or urinary protein to creatinine ratio (UPCR) > 0.2 mg/mg.
Calculate the estimated glomerular filtration rate (eGFR) using the Schwartz formula (36.5 * height in cm / serum creatinine in μmol/L), with eGFR ≥ 60 ml/min/1.73 m².
Stable use of the basic treatment drug RAASi (including ACEI/ARB) for more than 4 weeks, and no dosage adjustment during the treatment period.
Treatment with hormones/immunosuppressive agents within the previous 4 weeks.
Treatment with SGLT2 inhibitors within the previous 4 weeks.
Comorbid diabetes.
Uncontrolled urinary tract infection.
Crossover
Dapagliflozin+Standard Treatment for 12 weeks,washout period for 4 weeks，then Standard Treatment alone for12 weeks
Drug①Dapagliflozin+Standard Treatment for 12 weeks. Dapagliflozin therapy (Farxiga®, 10 mg tablets) is administered orally once daily,with dose adjustment based on body weight: 5 mg/day for participants ≤30 kg; 5 mg/day initially (first week), then increased to 10 mg/day for participants \>30 kg Standard Treatment:standard renin-angiotensin-aldosterone system inhibitor (RAASi) therapy(The dosage will be maintained at the pre-enrollment level throughout the entire treatment period, with no adjustments made during therapy.),This combined therapy will be administered for 12 weeks. ② Washout period for 4 weeks Participants should maintenance RAASi therapy while discontinuing dapagliflozin. ③Standard Treatment alone for an additional 12 weeks. To ensure compliance, all participants are required to complete a daily medication log.If any adverse events (AEs) occur, appropriate clinical interventions will be promptly implemented
Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks
Drug①Standard Treatment for 12 weeks Standard Treatment:Standard renin-angiotensin-aldosterone system inhibitor (RAASi) therapy alone for 12 weeks.(The dosage will be maintained at the pre-enrollment level throughout the entire treatment period, with no adjustments made during therapy.) ②Washout period for 4 weeks Participants should maintenance RAASi therapy while discontinuing dapagliflozin. ③Dapagliflozin+Standard Treatment for 12 weeks Dapagliflozin therapy (Farxiga®, 10 mg tablets) is administered orally once daily,with dose adjustment based on body weight: 5 mg/day for participants ≤30 kg; 5 mg/day initially (first week), then increased to 10 mg/day for participants \>30 kg.This combined therapy will be administered for 12 weeks To ensure compliance, all participants are required to complete a daily medication log.If any adverse events (AEs) occur, appropriate clinical interventions will be promptly implemented
Changes in 24-hour urinary protein excretion from baseline to week 12
The change in 24-hour urinary protein excretion from baseline to week 12 of treatment with dapagliflozin combined with RAASi . According to the research protocol, the 24-hour urine of the pediatric patients is collected during the planned follow-up period, and the pyrogallol red method is used for the quantitative test of the protein in the urine.
Changes in urinary protein to creatinine ratio (UPCR) levels from baseline to week 12
The change in the urinary protein to creatinine ratio (UPCR) levels from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The pyrogallol red method is used for detecting urinary protein, and the enzymatic method is used for detecting urinary creatinine. UPCR = urinary protein/urinary creatinine (mg/mg).
Changes in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12
The change in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The immunoturbidimetric method is used for detecting urinary albumin, and the enzymatic method is used for detecting urinary creatinine. UACR = urinary albumin/urinary creatinine (mg/g).
Changes in serum albumin levels from baseline to week 12
The change in the serum albumin level from baseline to week 12 of treatment with dapagliflozin combined with RAASi. Venous blood is collected, and the test is conducted through the routine biochemical examination in the hospital.
Changes in estimated glomerular filtration rate from baseline to week 12
The change in the estimated glomerular filtration rate (eGFR) from baseline to week 12 of treatment with dapagliflozin combined with RAASi. Venous blood is collected, and the serum creatinine level is detected through the routine biochemical examination in the hospital. The eGFR is calculated according to the Schwartz formula (36.5 \* height in cm / serum creatinine in μmol/L).
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Children's Hospital of Fudan University
Lead sponsor
Guangzhou Women and Children's Medical Center
Collaborator
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Collaborator
Shandong Provincial Hospital
Collaborator
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Collaborator
Wuhan Children's Hospital
Collaborator
Xuzhou Children Hospital
Collaborator
First Affiliated Hospital, Sun Yat-Sen University
Collaborator
Kunming Children's Hospital
Collaborator
The Children's Hospital of Zhejiang University School of Medicine
Collaborator
Children's Hospital of Nanjing Medical University
Collaborator
Zhengzhou Children's Hospital, China
Collaborator
Xiamen Women's and Children's Hospital
Collaborator
Guiyang Maternity and Child Health Care Hospital
Collaborator
Maternal and Child Health Care Hospital of Hainan Province
Collaborator
Children's Hospital of The Capital Institute of Pediatrics
Collaborator
Second Affiliated Hospital of Wenzhou Medical University
Collaborator
Xian Children's Hospital
Collaborator
The Second Hospital of Hebei Medical University
Collaborator
Wuxi Women's & Children's Hospital
Collaborator
First People's Hospital of Urumqi
Collaborator
