the efficacy and safety of dapagliflozin in the treatment of hereditary kidney disease with proteinuria in children

Conditions: Pediatric Hereditary Kidney Diseases

Summary: 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

chronic kidney disease (ckd) poses a significant public health threat to children, with hereditary kidney diseases exhibiting limited therapeutic efficacy in reducing proteinuria. global studies have demonstrated that dapagliflozin significantly reduces proteinuria in adults with ckd; however, its role in pediatric hereditary kidney diseases lacks strong evidence .this study aims to investigate the efficacy and safety of dapagliflozin in children with proteinuric hereditary kidney diseases. this is a multicenter, open-label, block-randomized, crossover clinical trial with 1:1 allocation. a total of 44 participants will be enrolled to compare the efficacy and safety of dapagliflozin combined with standard renin-angiotensin-aldosterone system inhibitor (raasi) therapy versus raasi therapy alone. the primary endpoint is the change in 24-hour urinary protein levels from baseline to 12 weeks of treatment. secondary endpoints include: urinary protein-to-creatinine ratio (upcr), urinary albumin-to-creatinine ratio (uacr), serum albumin levels, estimated glomerular filtration rate (egfr), blood pressure changes, and body weight changes.

Eligibility criteria:
inclusion criteria: * 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. * willingness to sign the informed consent form. exclusion criteria:exclusion applies if any of the following criteria are met: * 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. * evidence of urinary tract obstruction such as dysuria. * blood pressure below the 5th percentile for the same gender, age, and height. * organ transplantation. * tumor. * presence of any of the following definite evidence of liver disease: alt/ast reaching 2 times the normal value, hepatic encephalopathy, esophageal varices, or portal shunt surgery. * comorbid medical conditions that may affect drug absorption, distribution, metabolism, and excretion, including but not limited to any of the following: active inflammatory bowel disease within the past 6 months, history of major gastrointestinal surgery (such as gastrectomy, gastroenterostomy, intestinal resection), gastrointestinal ulcer, gastrointestinal or rectal bleeding within the past 6 months, pancreatic injury or pancreatitis within the past 6 months. * subjects at risk of dehydration or volume depletion, which may affect drug efficacy or safety. * participation in other drug trials within the previous 4 weeks. * blood loss exceeding 400 ml within the previous 8 weeks. * poor past medication compliance or unwillingness to complete the trial. * any other medical conditions that may place the patient at a higher risk due to participation in this study.

Keywords: hereditary kidney diseases proteinuria dapagliflozin children