Dapagliflozin for children with hereditary kidney disease and proteinuria

The Efficacy and Safety of Dapagliflozin in the Treatment of Hereditary Kidney Disease With Proteinuria in Children: a Prospective, Randomized Crossover Trial

This trial will test whether adding dapagliflozin to standard ACE inhibitor or ARB therapy reduces protein in the urine of children with hereditary kidney disease.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 6 Years to 18 Years
• Sex: All
• Sponsor: Children's Hospital of Fudan University (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06890143 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label, block-randomized crossover Phase 3 trial will enroll 44 children with hereditary kidney disease and proteinuria. Participants are randomized 1:1 to receive dapagliflozin plus stable RAAS inhibitor therapy for 12 weeks followed by a 4-week washout and 12 weeks of RAASi alone, or the reverse sequence. The primary outcome is change in 24-hour urinary protein from baseline to 12 weeks, with secondary outcomes including UPCR, UACR, serum albumin, eGFR, blood pressure, and body weight. Safety and tolerability will be monitored throughout the treatment periods.

Who should consider this trial

Good fit: Children with a confirmed hereditary kidney disease, measurable proteinuria (24-hour >0.2 g or UPCR >0.2 mg/mg), eGFR ≥60 ml/min/1.73 m², and stable RAAS inhibitor therapy are the intended participants.

Not a fit: Children with low eGFR (<60 ml/min/1.73 m²), no measurable proteinuria, recent use of immunosuppression, or unstable RAASi dosing are unlikely to benefit or be eligible for this protocol.

Why it matters

Potential benefit: If successful, adding dapagliflozin could lower proteinuria in affected children and potentially slow progression of kidney damage.

How similar studies have performed: Large adult trials have shown dapagliflozin reduces proteinuria and slows CKD progression, but its effectiveness in children with hereditary kidney diseases remains largely untested.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Children's Hospital of Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Yihui Zhai

Conditions Pediatric Hereditary Kidney Diseases; hereditary kidney diseases; proteinuria; dapagliflozin; children