Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Adolescents With Early Stages of Chronic Kidney Disease

NCT07405216 | Recruiting Phase 4 DMC

• 1 other identifier: INAER2026-1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic kidney disease (CKD) is highly prevalent in the state of Aguascalientes, Mexico, particularly among adolescents and young adults. Epidemiologic and histologic studies suggest that this burden is largely driven by reduced nephron endowment of prenatal origin, leading to compensatory glomerular hyperfiltration, adaptive podocytopathy, and persistent albuminuria at early stages of disease. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated nephroprotective effects in adult populations with CKD, including reductions in albuminuria and slowing of disease progression, independent of diabetes status. However, no randomized controlled trials have evaluated the efficacy and safety of SGLT2 inhibitors in adolescents with early-stage CKD and persistent albuminuria. This randomized, double-blind, placebo-controlled clinical trial aims to evaluate whether treatment with an SGLT2 inhibitor reduces albuminuria in adolescents aged 14 to 18 years with persistent microalbuminuria (albumin-to-creatinine ratio 30-300 mg/g) and preserved kidney function. Participants will be randomized in a 2:1 ratio to receive dapagliflozin 10 mg daily or placebo for six months. The primary outcome is the change in urinary albumin-to-creatinine ratio from baseline to six months. Secondary outcomes include changes in estimated glomerular filtration rate and safety outcomes.

Conditions

Albuminuria; Adolescent; Chronic Kidney Disease (Mild to Moderate); Sodium Glucose Co-Transporter 2 Inhibitors

Keywords

Chronic kidney disease; Persistent albuminuria; sodium glucose co-transporter 2 inhibitors

Outcome Measures

Primary Outcomes (1)

• Albuminuria

  The urinary albumin-to-creatinine ratio (ACR) will be calculated. The primary endpoint will be the log-transformed difference between baseline and six-month ACR. Absolute and relative (% reduction) changes in ACR will also be reported.

  2, 4 and 6 months

Secondary Outcomes (1)

• Glomerular filtration rate

  2,4 and 6 months

Other Outcomes (1)

• Incidence of treatment-related side effects (ortostatic hypotension, genital mycosis, urinary tract infection)

  2,4 and 6 months

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Adolescents with persistent albuminuria

Drug: Dapagliflozin (10mg Tab)

Placebo

PLACEBO COMPARATOR

Placebo 10 mg daily

Drug: Placebo

Interventions

Dapagliflozin (10mg Tab) DRUG

Dapagliflozin 10 mg daily

Dapagliflozin

Placebo DRUG

Placebo 10 mg daily

Placebo

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Residence in Aguascalientes
• Persistent albuminuria (ACR \>30 and \<300 mg/g)
• Estimated glomerular filtration rate ≥60 mL/min/1.73 m²
• No identifiable secondary cause (e.g., lupus, diabetes mellitus)
• Renal biopsy showing adaptive podocytopathy or perihilar focal segmental glomerulosclerosis -

You may not qualify if:

• Hypoalbuminemia
• Nephrotic syndrome
• Persistent macroalbuminuria (ACR \>300 mg/g)
• Secondary causes of CKD, including congenital anomalies of the kidney and urinary tract or polycystic kidney disease -

Sponsors & Collaborators

• Centenario Hospital Miguel Hidalgo: lead

Study Sites (1)

Instituto de atención Integral de Enfermedades Renales del Estado de Aguascalientes

Aguascalientes, Aguascalientes, 20000, Mexico

RECRUITING

Related Publications (20)

• 20. Agarwal R, Green JB, Heerspink HJL, et al. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. N Engl J Med. 2025;393(6):533-543. doi:10.1056/NEJMoa2410659

  BACKGROUND

• 19. Kanbay M, Copur S, Bakir CN, Covic A, Ortiz A, Tuttle KR. Glomerular hyperfiltration as a therapeutic target for CKD. Nephrol Dial Transplant. 2024;39(8):1228-1238. doi:10.1093/ndt/gfae027

  BACKGROUND

• 18. Staplin N, Roddick AJ, Neuen BL, et al. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. Published online November 7, 2025. doi:10.1001/jama.2025.20835

  BACKGROUND

• 17. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816

  BACKGROUND

• 16. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233

  BACKGROUND

• 15. KDIGO CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018

  BACKGROUND

• 14. Ortiz A, Arreola Guerra JM, Chan JCN, et al. Preventing chronic kidney disease and maintaining kidney health: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2025;108(4):555-571. doi:10.1016/j.kint.2025.04.005

  BACKGROUND

• 13. Alcalde-Ortiz ML, Jaramillo-Arriaga F, Ibarra-Orenday D, et al. Pediatric kidney dimensions and risk of persistent albuminuria in Mexican adolescents. Kidney Int. 2024;105(4):824-834. doi:10.1016/j.kint.2023.11.034

  BACKGROUND

• 12. Macias Diaz DM, Corrales Aguirre MDC, Reza Escalera AL, et al. Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin. Clin Kidney J. 2022;15(7):1300-1311. Published 2022 Jan 14. doi:10.1093/ckj/sfac018

  BACKGROUND

• 11. United States Renal Data System. 2024 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2024.

  BACKGROUND

• 10. Registro Estatal Únicio de Enfermedad Renal Crónica del Estado de Aguascalientes. Instituto de Servicios de Salud del Estado de Aguascalientes. https://www.issea.gob.mx/ercpub/en/RepPrevalenciaErcPbiPubV2.asp Date: January 11, 2026

  BACKGROUND

• 9. Garcia-Garcia G, Gutiérrez-Padilla A, Perez-Gomez HR, et al. Chronic kidney disease of unknown cause in Mexico: The case of Poncitlan, Jalisco. Clin Nephrol. 2020;93(1):42-48. doi:10.5414/CNP92S107

  BACKGROUND

• 8. Gutierrez-Peña M, Zuñiga-Macias L, Marin-Garcia R, et al. High prevalence of end-stage renal disease of unknown origin in Aguascalientes Mexico: role of the registry of chronic kidney disease and renal biopsy in its approach and future directions. Clin Kidney J. 2021;14(4):1197-1206. doi:10.1093/ckj/sfaa229

  BACKGROUND

• 7. Barquera S, Hernández-Barrera L, Trejo-Valdivia B, Shamah T, Campos-Nonato I, Rivera-Dommarco J. Obesidad en México, prevalencia y tendencias en adultos. Ensanut 2018-19 [Obesity in Mexico, prevalence andtrends in adults. Ensanut 2018-19.]. Salud Publica Mex. 2020;62(6):682-692. doi:10.21149/11630

  BACKGROUND

• 6. Arreola-Guerra JM, Martinez-Martinez JI, Multifactorial chronic kidney disease, Nephrology Dialysis Transplantation, 2025;, gfaf122, https://doi.org/10.1093/ndt/gfaf122

  BACKGROUND

• 5. GBD 2023 Chronic Kidney Disease Collaborators. Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025;406(10518):2461-2482. doi:10.1016/S0140-6736(25)01853-7

  BACKGROUND

• 4. Francis A, Harhay MN, Ong ACM, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. 2024;20(7):473-485. doi:10.1038/s41581-024-00820-6

  BACKGROUND

• 3. Institute for Health Metrics and Evaluation. Global Burden of Disease 2019. Accessed February 14, 2023. https://vizhub.healthdata.org/gbdcompare/

  BACKGROUND

• 2. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 Lancet. 2016;388(10053):1459-1544. doi:10.1016/S0140-6736(16)31012-1

  BACKGROUND

• 1. GBD 2023 Chronic Kidney Disease Collaborators. Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025;406(10518):2461-2482. doi:10.1016/S0140-6736(25)01853-7

  BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Albuminuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms

Central Study Contacts

Jose Manuel Arreola Guerra, PhD, MD

CONTACT

+524494632049; dr.jmag@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 12, 2026
• Study Start: April 23, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)