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

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.

Timeline

Start

2026-04-23

Primary completion

2027-05-30

Completion

2027-10-30

Publications

• Background Agarwal R, Green JB, Heerspink HJL, Mann JFE, McGill JB, Mottl AK, Rosenstock J, Rossing P, Vaduganathan M, Brinker M, Edfors R, Li N, Scheerer MF, Scott C, Nangaku M; CONFIDENCE Investigators. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. N Engl J Med. 2025 Aug 7;393(6):533-543. doi: 10.1056/NEJMoa2410659. Epub 2025 Jun 5.
• Background Kanbay M, Copur S, Bakir CN, Covic A, Ortiz A, Tuttle KR. Glomerular hyperfiltration as a therapeutic target for CKD. Nephrol Dial Transplant. 2024 Jul 31;39(8):1228-1238. doi: 10.1093/ndt/gfae027.
• Background Staplin N, Roddick AJ, Neuen BL, Anker SD, Bhatt DL, Butler J, Cherney DZ, Docherty KF, Fletcher RA, Inzucchi SE, Jardine M, Mahaffey KW, McGuire DK, McMurray JJV, Neal B, Packer M, Patel SM, Perkovic V, Sabatine MS, Solomon S, Vaduganathan M, Wanner C, Wheeler DC, Zannad F, Haynes R, Heerspink HJL, Herrington WG; SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C). Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. 2026 Jan 20;335(3):220-232. doi: 10.1001/jama.2025.20835.
• Background Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
• Background The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.
• Background Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. No abstract available.
• Background Ortiz A, Arreola Guerra JM, Chan JCN, Jha V, Kramer H, Nicholas SB, Pavkov ME, Wanner C, Wong LP, Cheung M, King JM, Grams ME, Jadoul M, Tuttle KR; Conference Participants. Preventing chronic kidney disease and maintaining kidney health: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2025 Oct;108(4):555-571. doi: 10.1016/j.kint.2025.04.005. Epub 2025 Jun 19.
• Background Alcalde-Ortiz ML, Jaramillo-Arriaga F, Ibarra-Orenday D, Gonzalez-Dominguez SI, Calzada-Gallegos HD, Pinales-Jimenez AA, Carrillo-Aguilera IA, Flota-Marin DA, Collazo-Zamores MG, Aguirre-Moreno PD, Gutierrez-Hernandez SD, Del Toro-Delgado V, Delgadillo-Castaneda R, Sanchez-Ortiz MDR, Sanchez-Gonzalez I, Ramos-Medellin CL, Chew-Wong A, Macias-Diaz DM, Arreola-Guerra JM. Pediatric kidney dimensions and risk of persistent albuminuria in Mexican adolescents. Kidney Int. 2024 Apr;105(4):824-834. doi: 10.1016/j.kint.2023.11.034. Epub 2024 Jan 25.
• Background Macias Diaz DM, Corrales Aguirre MDC, Reza Escalera AL, Tiscareno Gutierrez MT, Ovalle Robles I, Macias Guzman MJ, Garcia Diaz AL, Gutierrez Pena MC, Alvarado-Najera AN, Gonzalez Dominguez I, Villavicencio-Bautista JC, Herrera Rodriguez AA, Marin-Garcia R, Avelar Gonzalez FJ, Wong AC, Galvan Guerra E, Delgadillo Castaneda R, Prado Aguilar CA, Zuniga-Macias LP, Arreola Guerra JM. 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 Jan 14;15(7):1300-1311. doi: 10.1093/ckj/sfac018. eCollection 2022 Jul.
• 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 Garcia-Garcia G, Gutierrez-Padilla A, Perez-Gomez HR, Chavez-Iniguez JS, Morraz-Mejia EF, Amador-Jimenez MJ, Romero-Munoz AC, Gonzalez-De la Pena MDM, Klarenbach S, Tonelli M. Chronic kidney disease of unknown cause in Mexico: The case of Poncitlan, Jalisco. Clin Nephrol. 2020 Supplement-Jan;93(1):42-48. doi: 10.5414/CNP92S107.
• Background Gutierrez-Pena M, Zuniga-Macias L, Marin-Garcia R, Ovalle-Robles I, Garcia-Diaz AL, Macias-Guzman MJ, Delgado-Bentites A, Macias-Diaz DM, Prado-Aguilar CA, Vega de la Rosa A, Delgadillo-Castaneda R, Chew-Won A, Reyes-Acevedo R, Reyes-Campos DM, Martinez-Guevara MA, Mendoza-Enciso EA, Nava-Becerra B, Piza-Jimenez MA, Arreola Guerra JM. 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 Jan 15;14(4):1197-1206. doi: 10.1093/ckj/sfaa229. eCollection 2021 Apr.
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