The Efficacy and Safety of Sodium-glucose Cotransporter 2 Inhibitors in Patients With Acute Kidney Disease (ESS-AKD)

Acute kidney disease (AKD) happens between 7 and 90 days after an initial kidney injury (AKI). This period is crucial because it can determine whether the condition worsens into chronic kidney disease (CKD). Despite knowing this, there is no proven treatment to improve outcomes for people with AKD.

Recent studies have shown that drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors can slow down the worsening of chronic kidney disease, help with heart failure, and reduce the risk of death. Now, researchers are looking into whether these drugs can also help prevent acute kidney injury (AKI) and improve outcomes for AKD patients.

Our project will explore the use of SGLT2 inhibitors in patients with AKD, with the belief that these drugs can safely reduce the amount of protein (albumin) in the urine and improve kidney health. To address this, investigators plan to conduct a large, multicenter study in Taiwan. This study will be randomized and placebo-controlled, meaning some patients will receive the SGLT2 inhibitors while others will receive a placebo (a harmless, inactive substance). Investigators will include AKD patients with and without diabetes, focusing on reducing the protein in their urine and monitoring for any serious side effects.

The goal of this trial is to provide strong evidence on whether SGLT2 inhibitors can be an effective treatment for AKD. If successful, this could offer a new strategy to prevent the progression from AKI to CKD and improve the health and outcomes of patients with kidney disease.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: dapagliflozin; Drug: empagliflozin; Drug: canagliflozin; Other: Other anti-diabetic drug or no anti-diabetic drug

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Szu-Yu Pan, MD, PhD; Phone Number: 41845 +886-23123456; Email: szuyupan@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Szu-Yu Pan; Email: szuyupan@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years and < 80 years
• Diagnosed with acute kidney disease
• Estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73m²
• Albuminuria > 100 mg/g or proteinuria > 300 mg/g (adjusted by urine creatinine)
• Diagnosed with diabetes or chronic kidney disease

Exclusion Criteria:

• Received sodium-glucose cotransporter 2 (SGLT2) inhibitors within 28 days prior to enrollment
• Patients with type 1 diabetes
• Receiving aggressive immunosuppressive therapy for glomerulonephritis
• Obstructive nephropathy
• Polycystic kidney disease
• Malignancy within 3 months or expected to undergo aggressive treatment such as chemotherapy, radiation therapy, immunotherapy, or targeted therapy in the future
• Pregnant or breastfeeding women
• Clinically assessed as not having recovered from acute kidney injury
• Clinically assessed as at high risk for complications related to SGLT2 inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Other: Other anti-diabetic drug or no anti-diabetic drug; Other anti-diabetic drug or no anti-diabetic drug for 90 days during the acute kidney disease period. Other anti-diabetic drug includes metformin, sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitor, insulin, α-glucosidase inhibitors, thiazolidinediones, and glucagon-like peptide-1 receptor agonist.
Experimental: SGLT2i	Drug: dapagliflozin; Sodium-glucose cotransporter 2 inhibitor for 90 days during the acute kidney disease period.; Drug: empagliflozin; Sodium-glucose cotransporter 2 inhibitor for 90 days during the acute kidney disease period.; Drug: canagliflozin; Sodium-glucose cotransporter 2 inhibitor for 90 days during the acute kidney disease period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albuminuria	The changes in albuminuria compared with baseline	Day 28 and Day 90
Discontinuation of SGLT2i	Development of adverse events leading to discontinuation of SGLT2i	Day 0 to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR	The changes in eGFR	Day 28 to Day 84 or Day 28 to Day 168
Major adverse kidney events	eGFR reduction >50%, dialysis, or death	Day 0 to Day 180
Major adverse cardiovascular events	hospitalization due to heart failure or death	Day 0 to Day 180
Death	All-cause mortality	Day 0 to Day 180
Amputation	Any amputation event	Day 0 to Day 180

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: China Medical University Hospital; Chang Gung Memorial Hospital; National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 25, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 28, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: albuminuria; acute kidney disease; sodium-glucose cotransporter 2 inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Renal Insufficiency; Proteinuria; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Kidney Injury; Albuminuria; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates; Glucosides; Glycosides; Thiophenes; Canagliflozin; empagliflozin; dapagliflozin
• Other Study ID Numbers: 202404095MINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No