Kidney-DISCOVER

carDIovaScular and renal outCOmes in patients with type 2 diabetes recoVERed from AKI (DISCOVER)

Background

Acute kidney injury (AKI) is caused by a loss of kidney function. This leaves the body unable to remove waste products, and balance water and electrolyte levels effectively. When kidneys are damaged, albumin, a protein found in the blood, can pass into the urine. This is called albuminuria and is a sign of kidney disease.

Some people with AKI may experience it short-term and recover their kidney function. For others, AKI may progress further and develop into chronic kidney disease (CKD), especially for those who have other co-existing conditions that require treatment.

AKI is common among people with type 2 diabetes mellitus (T2DM). T2DM is the most common type of diabetes, and people with T2DM have an increased risk of developing complications that can damage the heart (cardiovascular) and brain (cerebrovascular) as well as the kidneys.

A new class of oral anti-hyperglycaemic drugs, called sodium glucose co-transporter 2 (SGLT2) inhibitors, can be used in the treatment of T2DM. They work by increasing the removal of glucose, and in turn lowering blood glucose levels.

There is now a growing amount of research evidence to show SGLT2 inhibitors have additional benefits in people who are at risk of cardiovascular and kidney disease. SGLT2 inhibitors have been shown to reduce the progression of kidney disease and death from kidney and cardiovascular causes. These SGLT2 inhibitors therefore show a protective effect in people whose kidney function is impaired.

Currently there is no evidence whether SGLT2 inhibitors provide a continued kidney-protective effect in people with T2DM who have recovered from AKI.

Aim

To assess the feasibility of this trial and measure any changes in albuminuria. The trial will be considered feasible if the total number of participants are recruited, they remain in the trial and on the allocated treatment for the 12-week duration and complete the follow up schedule. Changes in albuminuria will be measured by the urinary albumin-creatinine ratio.

Research Methodology

This is a pilot, multicentre, feasibility, double-blind, parallel group, phase III, randomised control trial. Initially two Australian kidney services will be involved, with plans to expand as required. Participants aged 18 years or older who have T2DM with albuminuria and have recently recovered from AKI (within the last 30 days) will provide consent. Consented participants will be randomised to receive either 10mg dapagliflozin (an SGLT2 inhibitor) or a matched control (one capsule daily) for 12 weeks. Participants will be followed up at various time points (6, 12 and 16 weeks) and have data collected from medical records, and blood and urine sample analysis.

Current Status

Human Research Ethics Committee approval for kidney services to be involved in the trial is being obtained, with the aim to start recruitment in at least one kidney service by the end of April 2023.

The project is in partnership with the Concord Repatriation General Hospital and Prince of Wales Hospital.