Novel Study to Test Three in One MRI to Detect Diabetic Kidney Disease in Kids and Teens

Research at UH Rainbow funded by prestigious Hartwell Foundation grant

Innovations in Pediatrics | Fall 2022

A team at UH Rainbow Babies & Children’s Hospital is launching a new study testing whether a brief but complex multimodal MRI can be used as an improved screening test for diabetic kidney disease (DKD) in children and teens. This pioneering approach has not be studied before outside University Hospitals.

Katherine Kutney, MD

Why it matters: As many as 30 percent of children and teens with type 2 diabetes will develop DKD, with the number rising over time, and the condition is more aggressive in the pediatric population. However, current urine and blood tests used to detect the condition are often inaccurate and fail to predict which patients will progress rapidly to end-stage renal failure. At the same time, the number of children and teens with obesity and type 2 diabetes continues to climb, increasing the number at risk of developing DKD.

The New Study

Led by UH Rainbow pediatric endocrinologist Katherine Kutney, MD, with a prestigious grant from the Harwell Foundation, the research team here will use MRI to gather data in three different ways, showing the structure, function, blood flow and metabolism of patients’ kidneys.

More Precise Targeting of Care

The hope is that by separating kids and teens who are developing DKD from those who are not, the new potent drugs used to treat type 2 diabetes can limited to those children who are at most risk for progressive DKD.

“Fortunately, the new diabetes medications, SGLT-2 inhibitors, may help slow the progression of DKD,” Dr. Kutney says. “Despite their renal-protective effects, however, the inhibitors carry a risk of necrotizing genitourinary infections and life-threatening diabetic-induced ketoacidosis, so it is critical they be used only in the subset of children who are at most at risk for progressive DKD.”

Study Methods

The new study at UH Rainbow will employ three MRI measures, enabled by state-of-the-art magnetic resonance fingerprinting – a quantitative MR technology developed at University Hospitals and Case Western Reserve University in 2011.

“Evaluating three promising renal MRI measures rather than choosing a single technique increases the likelihood of capturing the relevant physiologic features of DKD,” Dr. Kutney says.

The three modes

• Arterial spin labeling (ASL) to measure renal blood flow
• Blood oxygen labeled dependent (BOLD) to measure tissue hypoxemia
• Diffusion tensor imaging (DTI) to measure structural changes

The 20- to 30-minute scan will generate data from all three modes simultaneously and will not use intravenous contrast media, making it more patient-friendly.

Study Population

Dr. Kutney and her team will first complete baseline MRI scans in 45 patients between the ages of 12 and 19 -- 15 type 2 diabetes patients with early signs of DKD, 15 type 2 diabetes patients with no early signs of DKD and 15 healthy controls. These scans will allow the team to determine whether there are MRI cutoff values that indicate DKD – which are currently lacking.

“There are currently no data on relevant MRI thresholds for kidney disease in youth with type 2 diabetes, which my research aims to provide,” Dr. Kutney says.

Next, Dr. Kutney and her team will follow 10 patients identified with DKD and 10 patients identified with no DKD for an additional two years, getting two additional yearly multimodal MRI scans. This data will help the team determine whether the innovative approach can detect DKD progression over time.

A Unique Approach with Promising Advantages

Multimodel MRI techniques to measure kidney perfusion, oxygenation and structure have never been evaluated together, Dr. Kutney says, and none of these techniques have been described in youth-onset type 2 diabetes

“Prior studies have investigated a single technique in adults with chronic kidney disease, but there is no published literature on detecting and staging early disease in children when intervention could make the greatest difference,” she says.

However, she says the new approach has the potential to be a superior screen for DKD compared with current urine albumin tests and calculations of glomerular filtration rate.

“Urine albumin tests provide poor sensitivity and specificity for DKD and fail to identify patients at risk for rapid progression to renal failure,” she says. “Urine albumin screening is also limited by false positive tests, which occur with exercise, illness, cold, seizures, menstruation, and postural proteinuria. Glomerular filtration rate is a much more specific indicator of DKD, but is insensitive to early disease, falling only after kidney damage has significantly progressed. Matching screening tests to known pathologic features of CKD is a more logical strategy to detect early disease. Fortunately, key physiologic changes of DKD can be quantified non-invasively with advanced magnetic resonance imaging techniques.”

Clear Potential for Benefit

Dr. Kutney says that a more sensitive, reliable biomarker of DKD in children and teens will allow pediatric endocrinologists like herself to better target SGLT-2 inhibitors to their type 2 diabetes patients who are most likely to benefit, preventing unnecessary harm from these drugs from coming to children at low risk.

“These drugs have very serious side effects,” she says. “Given these risks, it is incumbent upon the medical community to ensure that only the patients who are most likely to benefit from SGLT-2 inhibitors will be treated with them.”

For those who are prescribed SGLT-2 inhibitors, the multimodal MRI will also likely be able to show their effects on specific pathophysiologic features of DKD.

Beyond this, Dr. Kutney says, there’s also a psychological benefit. A more accurate screen for DKD will also help young type 2 diabetes patients who experience anxiety, depression and uncertainty about their future.

“Because there's such a strong genetic component to it, many of our kids who present with youth-onset type 2 diabetes have had a family member who has had an amputation, has needed kidney dialysis or maybe has passed away from complications,” she says. “They internalize that a lot and many patients come to think of that as inevitable. It is an uphill battle to convince these kids that this future is not predefined for them. I think that anything that we can do to help them see the potential for a bright and healthy future would be very psychologically helpful and might even inspire them to feel like they have more control over their disease. With a better screening tool, children at lower risk for rapidly progressive DKD could be spared unnecessary anxiety, and children at higher risk could receive renal protective therapies, with the goal of preventing progression to chronic kidney disease and renal transplant at a young age. It is now more important than ever to have sensitive and specific tools to diagnose and monitor DKD in youth.”

For more information about this study, please email Peds.Innovations@UHhospitals.org.

Contributing Expert:
Katherine Kutney, MD
Pediatric Endocrinologist
UH Rainbow Babies & Children’s Hospital
Assistant Professor of Pediatrics
Case Western Reserve University School of Medicine