Identifying Early Urinary Biomarkers of Kidney Damage in Type 1 Diabetes

Identifying Early Urinary Biomarkers of Kidney Damage in Type 1 Diabetes 150 150 Mary Bates, PhD

Markers of renal tubule injury and oxidative stress indicate diabetic nephropathy before microalbuminuria.

Diabetic nephropathy is a common complication of type 1 diabetes. Traditionally, measurement of microalbuminuria is used to screen children with diabetes for diabetic nephropathy. However, evidence suggests that damage to the kidneys may begin soon after diagnosis, much earlier than microalbuminuria can be detected. Microalbuminuria usually correlates with the development of the renal injury and thus the interest to detect early signs of injury before permanent damage has occurred.

In a new study, researchers from Nationwide Children’s investigated urinary biomarkers of kidney damage and oxidative stress that may signal the early stages of diabetic nephropathy in pediatric diabetes patients. In addition, the researchers explored how these biomarkers are associated with blood pressure patterns and glycemic variability.

The researchers enrolled participants between 10 and 21 years old with type 1 diabetes and performed continuous glucose monitoring and ambulatory blood pressure monitoring on each participant. They analyzed participants’ urine samples for urinary neutrophil gelatinase-associated lipocalin (uNGAL), a marker of renal tubule health, and pentosidine, a marker of oxidative stress in the kidneys.

“We found that while the traditional marker of diabetic nephropathy, microalbuminuria, was negative in all but one of our patients, levels of uNGAL and pentosidine were significantly elevated in type 1 diabetes patients compared to controls. “This highlights the potential role of early urinary biomarkers of kidney damage before the development of microalbuminuria; ,” says Leena Mamilly, MD, an endocrinologist at Nationwide Children’s and the leading author of the study.

Dr. Leena Mamilly

Dr. Leena Mamilly

The study also showed a high prevalence of abnormal blood pressure dipping in patients with type 1 diabetes. Abnormal blood pressure patterns are known to be a predictor for complications in individuals with diabetes, and this study suggests they may be present before the development of microalbuminuria.

Lastly, the results raise the question of whether glycemic variability, rather than mean blood glucose (HbA1c), has a stronger impact on the development of diabetic nephropathy. The researchers say larger studies may be able to better capture the role of glycemic variability.

According to Nationwide Children’s nephrologist Mahmoud Kallash, MD, another of the study’s authors, the key finding is that diabetes begins to affect the kidneys soon after diagnosis and  early detection of kidney damage can lead to early intervention and prevention of further kidney disease.

Dr. Mahmoud Kallash

Dr. Mahmoud Kallash

“We found that uNGAL and pentosidine can be early markers of renal injury and maybe used to detect early renal injury before irreversible damage to the kidneys occurs,” he says. “We plan to use these data to build a long-term prospective study to confirm these findings and investigate whether treating patients early might prevent or slow the progression of their kidney disease.”



Mamilly L, Mastrandrea LD, Mosquera Vasquez C, Klamer B, Kallash M, Aldughiem A. Evidence of early diabetic nephropathy in pediatric type 1 diabetes. Frontiers in Endocrinology. 2021 Apr 28; 12:669954. Doi: 10.3389/fendo.2021.669954.


Image credit: Nationwide Children’s


About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.