Uromodulin shows promise for risk stratification, prediction of kidney disease and atherosclerosis
SAN DIEGO — In a new study, serum uromodulin levels were strongly associated with risk for incident diabetic kidney disease and coronary atherosclerosis in adults with type 1 diabetes.
“Uromodulin may hold promise to help risk stratification and predict development of diabetic kidney disease and coronary artery disease,” Petter Bjornstad, MD, pediatric endocrinology fellow at Children’s Hospital Colorado/Barbara Davis Center for Diabetes, said during a presentation here.
Bjornstad and colleagues examined the relationship between serum uromodulin and the development of albuminuria (urinary albumin-to-creatinine ratio 30 mg/g), chronic kidney disease (CKD; estimated glomerular filtration rate < 60 mL/min/1.73 m2) and coronary artery calcium (CAC; change in square root transformed CAC volume 2.5; assessed by 128-slide spiral computed tomography) over 12 years in the Coronary Artery Calcification in Type 1 Diabetes study. Serum uromodulin was measured using immunoassay kits from Meso Scale Discovery.
“There is a need for novel biomarkers to predict risk for diabetic kidney disease and coronary artery disease while disease is still clinically silent,” Bjornstad said.
He noted that uromodulin — also known as Tamm-Horsfall protein — is “the most abundantly found protein in the human urine.” Uromodulin is known for its antimicrobial properties, and recent research has demonstrated anti-inflammatory properties and an association with CKD risk, he said.
“The relationship between uromodulin and diabetic kidney disease and coronary artery disease in type 1 diabetes remains unclear,” he said.
In total, the study included 539 adults with type 1 diabetes. At baseline, the mean age was 40 years, mean HbA1c was 7.7% and mean diabetes duration was 25 years.
Overall, CAC progression was observed in 49% of adults with type 2 diabetes, incident CKD in 10.4%, decrease in eGFR in 7% and elevated albumin excretion in 6%, Bjornstad said here. When the researchers stratified their analysis by CAC progression, those who had CAC progression tended to be older and had lower uromodulin concentrations, lower eGFR at baseline, higher systolic blood pressure and longer duration of type 1 diabetes.
Serum uromodulin at baseline was associated with CAC progression (OR = 0.66; 95% CI, 0.47-0.94), incident albuminuria (OR = 0.27; 95% CI, 0.11-0.65) and incident CKD (OR = 0.39; 95% CI, 0.2-0.76) in adjusted models.
Every 1-SD increase in uromodulin at baseline conferred lower odds for incident CKD, incident elevated albuminuria, rapid eGFR decline and CAC progression in adjusted models, Bjornstad said.
In addition, when uromodulin was added to baseline models that included traditional risk factors, such as age and sex, plus the American Diabetes Association’s ABC goals (A1c, blood pressure, cholesterol), Bjornstad said it improved relative Integrated Discrimination Improvement (IDI) and correctly reclassified 27% of cases of CAC progression and 24% of cases of CKD.
The researchers are currently measuring uromodulin levels at follow-up visits to examine longitudinal changes. Bjornstad and colleagues are also working with the Diabetes Longevity Study group in Canada to validate these findings in a separate cohort. – by Katie Kalvaitis
Bjornstad P, et al. 1-OR. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.
Disclosures: Bjornstad reports receiving research support from the NIH.