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High serum uromodulin levels suggest lower risk for coronary artery calcification in type 1 diabetes

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December 6, 2018

Coronary artery calcification and diabetic kidney disease appear to develop more slowly in the presence of higher serum uromodulin concentrations in adults with type 1 diabetes, according to findings published in Diabetes Care.

Petter Bjornstad

“We need biomarkers to help us better understand which patients with type 1 diabetes will develop coronary artery disease and diabetic kidney disease, the leading causes of mortality in type 1 diabetes,” Petter Bjornstad, MD, assistant professor of pediatrics and medicine department of pediatrics, section of endocrinology department of medicine, division of renal diseases and hypertension at the University of Colorado School of Medicine, told Endocrine Today. “Earlier risk stratification translates to earlier risk management and potentially better outcomes.”

Using data from the Coronary Artery Calcification in Type 1 Diabetes study, Bjornstad and colleagues assessed values for albumin to creatinine ratio, estimated glomerular filtration rate, serum uromodulin and coronary artery calcification in 247 of 527 participants with type 1 diabetes (53% women; mean age, 39.6 years; median diabetes duration, 24.8 years). Measurements were taken at baseline and at a mean follow-up time of 12.1 years.

Participants who had higher levels of serum uromodulin at baseline had less risk for coronary artery calcification progression (OR = 0.68; 95% CI, 0.48-0.97), although when adjusting for duration of diabetes, this finding only approached significance. The decrease in risk for coronary artery calcification progression related to increased levels of serum uromodulin was significant 4 years after baseline before (OR = 0.67; 95% CI, 0.52-0.87) and after (OR = 0.67; 95% CI, 0.52-0.88) adjusting for type 1 diabetes duration. Lower odds for chronic kidney disease (OR = 0.44; 95% CI, 0.24-0.83), elevated albumin excretion (OR = 0.37; 95% CI, 0.16-0.86) and rapid GFR decline (OR = 0.56; 95% CI, 0.35-0.91) were also linked to higher concentrations of serum uromodulin.

When comparing the participants with coronary artery calcification progression (n = 121; mean age 45 years; mean HbA1c, 7.7%) vs. those without (n = 126; mean age, 35 years; mean HbA1c, 7.6%), participants with progression had longer diabetes duration (mean, 30 years vs. 22 years; P < .0001), higher systolic blood pressure (115 mm Hg vs. 108 mm Hg; P < .0001), lower eGFRs (93 mL/min/1.73 m2 vs. 107 mL/min/1.73 m2; P < .0001) and lower serum uromodulin levels (138 ng/mL vs. 159.5 ng/mL; P = .02).

“Serum uromodulin is inexpensive and readily available for research and has the potential to be implemented in clinical practice to determine the risk of patients with type 1 diabetes developing coronary artery disease and diabetic kidney disease,” Bjornstad said. “Future research should combine serum uromodulin with other promising biomarkers to further improve risk prediction. Additionally, data are needed to understand how changes in serum uromodulin concentrations correlate with existing and novel therapies.” – by Phil Neuffer

Disclosures: The study was supported by funding from the National Heart, Lung, and Blood Institute. Bjornstad reports that he received consultant fees, speaking honorarium or both from Horizon Pharma, Boehringer Ingelheim, Bayer and Bristol-Myers Squibb, and is on a scientific advisory board for Xortx. Please see the study for all other authors’ relevant financial disclosures.