ORLANDO – Low serum uromodulin proved to be an independent predictor of all-cause mortality in a prospective study of 529 patients with stable coronary artery disease followed for up to 8 years, according to Christoph Saely, MD, vice president of the Vorarlberg Institute for Vascular Investigation and Treatment in Feldkirch, Austria.
“Baseline serum uromodulin is a valuable biomarker to predict overall mortality in coronary patients independent from kidney disease and the presence of type 2 diabetes. The lower the serum uromodulin, the higher the mortality,” he noted in an interview at the annual meeting of the American College of Cardiology.
Uromodulin is a protein produced only by the kidneys. It’s important for water and electrolyte balance and also has anti-inflammatory properties. Although uromodulin is present in both urine and blood, urinary uromodulin levels fluctuate widely and have proved unreliable as a marker for adverse patient outcomes. Serum levels are another matter entirely.In addition to presenting new evidence at ACC 2018 of serum uromodulin’s merits as a predictor of increased mortality risk in patients with CAD, Dr. Saely and his coinvestigators also showed that low serum uromodulin is associated with chronic kidney disease, type 2 diabetes, and prediabetes. Moreover, those with normal glucose metabolism and kidney function but a low serum uromodulin at baseline were at increased risk of developing abnormal glucose metabolism and impaired renal function during 4 years of follow-up.
Of the 529 patients with stable CAD, 95 died during follow-up. Among those with a low baseline serum uromodulin, defined bimodally as a level below 123.3 ng/mL, the mortality rate was 27.6%, roughly twice the 13.7% figure in patients with a baseline uromodulin above that threshold.
In a multivariate analysis adjusted extensively for age, sex, smoking, LDL cholesterol, HDL cholesterol, C-reactive protein, diabetes, estimated glomerular filtration rate, and N-terminal pro b-type natriuretic peptide level, a high baseline serum uromodulin was independently associated with a 43% reduction in the risk of mortality, according to Dr. Saely, who is both a cardiologist and an endocrinologist.
The overall mortality rate was 41% in patients with diabetes and a low baseline uromodulin, 20% in those with low uromodulin but not diabetes, 18% in diabetic patients with high uromodulin, and less than 13% with high uromodulin and no diabetes.
Enzyme-linked immunosorbent assay tests for uromodulin are marketed in Europe but remain investigational for now in the United States.
Dr. Saely reported having no financial conflicts of interest; the study was conducted without commercial support.
SOURCE: Saely C. ACC 2018, Abstract 1212-418/418.