Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle's loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI> 25) and its relationship to stroke in patients.
Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions.
Results: The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p< 0.0001 and r²= 0.343, p= 0.0416 and r²= 0.102) respectively. Systemic uromodulin expression increased with BMI> 25 (p= 0.014). Presence of hypertension decreased uromodulin’s expression systemically (p= 0.018) and intracranially (p= 0.007).
Conclusions: Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.
The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998 and UK Center for Clinical and Translational Science (CCTS).
Armstrong, Gabriella-Salome K.; Frank, Jacqueline A.; McLouth, Christopher J.; Stowe, Ann M.; Roberts, Jill M.; Trout, Amanda L.; Fraser, Justin F.; and Pennypacker, Keith R., "Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression during Ischemic Stroke" (2021). Neurology Faculty Publications. 81.