UMOD-ulating CKD risk: untangling the relationship between urinary uromodulin, blood pressure, and kidney disease

A new Mendelian randomization study finds evidence that genetically predicted higher levels of urinary uromodulin are associated with lower kidney function and higher blood pressure. Bidirectional and multivariable Mendelian randomization suggests the association with higher blood pressure appears to be partially through decreased kidney function, but blood pressure does not appear to mediate the association of uromodulin with low kidney function. We describe the methods used for the bidirectional and multivariable Mendelian randomization analyses and examine the validity of the assumptions and implications of the results. Copyright (C) 2021, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Automated summary

A new Mendelian randomized study discovered that genetically predicted higher levels of urinary uromodulin are linked to lower kidney function and higher blood pressure. Bidirectional and multivariable Mendelian randomization analysis suggested that the association with higher blood pressure may be partially through decreased kidney function, without blood pressure mediating the association of uromodulin with low kidney function.