Uromodulin and risk for kidney failure

While uromodulin (UMOD) is the most abundant protein found in urine, it is also released at much lower levels into the circulation. As serum levels appear to decline with kidney failure, uromodulin is a promising biomarker of tubule health. 

Investigators used stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK) to evaluate whether serum UMOD levels were associated with kidney failure with replacement therapy (KFRT) and mortality risk. 

Among 500 participants with chronic kidney disease attributed to hypertension (mean age 54 years; 37% female; mean GFR 45 mL/min/1.73 m²) and for whom stored serum samples were available from visits at 0, 12 and 24 months, there were 161 KFRT events over a median 8.5 years. 

After adjustment for baseline sociodemographic and clinical factors, kidney measures and randomised treatment groups, a 50% lower baseline UMOD level was associated with a significantly higher risk of developing KFRT (adjusted HR, 1.35; 95% CI, 1.07–1.70).

In analyses of the association of UMOD slope with KFRT, there were 129 events over a median 7.0 years. Those with the steepest UMOD decline were more likely to develop KFRT. For annual UMOD change, each 1 standard deviation lower change was associated with a 67% higher risk.

There were 86 deaths over a median 7.9 years. Neither baseline UMOD nor UMOD change were associated with mortality.

There was a steeper decline in UMOD levels in those randomised to an intensive blood pressure goal compared to those aiming for a standard goal (P=0.002), and in those receiving metoprolol compared to ramipril (P<0.001).

Overall, the results suggest that in African–American adults with CKD and hypertension, lower levels of UMOD lead to worse kidney outcomes. The authors conclude that studies are needed to better understand the mechanisms behind this association.

The full article can be read here.