Kidney Week

Abstract: FR-PO1168

Association of Plasma Uromodulin with Kidney Outcomes in the SPRINT Trial

Session Information

• CKD: Kidney Function and Extrarenal Complications
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Ikeme, Jesse C., University of California San Francisco, San Francisco, California, United States

Jesse C. Ikeme, MD

• Scherzer, Rebecca, University of California San Francisco, San Francisco, California, United States

Rebecca Scherzer, PhD

• Garimella, Pranav S., University of California San Diego, La Jolla, California, United States

Pranav S. Garimella, MD, MPH, FASN

• Hallan, Stein I., Norges Teknisk-Naturvitenskapelige Universitet, Trondheim, Norway

Stein I. Hallan, MD, PhD

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz, PhD

• Estrella, Michelle M., University of California San Francisco, San Francisco, California, United States

Michelle M. Estrella, MD

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Shlipak, Michael, University of California San Francisco, San Francisco, California, United States

Michael Shlipak, MD, MPH

Background

Uromodulin (UMOD) is a kidney tubule biomarker that may help identify persons at greater risk of eGFR decline. We evaluated the associations of plasma UMOD with kidney outcomes in persons with CKD and hypertension.

Methods

This was a secondary analysis of the Systolic Blood Pressure Intervention Trial, in which an intensive SBP target reduced risk of CV events and mortality. Plasma UMOD was measured at baseline in 2,302 participants with eGFR <60 ml/min/1.73m². Acute kidney injury (AKI) was determined based on serious adverse event reporting during the trial. Quarterly labs were used to determine 30% and annual % eGFR decline from baseline. Cox proportional hazards (AKI, 30% eGFR decline and ESKD) and linear mixed models (annual % eGFR decline) were adjusted for baseline characteristics, including eGFR and albuminuria.

Results

Plasma UMOD and eGFR had a Spearman correlation of 0.47. In fully adjusted models, each standard deviation higher plasma UMOD was associated with lower risk of 30% eGFR decline and slower annual eGFR decline (Table). There were no independent associations with risk of future AKI or ESKD. The association with lower risk of 30% eGFR decline appeared stronger in those randomized to a usual SBP target (HR 0.73, 95% CI 0.62-0.87) than in those randomized to an intensive SBP target (HR 0.90, 0.79-1.02; p-interaction = 0.03). Associations with other outcomes appeared similar across randomized treatment arms (p-interaction >0.10).

Conclusion

Higher plasma UMOD levels are independently associated with lower risk of 30% eGFR decline and slower decline in eGFR among hypertensive persons with nondiabetic CKD.

Adjusted associations of baseline plasma uromodulin (per SD higher) with kidney outcomes in 2,302 SPRINT participants with CKD

Models adjusted for randomized SBP target, age, sex and race; baseline eGFR, log urine albumin, log urine creatinine, smoking, BMI, SBP, anti-hypertensive medications number and class, cardiovascular disease, heart failure, high-density lipoprotein, total cholesterol, and statin use.

Funding

• NIDDK Support