Kidney Week

Abstract: FR-PO756

In SPRINT Participants With Creatinine Elevations During Follow-Up, Trajectories of Tubule Injury Markers Associate With eGFR Decline

Session Information

• Hypertension and CVD: Clinical, Outcomes, Trials
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1501 Hypertension and CVD: Epidemiology‚ Risk Factors‚ and Prevention

Authors

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

Joachim H. Ix,

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

Ronit Katz,

• Shigenaga, Judy, University of California San Francisco, San Francisco, California, United States

Judy Shigenaga,

• Cheung, Alfred K., University of Utah Health, Salt Lake City, Utah, United States

Alfred K. Cheung,

• Raphael, Kalani L., Oregon Health & Science University, Portland, Oregon, United States

Kalani L. Raphael,

• Hallan, Stein I., St. Olav University Medical Center, Trondheim, Norway

Stein I. Hallan,

• Seegmiller, Jesse C., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Jesse C. Seegmiller,

• Malhotra, Rakesh, University of California San Diego, La Jolla, California, United States

Rakesh Malhotra,

• Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States

Vasantha Jotwani,

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

Pranav S. Garimella,

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

Michael Shlipak,

Background

Elevations in serum creatinine (SCr) often prompt clinicians to halt therapies. We hypothesized that biomarkers of tubule cell damage could prognosticate eGFR trajectories in this setting.

Methods

The SPRINT trial randomized 9361 hypertensive patients to an intensive (<120mmHg) vs. standard (<140mmHg) systolic blood pressure target. Of these, 652 (7.0%) had SCr elevations (ΔSCr ≥ 0.3 mg/dL from baseline) during follow-up. We measured four urine biomarkers indexed to urine Cr (IL-18, KIM-1, MCP-1 & YKL-40) & 1 plasma (UMOD) biomarker at baseline and annual visits concurrent with SCr elevations. Intra-individual changes were calculated; those in the highest quartile were considered “abnormal”. The outcome was ΔeGFR from SCr elevation through the end of follow-up. Models adjusted for clinical risk factors and stratified by randomization.

Results

The median ΔSCr was 0.42 (IQR 0.34, 0.56) mg/dL. At baseline, mean age was 70 years, 33% were female, mean eGFR was 62±25 ml/min/1.73m², & 72% were randomized to the intensive arm. Over 23.5 months mean follow-up after SCr elevation, mean (SD) ΔeGFR was 1.46 ± 2.60% annually. In the standard arm, longitudinal increases of urine IL-18 and KIM-1 or decreases in plasma UMOD associated with faster declines in eGFR, independent of clinical risk factors and albuminuria. In the intensive arm, only increasing uMCP-1 associated with subsequent eGFR trajectory, and the direction was toward eGFR improvement.

Conclusion

Among hypertensive patients with SCr elevations, worsening kidney tubule damage associates with faster subsequent eGFR decline. These relationships were not observed in the intensive arm, where SCr elevations more likely result from hemodynamic causes.

Funding

• NIDDK Support