Kidney Week

Abstract: TH-PO076

Urine Proteomic Signatures of Kidney Function Decline after Hospitalization

Session Information

• AKI: Clinical, Outcomes, and Trials - Epidemiology and Pathophysiology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Wen, Yumeng, Genentech Inc, South San Francisco, California, United States

Yumeng Wen, MD, PhD

• Menez, Steven, Johns Hopkins Medicine, Baltimore, Maryland, United States

Steven Menez, MD

• Thiessen Philbrook, Heather, Johns Hopkins Medicine, Baltimore, Maryland, United States

Heather Thiessen Philbrook

• Moledina, Dennis G., Yale University School of Medicine, New Haven, Connecticut, United States

Dennis G. Moledina, MD, PhD, FASN

• Bhatraju, Pavan K., University of Washington School of Medicine, Seattle, Washington, United States

Pavan K. Bhatraju, MD, MS

• Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Steven G. Coca, DO, MS

• Chinchilli, Vernon M., Penn State College of Medicine, Hershey, Pennsylvania, United States

Vernon M. Chinchilli, PhD

• Go, Alan S., Kaiser Permanente, Oakland, California, United States

Alan S. Go, MD

• Siew, Edward D., Vanderbilt University School of Medicine, Nashville, Tennessee, United States

Edward D. Siew, MD, MS, MSc

• Kimmel, Paul L., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Paul L. Kimmel, MD, FASN

• Ikizler, Talat Alp, Vanderbilt University School of Medicine, Nashville, Tennessee, United States

Talat Alp Ikizler, MD, FASN

• Hsu, Chi-yuan, University of California San Francisco School of Medicine, San Francisco, California, United States

Chi-yuan Hsu, MD, MS, MSc, FASN

• Himmelfarb, Jonathan, University of Washington School of Medicine, Seattle, Washington, United States

Jonathan Himmelfarb, MD, FASN

• Cantley, Lloyd G., Yale University School of Medicine, New Haven, Connecticut, United States

Lloyd G. Cantley, MD, FASN

• Parikh, Chirag R., Johns Hopkins Medicine, Baltimore, Maryland, United States

Chirag R. Parikh, MD, PhD, FASN

Group or Team Name

• Kidney Precision Medicine Project (KPMP).

Background

Urine proteomics may identify proteins specifically excreted by the kidney that provide mechanistic insights into future adverse kidney outcomes.

Methods

In 174 patients (48% with acute kidney injury [AKI]) from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI) cohort, we used Olink to profile 2783 urine proteins in samples from 3 months after index hospitalization. We used linear mixed-effects models to identify proteins associated with estimated glomerular filtration rate (eGFR) decline after 4.8 years (median) follow-up. We used weighted correlation network analysis to determine proteins’ cellular enrichment in the kidney transcriptome (single-cell/nucleus RNA sequencing, spatial transcriptomics) in 20 patients with diverse causes of AKI who received research kidney biopsy from the Kidney Precision Medicine Project.

Results

The ASSESS-AKI patients had median (IQR) age of 67 (59-75) years and median (IQR) eGFR of 65 (41-85) ml/min/1.73m² at 3 months post-discharge. We identified 387 and 10 proteins associated with faster and slower eGFR decline, respectively (Fig. 1A), including 283 expressed by kidney cells and 114 not expressed. The expression formed 3 clusters enriched in the proximal tubule (Module 1 [M1], Fig.1B), degenerative tubule and myeloid cells (M2), and stromal cells (M3), and correlated with histopathological features of AKI, such as tubular injury, interstitial inflammation, and fibrosis (Fig.1C).

Conclusion

By integrating the urine proteome and kidney transcriptome, we identified degenerative tubular injury, inflammation, and fibrosis as pathways associated with eGFR decline in recently hospitalized patients.

Funding

• NIDDK Support