Kidney Week

Abstract: FR-OR041

Plasma Proteomic-Derived Signature of the Histopathologic Chronicity Score and the Risk of Kidney Failure

Session Information

• Exciting Developments in CKD Research: From Diagnostics to Management and More
  October 23, 2026 | Location: Mile High Ballroom 1D, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Abbasi, Momen, University of Illinois Chicago, Chicago, Illinois, United States

Momen Abbasi, MD

• Missikpode, Celestin, University of Illinois Chicago, Chicago, Illinois, United States

Celestin Missikpode, PhD

• Ju, Wenjun, University of Michigan, Ann Arbor, Michigan, United States

Wenjun Ju, PhD

• Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin, MD, PhD

• Ricardo, Ana C., University of Illinois Chicago, Chicago, Illinois, United States

Ana C. Ricardo, MD, MS, MPH, FASN

• Schmidt, Insa Marie, Boston Medical Center, Boston, Massachusetts, United States

Insa Marie Schmidt, MD, MPH

• Setty, Suman, University of Illinois Chicago, Chicago, Illinois, United States

Suman Setty, MBBS, PhD

• Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States

Sushrut S. Waikar, MD, MPH

• Lash, James P., University of Illinois Chicago, Chicago, Illinois, United States

James P. Lash, MD, FASN

• Srivastava, Anand, University of Illinois Chicago, Chicago, Illinois, United States

Anand Srivastava, MD, MPH

Group or Team Name

• Kidney Precision Medicine Project, Chronic Renal Insufficiency Cohort

Background

Clinical biomarkers cannot adequately capture overall chronic damage burden in kidney biopsy specimens. We tested whether a plasma proteomics signature identifies a histopathologic chronicity score and is associated with future risk of ESKD.

Methods

We profiled ~5,000 plasma proteins, measured by SomaLogic, and derived a histopathologic chronicity score from adjudicated kidney biopsy specimens in 157 Kidney Precision Medicine Project (KPMP) participants with diabetes or hypertension-related CKD. We developed a proteomics chronicity score (PCS) using LASSO regression. We compared the area under the curve (AUC) of a base clinical model to a model further including the PCS to predict the chronicity score. Proportional hazards models tested associations of the PCS with subsequent ESKD in 3090 Chronic Renal Insufficiency Cohort (CRIC) Study participants with overlapping SomaLogic proteins. We explored tissue expression of candidate proteins using regional proteomics, transcriptomics, single-nucleus and single-cell RNA sequencing using the KPMP Tissue Atlas.

Results

The PCS had 24 proteins, which correlated strongly with the chronicity score (Rp=0.78, Figure 1A) and improved discrimination of advanced chronic changes (score ≥5) above variables included in the kidney failure risk equation (Figure 1B). During a median follow-up of 10.2 years (IQR, 4.4–15.9), 1044 CRIC participants progressed to ESKD. The PCS was independently associated with future ESKD [HR 1.39, (95% CI 1.24-1.56) (Figure 1C). Six proteins showed consistent glomerular or tubulointerstitial tissue-based expression (Figure 1D).

Conclusion

A non-invasive PCS improves detection of overall chronic damage burden and is associated with progression to ESKD. Candidate proteins revealed consistent glomerular or tubulointerstitial expression that may translate into therapeutic targets.

Funding

• NIDDK Support