Kidney Week

Abstract: TH-OR075

Intrarenal CCL2 and CCR2 Activation Profiles Are Linked to Noninvasive Urinary Biomarkers Associated with Outcomes in Patients with FSGS

Session Information

• Glomerular Diseases: Novel Mechanisms of Injury
  October 22, 2026 | Location: Room 401, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Latt, Khun Zaw, University of Michigan, Ann Arbor, Michigan, United States

Khun Zaw Latt, MBBS, PhD

• White, Carl, Dimerix Bioscience Pty Ltd, Melbourne, Victoria, Australia

Carl White, PhD

• Hartman, John R., University of Michigan, Ann Arbor, Michigan, United States

John R. Hartman

• Fuller, David E., Dimerix Bioscience Pty Ltd, Melbourne, Victoria, Australia

David E. Fuller, PharmD, MBBS

• McCown, Phillip J., University of Michigan, Ann Arbor, Michigan, United States

Phillip J. McCown, MS, PhD

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

Wenjun Ju, PhD

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States

Sean Eddy, PhD

Background

Multiple lines of evidence indicate a role for C-C chemokine receptor 2 (CCR2) in the pathogenesis of focal segmental glomerulosclerosis (FSGS). In animal CKD models, CCR2 inhibition improves renal function. DMX-200 is a small molecule inhibitor of CCR2 signaling under development and currently being tested for efficacy in patients with FSGS in a Phase 3 clinical trial (ACTION3). This analysis was performed to determine prevalence of CCR2 activation in patients with FSGS.

Methods

We assessed CCR2 expression in single-nucleus RNAseq data from 28 patients with biopsy-proven FSGS and from tubulointerstitial bulk RNAseq profiles from 114 patients with biopsy-proven FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). Transcriptional profiles were used to develop a 205 gene signature consistent with CCR2 activation in transcriptional data and compute a CCR2 transcriptional activity (TA) score.

Results

CCR2 TA scores were elevated in patients with FSGS compared to healthy living transplant donors (p<0.001). CCR2 TA scores were negatively correlated with log₂eGFR (r=-0.5, p<0.0001) at time of biopsy and strongly correlated with mRNA expression of the CCR2 ligand, CCL2 (r=0.83, p<0.0001). CCR2 TA scores were also correlated with urinary MCP1 (the protein encoded by CCL2) normalized to creatinine (uMCP1/Cr) (r=0.37, p=0.0025). uMCP1/Cr was previously shown to associate with patient molecular clusters associated with progressive loss of kidney function (40% loss of eGFR or End Stage Renal Disease) in patients with FSGS.

Conclusion

A CCR2 activity profile was elevated in patients with FSGS and associated with elevated UPCR and lower eGFR. The CCR2 activity profile was consistent with urinary detection of MCP1, a marker for poor outcome in patients with FSGS. Taken together, these results suggest that a CCR2 TA score is supportive of targeting CCR2 in the Phase 3 ACTION3 study and potentially useful in prospectively identifying patients likely to respond to CCR2 targeted therapies.

Funding

• NIDDK Support – Dimerix Bioscience