Kidney Week

Abstract: SA-PO0937

Lower Urine Uromodulin Associated with Higher Interstitial Fibrosis and Tubular Atrophy on Kidney Biopsy: A Multicohort Study

Session Information

• Pathology: Updates and Insights
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Parikh, Manav C., University of Pennsylvania School of Arts & Sciences, Philadelphia, Pennsylvania, United States

Manav C. Parikh

• Xue, Jiashu, Johns Hopkins Medicine, Baltimore, Maryland, United States

Jiashu Xue, MSc

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

Heather Thiessen Philbrook

• Hu, David, Johns Hopkins Medicine, Baltimore, Maryland, United States

David Hu, MS

• Bitzel, Jack, Johns Hopkins Medicine, Baltimore, Maryland, United States

Jack Bitzel

• Rosenberg, Avi Z., Johns Hopkins Medicine, Baltimore, Maryland, United States

Avi Z. Rosenberg, MD, PhD

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

Dennis G. Moledina, MD, PhD, FASN

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

Steven G. Coca, DO, MS

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

Chirag R. Parikh, MD, PhD, FASN

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

Steven Menez, MD

Group or Team Name

• For the Kidney Precision Medicine Project (KPMP).

Background

Interstitial fibrosis and tubular atrophy (IFTA) are histological features associated with poor kidney outcomes. Urine uromodulin (uUMOD) is the most abundant protein produced by the thick ascending limb and is a biomarker of kidney health. We sought to investigate the relationship between uUMOD and the degree of IFTA on kidney biopsy.

Methods

uUMOD and urine creatinine were measured using the Meso Scale Discovery Platform in 200 participants who underwent native kidney biopsy at the Johns Hopkins Hospital between 2020-2023 under the Novel Approaches in the Investigation of Kidney Disease (NAIKiD) Study, and in 111 participants across 13 sites in the Kidney Precision Medicine Project (KPMP). 112 (56%) patients in the NAIKiD cohort and 27 (24.3%) in KPMP were biopsied as inpatients, and the rest as outpatients. The primary exposure was uUMOD indexed to urine creatinine (uUMOD:Cr). The degree of IFTA (<10%, 10-50%, >50%) was determined on clinical pathology reports in NAIKiD and through rigorous adjudication in the KPMP. Clinical adjustment variables included eGFR, UACR, diabetes, and hypertension. Both biomarkers were measured using the same protocol and batch of reagents for both cohorts in the JHU biomarker laboratory.

Results

In the NAIKiD cohort, 22% of patients had <10% IFTA, 51% had 10-50% IFTA, and 27% had >50% IFTA. In KPMP, 24.3% had <10% IFTA, 64.0% had 10-50% IFTA, and 11.7% had >50% IFTA. Across both cohorts, median uUMOD (ug/mL) and uUMOD:Cr (ug/mg) were lower with increasing IFTA (Figure 1). Each doubling of uUMOD:Cr was significantly associated with lower odds of IFTA in both cohorts (adjusted odds ratio (95% CI) of 0.81 (0.66-0.998) in NAIKID, adjusted OR of 0.56 (0.40-0.78) in KPMP; Table 1).

Conclusion

Urine UMOD was robustly inversely associated with IFTA on kidney biopsy. Future studies should combine clinical variables and multiple biomarkers to develop non-invasive scores for kidney fibrosis assessment.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20258jenm2q5