Kidney Week

Abstract: SA-PO0323

Genetic Variation of Urinary Uromodulin in ASSESS-AKI

Session Information

• AKI: Epidemiology and Risk Factors
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Kiernan, Elizabeth, University of Washington, Seattle, Washington, United States

Elizabeth Kiernan, MD

• Stanaway, Ian Byrell, University of Washington, Seattle, Washington, United States

Ian Byrell Stanaway, PhD

• Zelnick, Leila R., University of Washington, Seattle, Washington, United States

Leila R. Zelnick, PhD, FASN

• de Boer, Ian, University of Washington, Seattle, Washington, United States

Ian de Boer, MD, MS

• Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Talat Alp Ikizler, MD, FASN

• Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Edward D. Siew, MD, MS, MSc

• Go, Alan S., The Permanente Medical Group Inc, Oakland, California, United States

Alan S. Go, MD

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

Steven G. Coca, DO, MS

• Wurfel, Mark M., University of Washington, Seattle, Washington, United States

Mark M. Wurfel, MD, PhD

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

Chirag R. Parikh, MD, PhD, FASN

• Himmelfarb, Jonathan, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Jonathan Himmelfarb, MD, FASN

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

Pavan K. Bhatraju, MD, MS

Background

Urine protein quantitative trait loci (u-pQTLs) map genetic variants that influence urine protein levels. Uromodulin is an 85 kD glycoprotein predominantly expressed by thick ascending limb (TAL) cells. Post-AKI levels have been linked to subsequent CKD development. Here, we sought to identify whether UMOD genetic variation is associated with urinary uromodulin levels at 3 and 12 months after hospitalization.

Methods

We conducted a GWAS of urine uromodulin in ASSESS-AKI, a multicenter, prospective study of hospitalized adults with and without AKI. All participants had to survive to 3-months after hospitalization to be included. The primary outcome was log₂-transformed urine uromodulin levels, measured in 1366 participants at 3 months and 1182 at 12 months. Genotyping was done using the Illumina MEGA platform with imputation to the HRC1.1. We tested associations of SNPs and protein levels adjusted for age, gender and principal components 1-10 using rfmix/TRACTOR for local ancestry GWAS.

Results

Among 1369 participants, 637 had AKI and 732 did not. Average age was 68.5 years (SD 13.1) and 33% were women. Relevant comorbities included CKD in 39% and diabetes in 49%. At 3 months, no SNPs reached genome wide significance. At 12 months, a gene locus in the UMOD gene at chromosome 16 was associated with urinary uromodulin levels. The variant with strongest association with urinary uromodulin was rs34262842 (G minor allele frequency=0.17; beta=-0.376, se=0.059 p=2.76x10^-10) (Figure 1). Each minor allele was associated with 752pg/mL lowering and explains ~2.2% of the variance in urinary uromodulin levels. Similar results were found normalizing uromodulin by urinary creatinine.

Conclusion

No variants were shown to regulate urine uromodulin levels 3 months after hospitalization, suggesting a heavier influence of environmental factors. However, at 12 months in a smaller population of the same surviving people, we identified a genome wide significant variant in UMOD associated with urinary uromodulin levels that could enable future analyses to determine whether uromodulin is causal in the transition from AKI to CKD.

Figure 1. GWAS of 12-month Urinary Uromodulin A. Manhattan Plot B. Difference in Urinary Uromodulin Level by rs34262842

Funding

• NIDDK Support