Kidney Week

Abstract: SA-PO306

Urine Biomarkers for Diabetic Kidney Disease Progression

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Schrauben, Sarah J., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Sarah J. Schrauben, MD, MS

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States

Michael Shlipak, MD, MPH

• Dobre, Mirela A., Case Western Reserve University, Cleveland, Ohio, United States

Mirela A. Dobre, MD, FASN, MPH

• Gutierrez, Orlando M., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States

Orlando M. Gutierrez, MD

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak, MD, MS

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

Ana C. Ricardo, MD, MS, MPH, FASN

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

Steven G. Coca, DO, MS

• Greenberg, Jason Henry, Yale University School of Medicine, New Haven, Connecticut, United States

Jason Henry Greenberg, MD, FASN

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

Sushrut S. Waikar, MD, MPH

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

Chirag R. Parikh, MD, PhD, FASN

• Cohen, Debbie L., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Debbie L. Cohen, 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

• Taliercio, Jonathan J., Cleveland Clinic, Cleveland, Ohio, United States

Jonathan J. Taliercio, DO, FASN

• Schelling, Jeffrey R., Case Western Reserve University, Cleveland, Ohio, United States

Jeffrey R. Schelling, MD

• Rao, Panduranga S., University of Michigan, Ann Arbor, Michigan, United States

Panduranga S. Rao, MD, MBBS, MS

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

Paul L. Kimmel, MD, FASN

• Bonventre, Joseph V., Brigham and Women's Hospital Department of Medicine, Boston, Massachusetts, United States

Joseph V. Bonventre, MD, PhD, FASN

Background

Urine biomarkers of proximal and distal kidney tubular health and inflammation may provide non-invasive ways to identify individuals with diabetes at risk for CKD progression since the extent of tubulointerstitial pathology is related to diabetic kidney disease progression. Prior studies were limited by use of incidence of end-stage kidney disease as an endpoint, focus on fewer biomarkers, and inconsistent findings.

Methods

We performed a case-cohort study among 898 participants in the Chronic Renal Insufficiency Cohort (CRIC). The subcohort (N=599) comprised a group of randomly selected CRIC participants with diabetes and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m² with urine samples assayed for biomarkers. Cases (N=540) were participants with diabetes whose CKD progressed (incident ESKD or ≥40% eGFR decline). Urine biomarkers were assayed 1 yr after enrollment: monocyte chemoattractant protein-1 [MCP-1], kidney injury molecule-1 [KIM-1], a1-microglobulin, epidermal growth factor [EGF], and uromodulin. Weighted Cox regression models related biomarkers, standardized to urine creatinine (transformed as log₂), with CKD progression and were adjusted for covariates, including eGFR and urine albumin-to-creatinine ratio (UACR).

Results

KIM-1/Cr, MCP-1/Cr, and UACR were most strongly correlated (rho = 0.47 - 0.58). In fully adjusted models, KIM-1/Cr was associated with increased CKD progression (HR 1.16 per 2-fold higher, 95% CI 1.05-1.29) and EGF/Cr was associated with decreased risk of CKD progression (HR 0.83 per 2-fold higher, 95% CI: 0.73-0.95) The highest quartiles of KIM-1/Cr and MCP-1/Cr, compared to the lowest quartile, were associated with increased CKD progression (HR 1.69, 95% 1.14-2.51, and HR 1.65, 95% CI 1.11-2.47, respectively). The highest quartile of EGF/Cr, compared to lowest, was protective against CKD progression (HR 0.59, 95% CI: 0.41-0.85).

Conclusion

Urine MCP-1, KIM-1, and EGF may provide non-invasive ways to assess tubule and interstitial disease and health in diabetes and help identify those at higher risk of CKD progression independent of GFR and albuminuria, and aid in the clinical monitoring of individuals with CKD and diabetes.

Funding

• NIDDK Support