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Kidney Week

Abstract: TH-PO428

Association of Urine Biomarkers of Kidney Tubule Health with Incident CKD in the REGARDS Cohort

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Greenberg, Jason Henry, Yale University, Woodbridge, Connecticut, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Schrauben, Sarah J., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
  • Ramachandran, Vasan S., Boston University School of Medicine, Framingham, Massachusetts, United States
  • Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Schelling, Jeffrey R., Case Western Reserve University, Cleveland, Ohio, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Gutierrez, Orlando M., UAB School of Medicine, Birmingham, Alabama, United States

Novel biomarkers have been identified that associate with the onset or progression of CKD in specific populations. Within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, we evaluated whether 5 proteins, measured in stored urine specimens, were associated with the subsequent development of CKD among persons without diabetes at baseline.


The REGARDS Study recruited Black and White participants from the continental US with emphasis on the Southeast US stroke belt. Candidate participants for this ancillary study had a baseline estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73m2, had a stored urine specimen from baseline, and eGFR repeated at the follow-up visit 9 years later. Incident CKD was defined as the onset of an eGFR <60 ml/min/1.73m2 and a ≥40% decline in eGFR. The case-cohort design included a subcohort of 493 individuals, among whom 57 developed incident CKD, and 431 additional cases of incident CKD. Weighted multivariable proportional hazards analyses modeled biomarkers both as continuous variables (log2) and in quartiles.


The mean age of the subcohort was 63±8 years, 58% were women, and 30% were Black; mean (SD) eGFR was 89±14 ml/min/1.73m2 and median (IQR) albumin-to-creatinine ratio was 6.1 (4.2- 9.7) mg/g. In unadjusted models, only higher urine EGF was associated with incident CKD (HR per two-fold increment 1.20; 95% CI: 1.02-1.41); this association was attenuated after adjustment. No other biomarker approached statistical significance in any analysis (Table).


Among REGARDS Study participants without diabetes or CKD at baseline, none of the 5 urine biomarkers studied was independently associated with incident CKD

Quartiles of Urine Biomarkers and Incident CKD in REGARDS
Urine BiomarkerQ1 HR (95% CI)Q2 HR (95% CI)Q3 HR (95% CI)Q4 HR (95% CI)
KIM-11.00 (ref)0.97 (0.59, 1.59)0.80 (0.47, 1.37)0.71 (0.40, 1.28)
MCP-11.00 (ref)0.96 (0.57, 1.61)0.76 (0.41, 1.38)0.86 (0.43, 1.71)
EGF1.00 (ref)0.93 (0.58, 1.48)1.35 (0.84, 2.18)1.49 (0.91, 2.42)
YKL-401.00 (ref)1.11 (0.71, 1.74)1.36 (0.86, 2.13)1.07 (0.67, 1.72)
α-1 microglobulin1.00 (ref)0.84 (0.53,1 .34)0.98 (0.61, 1.59)1.30 (0.77, 2.20)

Adjusted for age, sex, race, education, urine creatinine, BMI, SBP, HTN meds, smoking, CHD, stroke, urine albumin & eGFR.


  • NIDDK Support