Clinical EpidemiologyUrine Collagen Fragments and CKD Progression—The Cardiovascular Health StudyIx, Joachim H.*; Biggs, Mary L.†; Mukamal, Kenneth‡; Djousse, Luc§; Siscovick, David‖; Tracy, Russell¶; Katz, Ronit**; Delaney, Joseph A.††; Chaves, Paulo‡‡; Rifkin, Dena E.*; Hughes-Austin, Jan M.§§; Garimella, Pranav S.‖‖; Sarnak, Mark J.‖‖; Shlipak, Michael G.¶¶; Kizer, Jorge R.*** Author Information *Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California; †Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; ‡Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts; §Division of Aging, Brigham and Women’s Hospital and Boston Veterans Affairs Healthcare System, Boston, Massachusetts; ‖New York Academy of Medicine, New York, New York; ¶Department of Pathology, University of Vermont, Burlington, Vermont; **Division of Nephrology, University of Washington, Seattle, Washington; ††Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; ‡‡Department of Medicine, Florida International University, Miami, Florida; §§Department of Family and Preventive Medicine, University of California San Diego, San Diego, California; ‖‖Division of Nephrology, Tufts Medical Center, Boston, Massachusetts; ¶¶Department of Medicine, University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California; and ***Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York Correspondence: Dr. Joachim H. Ix, Division of Nephrology-Hypertension, University of California San Diego, 3350 La Jolla Village Drive, Mail Code 9111-H, San Diego, CA 92161. Email: [email protected] Received July 21, 2014 Accepted December 22, 2014 Journal of the American Society of Nephrology 26(10):p 2494-2503, October 2015. | DOI: 10.1681/ASN.2014070696 Buy Metrics Abstract Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m2, and median urine PIIINP was 2.6 (interquartile range, 1.4–4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals. Copyright © 2015 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.