title: Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.
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 m(2), 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.
authors: Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California; joeix@ucsd.edu.
authors: Joachim H
authors: JH
authors: Ix
authors: Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Washington;
authors: Mary L
authors: ML
authors: Biggs
authors: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts;
authors: Kenneth
authors: K
authors: Mukamal
authors: Division of Aging, Brigham and Women's Hospital and Boston Veterans Affairs Healthcare System, Boston, Massachusetts;
authors: Luc
authors: L
authors: Djousse
authors: New York Academy of Medicine, New York, New York;
authors: David
authors: D
authors: Siscovick
authors: Department of Pathology, University of Vermont, Burlington, Vermont;
authors: Russell
authors: R
authors: Tracy
authors: Division of Nephrology, University of Washington, Seattle, Washington;
authors: Ronit
authors: R
authors: Katz
authors: Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington;
authors: Joseph A
authors: JA
authors: Delaney
authors: Department of Medicine, Florida International University, Miami, Florida;
authors: Paulo
authors: P
authors: Chaves
authors: Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California;
authors: Dena E
authors: DE
authors: Rifkin
authors: Department of Family and Preventive Medicine, University of California San Diego, San Diego, California;
authors: Jan M
authors: JM
authors: Hughes-Austin
authors: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
authors: Pranav S
authors: PS
authors: Garimella
authors: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
authors: Mark J
authors: MJ
authors: Sarnak
authors: Department of Medicine, University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California; and.
authors: Michael G
authors: MG
authors: Shlipak
authors: Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors: Jorge R
authors: JR
authors: Kizer
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000652:urine; D008297:Male; D010446:Peptide Fragments / Q000652:urine*; D011347:Procollagen / Q000652:urine*; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000652:urine*
chemical_list: D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide
keywords: cells; fibrosis; geriatric nephrology; progression of chronic renal failure; tubule
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