Urine collagen fragments and CKD progression- the cardiovascular health study

Joachim H. Ix, Mary L. Biggs, Kenneth Mukamal, Luc Djousse, David Siscovick, Russell Tracy, Ronit Katz, Joseph A. Delaney, Paulo Chaves, Dena E. Rifkin, Jan M. Hughes-Austin, Pranav S. Garimella, Mark J. Sarnak, Michael G. Shlipak, Jorge Kizer

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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 (6SD) was 7865 years, mean eGFR was 63618 ml/min per 1.73 m2, and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) mg/L. In a case-control study (192 participants, 231 controls), each doubling of urinePIIINP associatedwith22%higherodds ofCKDprogression(adjustedoddsratio, 1.22;95%confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associatedwith 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.

Original languageEnglish (US)
Pages (from-to)2494-2503
Number of pages10
JournalJournal of the American Society of Nephrology
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2015

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ASJC Scopus subject areas

  • Nephrology

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Ix, J. H., Biggs, M. L., Mukamal, K., Djousse, L., Siscovick, D., Tracy, R., Katz, R., Delaney, J. A., Chaves, P., Rifkin, D. E., Hughes-Austin, J. M., Garimella, P. S., Sarnak, M. J., Shlipak, M. G., & Kizer, J. (2015). Urine collagen fragments and CKD progression- the cardiovascular health study. Journal of the American Society of Nephrology, 26(10), 2494-2503. https://doi.org/10.1681/ASN.2014070696