Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease

Chao Yang, Lucia Kwak, Shoshana H. Ballew, Pranav S. Garimella, Bernard G. Jaar, Aaron R. Folsom, Gerardo Heiss, Elizabeth Selvin, Pamela L. Lutsey, Josef Coresh, Kunihiro Matsushita

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background and aims Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. Methods Using data from 12,472 participants at baseline (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). Results During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3–8.3 for eGFR <30 and 2.4–3.5 for eGFR 30–59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91–3.54] for B2M vs. 1.20 [0.91–1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11–1.94] in top quartile). Conclusions Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

Original languageEnglish (US)
Pages (from-to)167-174
Number of pages8
StatePublished - Dec 2017

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts ( HHSN268201100005C , HHSN268201100006C , HHSN268201100007C , HHSN268201100008C , HHSN268201100009C , HHSN268201100010C , HHSN268201100011C , and HHSN268201100012C ). This specific project is supported by a grant from the National Kidney Foundation of Maryland (Professional Development Award 2014-2015) to Dr. Matsushita. Reagents for the β-2 microglobulin assay were donated by Roche Diagnostics.

Publisher Copyright:
© 2017 Elsevier B.V.


  • Bone-mineral metabolism markers
  • Kidney markers
  • Peripheral artery disease
  • Prospective cohort study


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