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Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.

TitleMeasures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.
Publication TypeJournal Article
Year of Publication2017
AuthorsMatsushita, K, Ballew, SH, Coresh, J, Arima, H, Arnlöv, J, Cirillo, M, Ebert, N, Hiramoto, JS, Kimm, H, Shlipak, MG, Visseren, FLJ, Gansevoort, RT, Kovesdy, CP, Shalev, V, Woodward, M, Kronenberg, F
Corporate/Institutional AuthorsChronic Kidney Disease Prognosis Consortium,
JournalLancet Diabetes Endocrinol
Volume5
Issue9
Pagination718-728
Date Published2017 Sep
ISSN2213-8595
Abstract<p><b>BACKGROUND: </b>Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.</p><p><b>METHODS: </b>In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.</p><p><b>FINDINGS: </b>We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups.</p><p><b>INTERPRETATION: </b>Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.</p><p><b>FUNDING: </b>American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.</p>
DOI10.1016/S2213-8587(17)30183-3
Alternate JournalLancet Diabetes Endocrinol
PubMed ID28716631
PubMed Central IDPMC5649254
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
N01 HC095164 / HC / NHLBI NIH HHS / United States
N01 HC095166 / HC / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 AG007181 / AG / NIA NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
R01 DK031801 / DK / NIDDK NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
N01 HC095169 / HC / NHLBI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
N01 HC095163 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 DK100446 / DK / NIDDK NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
ePub date: 
17/09