Measures of chronic kidney disease and risk of incident peripheral artery disease

a collaborative meta-analysis of individual participant data

Chronic Kidney Disease Prognosis Consortium

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background 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. Methods 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. Findings 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. Interpretation 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. Funding American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

Original languageEnglish (US)
Pages (from-to)718-728
Number of pages11
JournalThe Lancet Diabetes and Endocrinology
Volume5
Issue number9
DOIs
StatePublished - Sep 1 2017

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Peripheral Arterial Disease
Chronic Renal Insufficiency
Meta-Analysis
Glomerular Filtration Rate
Creatinine
Albumins
Amputation
Albuminuria
Proteinuria
Leg
Incidence
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Intermittent Claudication
Proportional Hazards Models
Signs and Symptoms
Lower Extremity

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Measures of chronic kidney disease and risk of incident peripheral artery disease : a collaborative meta-analysis of individual participant data. / Chronic Kidney Disease Prognosis Consortium.

In: The Lancet Diabetes and Endocrinology, Vol. 5, No. 9, 01.09.2017, p. 718-728.

Research output: Contribution to journalArticle

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title = "Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data",
abstract = "Background 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. Methods 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. Findings 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. Interpretation 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. Funding American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.",
author = "{Chronic Kidney Disease Prognosis Consortium} and Kunihiro Matsushita and Ballew, {Shoshana H.} and Josef Coresh and Hisatomi Arima and Johan {\"A}rnl{\"o}v and Massimo Cirillo and Natalie Ebert and Hiramoto, {Jade S.} and Heejin Kimm and Shlipak, {Michael G.} and Visseren, {Frank L.J.} and Gansevoort, {Ron T.} and Kovesdy, {Csaba P.} and Csaba Kovesdy and Mark Woodward and Florian Kronenberg and John Chalmers and Vlado Perkovic and Grams, {Morgan E.} and Yingying Sang and Elke Schaeffner and Peter Martus and Adeera Levin and Ognjenka Djurdjev and Mila Tang and Gunnar Heine and Sarah Seiler and Adam Zawada and Insa Emrich and Mark Sarnak and Ronit Katz and Hermann Brenner and Ben Sch{\"o}ttker and Dietrich Rothenbacher and Saum, {Kai Uwe} and Anna K{\"o}ttgen and Markus Schneider and Eckardt, {Kai Uwe} and Jamie Green and Kirchner, {H. Lester} and Chang, {Alex R.} and Corri Black and Angharad Marks and Gordon Prescott and Laura Clark and Nick Fluck and Jee, {Sun Ha} and Yejin Mok and Gabriel Chodick and Wetzels, {Jack F.M.}",
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TY - JOUR

T1 - Measures of chronic kidney disease and risk of incident peripheral artery disease

T2 - a collaborative meta-analysis of individual participant data

AU - Chronic Kidney Disease Prognosis Consortium

AU - Matsushita, Kunihiro

AU - Ballew, Shoshana H.

AU - Coresh, Josef

AU - Arima, Hisatomi

AU - Ärnlöv, Johan

AU - Cirillo, Massimo

AU - Ebert, Natalie

AU - Hiramoto, Jade S.

AU - Kimm, Heejin

AU - Shlipak, Michael G.

AU - Visseren, Frank L.J.

AU - Gansevoort, Ron T.

AU - Kovesdy, Csaba P.

AU - Kovesdy, Csaba

AU - Woodward, Mark

AU - Kronenberg, Florian

AU - Chalmers, John

AU - Perkovic, Vlado

AU - Grams, Morgan E.

AU - Sang, Yingying

AU - Schaeffner, Elke

AU - Martus, Peter

AU - Levin, Adeera

AU - Djurdjev, Ognjenka

AU - Tang, Mila

AU - Heine, Gunnar

AU - Seiler, Sarah

AU - Zawada, Adam

AU - Emrich, Insa

AU - Sarnak, Mark

AU - Katz, Ronit

AU - Brenner, Hermann

AU - Schöttker, Ben

AU - Rothenbacher, Dietrich

AU - Saum, Kai Uwe

AU - Köttgen, Anna

AU - Schneider, Markus

AU - Eckardt, Kai Uwe

AU - Green, Jamie

AU - Kirchner, H. Lester

AU - Chang, Alex R.

AU - Black, Corri

AU - Marks, Angharad

AU - Prescott, Gordon

AU - Clark, Laura

AU - Fluck, Nick

AU - Jee, Sun Ha

AU - Mok, Yejin

AU - Chodick, Gabriel

AU - Wetzels, Jack F.M.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background 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. Methods 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. Findings 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. Interpretation 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. Funding American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

AB - Background 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. Methods 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. Findings 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. Interpretation 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. Funding American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

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U2 - 10.1016/S2213-8587(17)30183-3

DO - 10.1016/S2213-8587(17)30183-3

M3 - Article

VL - 5

SP - 718

EP - 728

JO - The Lancet Diabetes and Endocrinology

JF - The Lancet Diabetes and Endocrinology

SN - 2213-8587

IS - 9

ER -