03482nas a2200541 4500008004100000022001400041245011500055210006900170260001300239300001200252490000700264520194200271653002402213653001502237653001002252653002202262653002102284653000902305653001602314653003402330653004002364653001102404653003102415653001102446653001402457653000902471653001602480653003002496653001402526653003002540653002102570653001602591100002102607700001902628700002402647700002302671700001702694700002202711700001902733700001802752700002002770700001802790700002002808700002502828700002202853710002902875856003602904 2015 eng d a1523-683800aA Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.0 aMetaanalysis of the Association of Estimated GFR Albuminuria Age c2015 Oct a591-6010 v663 a

BACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).

STUDY DESIGN: Collaborative meta-analysis.

SETTING & POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).

SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events.

PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions.

OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.

LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.

CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

10aAcute Kidney Injury10aAdolescent10aAdult10aAfrican Americans10aAge Distribution10aAged10aAlbuminuria10aContinental Population Groups10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aSeverity of Illness Index10aSex Distribution10aYoung Adult1 aGrams, Morgan, E1 aSang, Yingying1 aBallew, Shoshana, H1 aGansevoort, Ron, T1 aKimm, Heejin1 aKovesdy, Csaba, P1 aNaimark, David1 aOien, Cecilia1 aSmith, David, H1 aCoresh, Josef1 aSarnak, Mark, J1 aStengel, Bénédicte1 aTonelli, Marcello1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/679704500nas a2200337 4500008004100000022001400041245014900055210006900204260001300273300001200286490000600298520343400304100002503738700002403763700001803787700002003805700001903825700002103844700001903865700002203884700001703906700002403923700002503947700002303972700002203995700001804017700001904035700002404054710004804078856003604126 2017 eng d a2213-859500aMeasures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.0 aMeasures of chronic kidney disease and risk of incident peripher c2017 Sep a718-7280 v53 a

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.

1 aMatsushita, Kunihiro1 aBallew, Shoshana, H1 aCoresh, Josef1 aArima, Hisatomi1 aArnlöv, Johan1 aCirillo, Massimo1 aEbert, Natalie1 aHiramoto, Jade, S1 aKimm, Heejin1 aShlipak, Michael, G1 aVisseren, Frank, L J1 aGansevoort, Ron, T1 aKovesdy, Csaba, P1 aShalev, Varda1 aWoodward, Mark1 aKronenberg, Florian1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/7575