04788nas a2200637 4500008004100000022001400041245011400055210006900169260001600238300001400254490000800268520300400276653001003280653000903290653002203299653001903321653001503340653002403355653002703379653001103406653003103417653001103448653002803459653000903487653001603496653002103512653000903533100001803542700002903560700002503589700001903614700002403633700002303657700002003680700002303700700002103723700002303744700002003767700002103787700002103808700001703829700001803846700001903864700002203883700002003905700002203925700001803947700001903965700001903984700002104003700002104024700002504045700002304070700002104093856003604114 2014 eng d a1538-359800aDecline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.0 aDecline in estimated glomerular filtration rate and subsequent r c2014 Jun 25 a2518-25310 v3113 a

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.

OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.

DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.

DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.

MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.

RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.

CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

10aAdult10aAged10aAged, 80 and over10aCohort Studies10aCreatinine10aDisease Progression10aEndpoint Determination10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aReference Values10aRisk1 aCoresh, Josef1 aTurin, Tanvir, Chowdhury1 aMatsushita, Kunihiro1 aSang, Yingying1 aBallew, Shoshana, H1 aAppel, Lawrence, J1 aArima, Hisatomi1 aChadban, Steven, J1 aCirillo, Massimo1 aDjurdjev, Ognjenka1 aGreen, Jamie, A1 aHeine, Gunnar, H1 aInker, Lesley, A1 aIrie, Fujiko1 aIshani, Areef1 aIx, Joachim, H1 aKovesdy, Csaba, P1 aMarks, Angharad1 aOhkubo, Takayoshi1 aShalev, Varda1 aShankar, Anoop1 aWen, Chi, Pang1 ade Jong, Paul, E1 aIseki, Kunitoshi1 aStengel, Bénédicte1 aGansevoort, Ron, T1 aLevey, Andrew, S uhttps://chs-nhlbi.org/node/655404500nas 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