@article {6554, title = {Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.}, journal = {JAMA}, volume = {311}, year = {2014}, month = {2014 Jun 25}, pages = {2518-2531}, abstract = {

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.

}, keywords = {Adult, Aged, Aged, 80 and over, Cohort Studies, Creatinine, Disease Progression, Endpoint Determination, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Reference Values, Risk}, issn = {1538-3598}, doi = {10.1001/jama.2014.6634}, author = {Coresh, Josef and Turin, Tanvir Chowdhury and Matsushita, Kunihiro and Sang, Yingying and Ballew, Shoshana H and Appel, Lawrence J and Arima, Hisatomi and Chadban, Steven J and Cirillo, Massimo and Djurdjev, Ognjenka and Green, Jamie A and Heine, Gunnar H and Inker, Lesley A and Irie, Fujiko and Ishani, Areef and Ix, Joachim H and Kovesdy, Csaba P and Marks, Angharad and Ohkubo, Takayoshi and Shalev, Varda and Shankar, Anoop and Wen, Chi Pang and de Jong, Paul E and Iseki, Kunitoshi and Stengel, B{\'e}n{\'e}dicte and Gansevoort, Ron T and Levey, Andrew S} } @article {6797, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {591-601}, abstract = {

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.

}, keywords = {Acute Kidney Injury, Adolescent, Adult, African Americans, Age Distribution, Aged, Albuminuria, Continental Population Groups, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Young Adult}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.337}, author = {Grams, Morgan E and Sang, Yingying and Ballew, Shoshana H and Gansevoort, Ron T and Kimm, Heejin and Kovesdy, Csaba P and Naimark, David and Oien, Cecilia and Smith, David H and Coresh, Josef and Sarnak, Mark J and Stengel, B{\'e}n{\'e}dicte and Tonelli, Marcello} } @article {7575, title = {Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.}, journal = {Lancet Diabetes Endocrinol}, volume = {5}, year = {2017}, month = {2017 Sep}, pages = {718-728}, 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{\textperiodcentered}4 years [IQR 5{\textperiodcentered}7-8{\textperiodcentered}9], range 2{\textperiodcentered}0-15{\textperiodcentered}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{\textperiodcentered}73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1{\textperiodcentered}22 (95\% CI 1{\textperiodcentered}14-1{\textperiodcentered}30) at an eGFR of 45 mL/min per 1{\textperiodcentered}73 m2 and 2{\textperiodcentered}06 (1{\textperiodcentered}70-2{\textperiodcentered}48) at an eGFR of 15 mL/min per 1{\textperiodcentered}73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1{\textperiodcentered}50 (1{\textperiodcentered}41-1{\textperiodcentered}59) at an ACR of 30 mg/g and 2{\textperiodcentered}28 (2{\textperiodcentered}12-2{\textperiodcentered}44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3{\textperiodcentered}68 (95\% CI 3{\textperiodcentered}00-4{\textperiodcentered}52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5{\textperiodcentered}76 [4{\textperiodcentered}90-6{\textperiodcentered}77] for incident peripheral artery disease and 10{\textperiodcentered}61 [5{\textperiodcentered}70-19{\textperiodcentered}77] for amputation in eGFR <30 mL/min per 1{\textperiodcentered}73 m2 plus ACR >=300 mg/g or dipstick proteinuria 2+ or higher vs eGFR >=90 mL/min per 1{\textperiodcentered}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{\textperiodcentered}058, 95\% CI 0{\textperiodcentered}045-0{\textperiodcentered}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.

}, issn = {2213-8595}, doi = {10.1016/S2213-8587(17)30183-3}, author = {Matsushita, Kunihiro and Ballew, Shoshana H and Coresh, Josef and Arima, Hisatomi and Arnl{\"o}v, Johan and Cirillo, Massimo and Ebert, Natalie and Hiramoto, Jade S and Kimm, Heejin and Shlipak, Michael G and Visseren, Frank L J and Gansevoort, Ron T and Kovesdy, Csaba P and Shalev, Varda and Woodward, Mark and Kronenberg, Florian} } @article {9637, title = {Development and Validation of the American Heart Association{\textquoteright}s PREVENT Equations.}, journal = {Circulation}, volume = {149}, year = {2024}, month = {2024 Feb 06}, pages = {430-449}, abstract = {

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD.

METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets.

RESULTS: Among 6 612 004 adults included, mean{\textpm}SD age was 53{\textpm}12 years, and 56\% were women. Over a mean{\textpm}SD follow-up of 4.8{\textpm}3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; =0.01).

CONCLUSIONS: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.

}, keywords = {Adult, Aged, Albumins, American Heart Association, Atherosclerosis, Cardiovascular Diseases, Creatinine, Female, Glycated Hemoglobin, Heart Failure, Humans, Male, Middle Aged, Risk Assessment, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.123.067626}, author = {Khan, Sadiya S and Matsushita, Kunihiro and Sang, Yingying and Ballew, Shoshana H and Grams, Morgan E and Surapaneni, Aditya and Blaha, Michael J and Carson, April P and Chang, Alexander R and Ciemins, Elizabeth and Go, Alan S and Gutierrez, Orlando M and Hwang, Shih-Jen and Jassal, Simerjot K and Kovesdy, Csaba P and Lloyd-Jones, Donald M and Shlipak, Michael G and Palaniappan, Latha P and Sperling, Laurence and Virani, Salim S and Tuttle, Katherine and Neeland, Ian J and Chow, Sheryl L and Rangaswami, Janani and Pencina, Michael J and Ndumele, Chiadi E and Coresh, Josef} }