Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: A collaborative meta-analysis of individual participant data

Kunihiro Matsushita, Josef Coresh, Yingying Sang, John Chalmers, Caroline S. Fox, Eliseo Guallar, Tazeen Jafar, Simerjot K. Jassal, Gijs W.D. Landman, Paul Muntner, Paul Roderick, Toshimi Sairenchi, Ben Schöttker, Anoop Shankar, Michael Shlipak, Marcello Tonelli, Jonathan Townend, Arjan D. van Zuilen, Kazumasa Yamagishi, Kentaro YamashitaRon Gansevoort, Mark Sarnak, David G. Warnock, Mark Woodward, Johan ärnlöv, CKD Prognosis Consortium, Stephen MacMahon, Hisatomi Arima, Hiroshi Yatsuya, Hideaki Toyoshima, Koji Tamakoshi, Morgan Grams, Robert C. Atkins, Kevan R. Polkinghorne, Steven Chadban, Ronald Klein, Barbara E.K. Klein, Kristine E. Lee, Frank M. Sacks, Gary C. Curhan, Ronit Katz, Hiroyasu Iso, Akihiko Kitamura, Hironori Imano, Tazeen H. Jafar, Muhammad Islam, Juanita Hatcher, Neil Poulter, Nish Chaturvedi, David C. Wheeler, Jonathan Emberson, Jonathan N. Townend, Martin J. Landray, Hermann Brenner, Dietrich Rothenbacher, Heiko Müller, Caroline S. Fox, Shih Jen Hwang, James B. Meigs, Ashish Upadhyay, Jamie Green, H. Lester Kirchner, Robert Perkins, Alex R. Chang, Massimo Cirillo, Stein Hallan, Knut Aasarød, Cecilia M. Øien, Solfrid Romundstad, Fujiko Irie, Seungho Ryu, Yoosoo Chang, Juhee Cho, Hocheol Shin, Gabriel Chodick, Varda Shalev, Nachman Ash, Bracha Shainberg, Jack F.M. Wetzels, Peter J. Blankestijn, Arjan D. van Zuilen, Andrew S. Levey, Lesley A. Inker, Vandana Menon, Carmen Peralta, Dorothea Nitsch, Astrid Fletcher, Christopher Bulpitt, C. Raina Elley, Timothy Kenealy, Simon A. Moyes, John F. Collins, Paul Drury, Takayoshi Ohkubo, Hirohito Metoki, Masaaki Nakayama, Masahiro Kikuya, Yutaka Imai, Stephan J.L. Bakker, Hans L. Hillege, Hiddo J. Lambers Heerspink, Jaclyn Bergstrom, Joachim H. Ix, Elizabeth Barrett-Connor, Suzanne Judd, William McClellan, Orlando Gutierrez, Sun Ha Jee, Heejin Kimm, Yejin Mok, Navdeep Tangri, Maneesh Sud, David Naimark, Chi Pang Wen, Sung Feng Wen, Chwen Keng Tsao, Min Kuang Tsai, Johan ärnlöv, Lars Lannfelt, Anders Larsson, Henk J. Bilo, Nanne Kleefstra, Klaas H. Groenier, Hanneke Joosten, Iefke Drion, Paul E. de Jong, Kunitoshi Iseki, Benedicte Stengel, Shoshana H. Ballew

    Research output: Contribution to journalReview articlepeer-review

    268 Citations (Scopus)

    Abstract


    Background: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. Methods: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. Findings: The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. Interpretation: Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.

    Original languageEnglish
    Pages (from-to)514-525
    Number of pages12
    JournalThe Lancet Diabetes and Endocrinology
    Volume3
    Issue number7
    DOIs
    Publication statusPublished - Jul 2015

    Keywords

    • glomerular filtration rate
    • albuminuria
    • prediction of cardiovascular outcomes
    • collaborative meta-analysis
    • EGFR
    • Chronic Kidney Disease

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