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JAMA. 2014 Jun 25;311(24):2518-2531. doi: 10.1001/jama.2014.6634.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

Collaborators (171)

Wright JT Jr, Appel LJ, Greene T, Astor BC, MacMahon S, Chalmers J, Arima H, Woodward M, Yatsuya H, Yamashita K, Toyoshima H, Tamakoshi K, Tonelli M, Hemmelgarn BR, James MT, Turin TC, Coresh J, Matsushita K, Grams M, Sang Y, Atkins RC, Polkinghorne KR, Chadban S, Shankar A, Klein R, Klein BE, Lee KE, Levin A, Djurdjev O, Tonelli M, Sacks FM, Curhan GC, Zawada AM, Rogacev KS, Seiler S, Heine GH, Navaneethan SD, Nally JV Jr, Schold JD, Shlipak M, Sarnak MJ, Katz R, Iso H, Kitamura A, Imano H, Yamagishi K, Wheeler DC, Emberson J, Townend JN, Landray MJ, Rothenbacher D, Brenner H, Müller H, Schöttker B, Fox CS, Hwang SJ, Meigs JB, Upadhyay A, Green J, Kirchner HL, Perkins R, Chang AR, Black C, Marks A, Fluck N, Prescott GJ, Cirillo M, Irie F, Iso H, Sairenchi T, Yamagishi K, Smith DH, Thorp ML, Johnson ES, Lee BJ, Guallar E, Ryu S, Chang Y, Cho J, Shin H, Chodick G, Shalev V, Birnbaum YC, Shainberg B, Wetzels JF, Blankestijn PJ, van Zuilen AD, Sarnak MJ, Levey AS, Inker LA, Menon V, Shlipak M, Sarnak M, Katz R, Peralta C, Ishani A, Neaton JD, Froissart M, Stengel B, Metzger M, Haymann JP, Houillier P, Flamant M, Elley CR, Kenealy T, Moyes SA, Collins JF, Drury P, Ohkubo T, Metoki H, Nakayama M, Kikuya M, Imai Y, Iseki K, Nelson RG, Knowler WC, Gansevoort RT, Bakker SJ, Hillege HL, van der Harst P, Jassal SK, Bergstrom J, Ix JH, Barrett-Connor E, Heerspink HJ, Brenner BE, de Zeeuw D, Jee SH, Kimm H, Mok Y, Tangri N, Sud M, Naimark D, Wen CP, Wen SF, Tsao CK, Tsai MK, Ärnlöv J, Lannfelt L, Larsson A, Kovesdy CP, Kalantar-Zadeh K, Bilo HJ, Kleefstra N, Groenier KH, Joosten H, Drion I, Coresh J, Gansevoort RT, de Jong PE, Iseki K, Levey AS, Matsushita K, Sarnak MJ, Stengel B, Warnock D, Woodward M, Ballew SH, Coresh J, Grams M, Matsushita K, Sang Y, Woodward M, Levey AS, Cheung AK, Coresh J, Lewis E, de Zeeuw D, Willis K, Stockbridge N, Thompson A.

Author information

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA (J Coresh, K Matsushita, Y Sang, SH Ballew); Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada (TC Turin); Johns Hopkins Medical Institutions, Baltimore, MD, 21205 (LJ Appel); The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia (H Arima); Department of Nephrology and Transplantation, Royal Prince Alfred Hospital, Sydney, NSW, Australia and Sydney Medical School, University of Sydney, Sydney, NSW, Australia (SJ Chadban); Department of Medicine, University of Salerno, Salerno, Italy (M Cirillo); BC Provincial Renal Agency, Vancouver, Canada (O Djurdjev); Nephrology Department, Geisinger Medical Center, Danville, PA, USA (JA Green); Department of Internal Medicine IV-Nephrology and Hypertension, Saarland University Medical Center, D-66421 Homburg, Germany (GH Heine); Division of Nephrology at Tufts Medical Center, Boston, MA 02111, USA (LA Inker, AS Levey); Department of Health and Welfare, Ibaraki Prefectural Office, Mito, Japan (F Irie); Minneapolis VA Health Care System and Department of Medicine, University of Minnesota, Minneapolis, MN, USA (A Ishani); University of California San Diego, San Diego, CA, USA (JH Ix); Memphis Veterans Affairs Medical Center and University of Tennessee Health Science Center, Memphis, TN, USA (CP Kovesdy); Division of Applied Health Sciences, University of Aberdeen, and NHS Grampian, Foresterhill, Aberdeen, UK (A Marks); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan, Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan, and Department of Health Science, Shiga University of Medical Science, Setatuskinowa, Otsu, Japan (T Ohkubo); Medical Informatics Department, Maccabi Healthcare Services, and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (V Shalev); Department of Family Medicine and Population Health, Virginia Commonwealth University, School of Medicine, 830 E. Main Street, P.O. Box 980212, Richmond, VA 23298-0212 (A Shankar); China Medical University Hospital, Taichung, Taiwan and Institute of Population Health Science, National Health Research Institutes, Zhunan, Taiwan (CP Wen); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands (PE de Jong, RT Gansevoort); Dialysis Unit, University Hospital of The Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan (K Iseki); Inserm U1018, CESP Center for Research in Epidemiology and Population Health, Villejuif, France and UMRS 1018, Paris-Sud University, Villejuif, France (B Stengel).
Contributed equally



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.


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.


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.


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.


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.


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.


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.

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