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Cited by 988Chronic Kidney Disease and DiabetesAcute Kidney Injury ResearchDialysis and Renal Disease Management

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

Open access
Coresh, Josef, Turin, Tanvir Chowdhury, Matsushita, Kunihiro, Sang, Yingying, Ballew, Shoshana H., Appel, Lawrence J., Arima, Hisatomi, Chadban, Steven J. +19 more·2014·JAMA
DOI 10.1001/jama.2014.6634PMC PMC4172342
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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.

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  • The eGFR ≥57% decrease outcome was selected because it is a classic outcome in diabetic nephropathy studies and is a more robust kidney failure surrogate outcome than a ≥40% decrease in eGFR, particularly when initial changes in eGFR occur.

    “However, a sustained ≥57% decrease in eGFR (equivalent to doubling of serum creatinine) was selected in FIDELITY because it is a classic outcome in diabetic nephropathy studies2 , 12–14 and is a more robust kidney failure surrogate outcome than a ≥40% decrease in eGFR, particularly when initial changes in eGFR occur.14 , 15”

    From Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis (2022) · cites this paper as [14]

    The Background and Conclusions identify doubling of serum creatinine as an established CKD-progression endpoint equivalent to a 57% eGFR decline. The Discussion says acute treatment effects matter more for endpoints defined by smaller declines, supporting the rationale for a larger threshold. The paper does not specifically establish that this is a classic outcome in diabetic nephropathy studies or directly demonstrate that the 57% threshold is more robust than 40%. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Quantification of eGFR levels is essential for modifications of medication dosages or restrictions of use.

    “Quantification of eGFR levels is essential for modifications of medication dosages or restrictions of use (Fig. 11.1) (23,24)”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [24]

    The Methods (Procedures) explain how eGFR was calculated, and the Discussion relates eGFR decline to kidney failure and mortality risk. Neither addresses using eGFR levels to adjust medication doses or restrict medication use; searches for drug dosing and prescribing restrictions found no supporting passage. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 3

  1. [7]Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Kidney International Supplements 2013 3 1 1 150 30681074 PMC6341011
  2. [22]Inker LA Lambers Heerspink HJ Mondal H Coresh J Greene T Levey A GFR Decline as an Endpoint for Clinical Trials in CKD – A Meta-Analysis of Treatment Effects from Randomized Trials: Report of an NKF-FDA Workshop [Abstract] J Am Soc Nephrol 2013 24 12A
  3. [23]Greene T Teng C Ying J Validity and Statistical Power of Alternative eGFR-Based Endpoints: A Report from an NKF FDA Workshop [Abstract] J Am Soc Nephrol 2013 24 151A

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Authors
Coresh, J., Turin, T. C., Matsushita, K., Sang, Y., Ballew, S. H., Appel, L. J., Arima, H., Chadban, S. J., Cirillo, M., Djurdjev, O., Green, J. A., Heine, G. H., Inker, L. A., Irie, F., Ishani, A., Ix, J. H., Kovesdy, C. P., Marks, A., Ohkubo, T., Shalev, V., Shankar, A., Wen, C. P., de Jong, P. E., Iseki, K., Stengel, B., Gansevoort, R. T., & Levey, A. S.
Affiliations
  • Johns Hopkins University (US)
  • University of Calgary (CA)
  • The University of Sydney (AU)
  • Department of Medicine, University of Salerno, Salerno, Italy
  • BC Provincial Renal Agency, Vancouver, British Columbia, Canada
  • Geisinger Medical Center (US)
  • Saarland University (DE)
  • Tufts Medical Center (US)
  • Ibaraki Prefectural Government (JP)
  • University of Minnesota (US)
  • University of California San Diego (US)
  • University of Tennessee Health Science Center (US)
  • University of Aberdeen (GB)
  • Shiga University of Medical Science (JP)
  • Tel Aviv University (IL)
  • Virginia Commonwealth University (US)
  • National Health Research Institutes (TW)
  • Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • University of the Ryukyus University Hospital (JP)
  • Inserm U1018, CESP Center for Research in Epidemiology and Population Health and UMRS 1018, Paris-Sud University, Villejuif, France
  • University Medical Center Groningen (NL)
Corresponding author
Coresh, Josef
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2014-06-25
Volume
311
Issue
24
Pages
2518
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2014.6634
PMC
PMC4172342
OpenAlex
W1981055539
Semantic Scholar
769291f4736bc84ed171451f9eb9afdd77ff42b9
Cited by
988
References
36
Citations by year
2026: 59 · 2025: 76 · 2024: 62 · 2023: 88 · 2022: 84 · 2021: 89 · 2020: 91 · 2019: 88 · 2018: 94 · 2017: 78 · 2016: 96 · 2015: 65 · 2014: 16
FWCI
66.80
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • ResearchSpace (University of Auckland) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • Amgen
  • National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc085083-027, n01hc085080-026, n01hc095169-003, n01hc085086-022, UL1TR001079, n01hc25195-41-0-1, n01hc55222-0-0-0, n01hc95159-40-0-1)
  • Medical Research Council (MC_PC_13040, MR/K007017/1)
  • National Institute on Aging (R01AG007181, R01AG023629, R01AG028507)
  • National Heart, Lung, and Blood Institute (HHSN268201 100012C, N01 HC085086, HHSN268201100007C, N01-HC095169, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, N01 HC085079, N01 HC085083, N01 HC085080, HHSN268201100005C, R01HL068140, HHSN 268200800007C, HHSN268201100010C, N01-HC-095159, N01-HC-025195, HHSN268201200036C, HHSN26820 1100009C, N01HC085082, N01 HC055222, R01HL043232, N01 HC085081, R01HL080295)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K23DK067303, R01DK031801, K23DK002904, U01DK035073, R01DK100446)
  • National Center for Research Resources (UL1RR024156, UL1RR025005)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Keywords
chronic kidney disease progression, estimated glomerular filtration rate decline, end-stage renal disease, all-cause mortality, serum creatinine, dialysis initiation, kidney transplantation, albuminuria, diabetes mellitus, individual patient data meta-analysis, cohort studies, random-effects meta-analysis, hazard ratio
MeSH terms
Adult, Aged, Aged, 80 and over, Creatinine, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Reference Values, Risk, Cohort Studies, Disease Progression, Endpoint Determination

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