TY - JOUR
T1 - Changes in GFR and Albuminuria in Routine Clinical Practice and the Risk of Kidney Disease Progression
AU - Neuen, Brendon L.
AU - Weldegiorgis, Misghina
AU - Herrington, William G.
AU - Ohkuma, Toshiaki
AU - Smith, Margaret
AU - Woodward, Mark
N1 - Funding Information:
This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford. B.L. Neuen is supported by an Oxford Australia Clarendon Scholarship, the Graduate Research Fund at Lincoln College, University of Oxford, an Australian National Health and Medical Research Council Postgraduate Scholarship and a University Postgraduate Award from University of New South Wales Sydney. W.G. Herrington is supported by a Medical Research Council and Kidney Research UK Professor David Kerr Clinician Scientist Award. M. Smith is supported by the NIHR Biomedical Research Centre, Oxford. The funders had no role in study design, data collection, analysis, reporting, or the decision to submit for publication.
Funding Information:
Brendon L. Neuen, MBBS(Hons), MSc, Misghina Weldegiorgis, PhD, William G. Herrington, MBBS, MD, Toshiaki Ohkuma, MD, PhD, Margaret Smith, PhD, and Mark Woodward, PhD. Research idea and study design: BLN, WGH, TO, MWoodward; data acquisition: MWeldegiorgis, MS, WGH, MWoodward; data analysis/interpretation: BLN, MWeldegiorgis, WGH, MS, TO, MWoodward; statistical analysis: BLN, MWeldegiorgis, MS; supervision and mentorship: MWeldegiorgis, WGH, MWoodward. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford. B.L. Neuen is supported by an Oxford Australia Clarendon Scholarship, the Graduate Research Fund at Lincoln College, University of Oxford, an Australian National Health and Medical Research Council Postgraduate Scholarship and a University Postgraduate Award from University of New South Wales Sydney. W.G. Herrington is supported by a Medical Research Council and Kidney Research UK Professor David Kerr Clinician Scientist Award. M. Smith is supported by the NIHR Biomedical Research Centre, Oxford. The funders had no role in study design, data collection, analysis, reporting, or the decision to submit for publication. Dr Neuen has received travel support from Janssen and consultancy fees from Bayer. Mr Woodward reports personal fees from Amgen and Kirin outside the submitted work. All other authors declare that they have no relevant financial interests. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. Clinical Practice Research Datalink data are open access. Information on how to access the data used for these analyses is available at https://www.cprd.com/home. Aspects of this work were presented at the 55th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology (ANZSN), November 28 to December 2, 2020. Received July 11, 2020. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form February 14, 2021.
Publisher Copyright:
© 2021 National Kidney Foundation, Inc.
PY - 2021/9
Y1 - 2021/9
N2 - Rationale & Objective: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. Study Design: Observational cohort study. Setting & Participants: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. Exposures: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. Outcomes: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. Analytical Approach: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. Results: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. Limitations: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. Conclusions: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.
AB - Rationale & Objective: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. Study Design: Observational cohort study. Setting & Participants: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. Exposures: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. Outcomes: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. Analytical Approach: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. Results: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. Limitations: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. Conclusions: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.
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U2 - 10.1053/j.ajkd.2021.02.335
DO - 10.1053/j.ajkd.2021.02.335
M3 - Article
C2 - 33895181
AN - SCOPUS:85107071420
SN - 0272-6386
VL - 78
SP - 350-360.e1
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -
