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Changes in GFR and Albuminuria in Routine Clinical Practice and the Risk of Kidney Disease Progression

  • Brendon L. Neuen
    Correspondence
    Address for Correspondence: Brendon L. Neuen, MBBS(Hons), MSc, The George Institute for Global Health, University of New South Wales, Level 5, 1 King St, Newtown 2042, NSW, Australia.
    Affiliations
    George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia
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  • Misghina Weldegiorgis
    Affiliations
    George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia

    Department of Epidemiology and Biostatistics, School of Public Health, The George Institute for Global Health, Imperial College London, London
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  • William G. Herrington
    Affiliations
    Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, United Kingdom
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  • Toshiaki Ohkuma
    Affiliations
    George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia

    Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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  • Margaret Smith
    Affiliations
    Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom

    National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
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  • Mark Woodward
    Affiliations
    George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia

    Department of Epidemiology and Biostatistics, School of Public Health, The George Institute for Global Health, Imperial College London, London

    Department of Epidemiology, John Hopkins University, Baltimore, MD
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Published:April 22, 2021DOI:https://doi.org/10.1053/j.ajkd.2021.02.335

      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.

      Graphical abstract

      Index Words

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