Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease

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Abstract

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.

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Fig. 1: Fully adjusted splines of estimated GFR (eGFR) against adjusted hazard ratio (with 95% confidence limits).
Fig. 2: Heat maps for prediction of all-cause mortality, composite fatal/nonfatal CVD, fatal CVD and ESKD.
Fig. 3: Change in C-statistic with 95% CI for composite fatal/nonfatal CVD, fatal CVD or all-cause mortality.

Data availability

The UK Biobank data that support the findings of this study are available from the UK Biobank (www.ukbiobank.ac.uk). This study was conducted under project code 9310.

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Acknowledgements

We thank the participants of the UK Biobank. The work in this study was supported by a grant from Chest, Heart and Stroke Association Scotland (grant no. Res16/A165). J.S.L. has personal funding from a Kidney Research UK Training Fellowship Award (no. TF_013_20161125) and is supported by a British Heart Foundation Centre of Excellence Award (no. RE/13/5/30177).

Author information

J.S.L. and P.B.M. conceived of and designed the study. Data were analyzed by C.E.W. and P.W. under UK Biobank project 9310 led by N.S. and involving all authors. The first draft of the manuscript was written by J.S.L. and C.E.W. All authors (J.S.L., C.E.W., P.W., P.B.M., N.S., C.A.C-M., D.M., S.R.G., J.G.C., J.M.R.G., P.S.J., J.L., D.M.L., J.P.) read, critically revised and approved the final manuscript.

Correspondence to Jennifer S. Lees.

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The authors declare no competing interests.

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Peer review information Jennifer Sargent was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Extended data

Extended Data Fig. 1 Unadjusted survival of effects of eGFRcr category on all-cause mortality.

Unadjusted survival of effects of eGFRcr category on all-cause mortality. Event-free survival decreases as eGFRcr declines.

Extended Data Fig. 2 Unadjusted survival plot of effects of eGFRcr category on composite fatal/non-fatal cardiovascular disease.

Unadjusted survival plot of effects of eGFRcr category on composite fatal/non-fatal cardiovascular disease. Event-free survival decreases as eGFRcr declines.

Extended Data Fig. 3 Unadjusted survival plot of effects of eGFRcr category on fatal cardiovascular disease.

Unadjusted survival plot of effects of eGFRcr category on fatal cardiovascular disease. Event-free survival decreases as eGFRcr declines.

Extended Data Fig. 4 Unadjusted survival plot of effects of eGFRcr category on end-stage kidney disease.

Unadjusted survival plot of effects of eGFRcr category on end-stage kidney disease. Event-free survival decreases as eGFRcr declines, particularly in those with CKLD3b/4 (eGFRcr 15–45 ml/min/1.73 m2) at baseline.

Extended Data Fig. 5 Fully adjusted splines of eGFR and hazard ratio for end-stage kidney disease.

Fully adjusted splines of eGFR and hazard ratio for end-stage kidney disease using eGFRcr (left column), eGFRcys (middle column) and eGFRcr-cys (right column).

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Lees, J.S., Welsh, C.E., Celis-Morales, C.A. et al. Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med 25, 1753–1760 (2019) doi:10.1038/s41591-019-0627-8

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