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

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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Figure 1

Fully adjusted splines of estimated glomerular filtration rate (eGFR) against adjusted hazard ratio (with 95% confidence limits) for all-cause mortality (top row), composite fatal/non-fatal cardiovascular disease (CVD) (second row) and fatal CVD (third row) using eGFR based on creatinine (eGFRcr; left column), eGFR based on cystatin C (eGFRcys; middle column) and eGFR based on creatinine and cystatin C (eGFRcr-cys; right column).

Figure 2

Heat maps for prediction of all-cause mortality, composite fatal/non-fatal cardiovascular disease (CVD), fatal CVD and end-stage kidney disease using eGFRcys and albuminuria (urine albumin:creatinine ratio; uACR) for estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcr; top), eGFR based on cystatin C (eGFRcys; middle) and eGFR based on creatinine and cystatin C (eGFRcr-cys; bottom). No data were available for those with eGFR >90ml/min/1.73m² and uACR >3mg/mmol. Otherwise, hazard ratios adjusted for atherosclerotic risk factors (age, sex, ethnicity, systolic and diastolic blood pressure, antihypertensive medications, statin use, smoking, diabetes, total and high-density lipoprotein cholesterol) were ranked 1-13 (1 being the lowest risk), and heat maps were colour-coded for all outcomes: 1-4 (green), 5-7 (yellow), 8-10 (orange), 11-13 (red).

Figure 3

Change in C-statistic with 95% confidence intervals for composite fatal/non-fatal cardiovascular disease, fatal cardiovascular disease or all-cause mortality upon addition of each estimated glomerular filtration rate (eGFR) method: eGFR based on creatinine (eGFRcr), eGFR based on cystatin C (eGFRcys) and eGFR based on creatinine and cystatin C (eGFRcr-cys). The centre line (0.00) represents no change to C-index.