Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets.

BACKGROUND

Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. "CKD Patch" is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.

METHODS

Utilizing data from 4,143,535 adults from 35 datasets, we developed several "CKD Patches" incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch.

FINDINGS

We confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018-0.036] and 0.010 [0.007-0.013] and categorical net reclassification improvement 0.080 [0.032-0.127] and 0.056 [0.044-0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89-3.40) in very high-risk CKD (e.g., eGFR 30-44 ml/min/1.73m

INTERPRETATION

The "CKD Patch" can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available.

FUNDING

US National Kidney Foundation and the NIDDK.

Informations de copyright

© 2020 The Authors.

Déclaration de conflit d'intérêts

Dr. Matsushita reports grants from NIH during the conduct of the study; grants and personal fees from Kyowa Kirin and personal fees from Akebia outside the submitted work. Dr. Grams reports grants from NKF and grants from NIH during the conduct of the study and received travel funds to speak at DCI Director's meeting. Dr. Ärnlöv reports personal fees from AstraZeneca outside the submitted work. Dr. Ebert reports personal fees from Bayer AG, personal fees from Siemens Healthineers, and personal fees from Roche Diagnostics outside the submitted work. Dr. Eckardt reports grants from Astra Zeneca, grants from Bayer, grants from FMC, and grants from Vifor during the conduct of the study; personal fees from Akebia, personal fees from Astellas, personal fees from Bayer, and personal fees from Vifor outside the submitted work. Dr. Gutierrez reports grants and personal fees from Akebia, grants and personal fees from Amgen, grants from GSK, personal fees from QED, grants from National Institutes of Health, and grants from American Heart Association outside the submitted work. Dr. Kovesdy reports personal fees from Amgen, personal fees from Sanofi-Aventis, personal fees from Fresenius Medical Care, personal fees from Keryx, grants from Shire, personal fees from Bayer, personal fees from Abbott, personal fees from Abbvie, personal fees from Dr. Schar, personal fees from Astra-Zeneca, personal fees from Takeda, personal fees from Tricida, and personal fees from Reata outside the submitted work. Dr. Levey reports grants from NIDDK during the conduct of the study. Dr. Lloyd-Jones reports grants from NIH during the conduct of the study. Dr. Muntner reports grant support and consulting fees unrelated to this project. Dr. Nadkarni reports grants, personal fees, non-financial support and other from Renalytix AI, non-financial support and other from Pensieve Health, personal fees from Reata, personal fees from AstraZeneca, and personal fees from GLG Consulting outside the submitted work. Dr. Ohkubo reports grants from Omron Healthcare Co. Ltd. outside the submitted work. Dr. Shlipak reports consultancy fees from Cricket Health and Intercept Pharmaceuticals and stocks/stock options from TAI Diagnostics where he is a Scientific Advisor outside the submitted work. Dr. Woodward reports personal fees from Amgen and personal fees from Kirin outside the submitted work. Dr. Zhang reports grants from National Natural Science Foundation of China, grants from Beijing Nova Program Interdisciplinary Cooperation Project, grants from University of Michigan Health System-Peking University Health Science Center Joint Institute for Translational and Clinical Research, grants from PKU-Baidu Fund, grants from Peking University, and grants from AstraZeneca during the conduct of the study. Dr. Schaeffner reports other from Siemens Healthineers, other support from Fresenius Kabi and other support from Fresenius Medical Care outside the submitted work. Dr. Coresh reports grants from NIH and grants from National Kidney Foundation during the conduct of the study; personal fees and other support from Healthy.io outside the submitted work. All other coauthors have nothing to disclose.