• Tamara Isakova, Xuan Cai, Jungwha Lee, Rupal Mehta, Xiaoming Zhang, Wei Yang, Lisa Nessel, Amanda Hyre Anderson, Joan Lo, Anna Porter, Julie Wright Nunes, Lavinia Negrea, Lee Hamm, Edward Horwitz, Jing Chen, Julia J Scialla, Ian H de Boer, Mary B Leonard, Harold I Feldman, Myles Wolf, and CRIC Study Investigators.
• Division of Nephrology and Hypertension, Department of Medicine, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL; Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address: tamara.isakova@northwestern.edu.
• Am. J. Kidney Dis. 2020 Feb 1; 75 (2): 235-244.

Rationale & ObjectiveThe pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD.Study DesignRetrospective analysis nested in a cohort study.Setting & ParticipantsParticipants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847).ExposureYears before ESKD.OutcomesSerial FGF-23, PTH, serum phosphate, and serum calcium levels.Analytical ApproachTo assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD.ResultsMean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased.LimitationsIndividuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied.ConclusionsAmong patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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