Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

CRIC Study Investigators

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale & Objective: The 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 Design: Retrospective analysis nested in a cohort study. Setting & Participants: Participants 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). Exposure: Years before ESKD. Outcomes: Serial FGF-23, PTH, serum phosphate, and serum calcium levels. Analytical Approach: To 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. Results: Mean 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. Limitations: Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Conclusions: Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume75
Issue number2
DOIs
StatePublished - Feb 2020

Keywords

  • CKD progression
  • Chronic kidney disease (CKD)
  • biomarker
  • calcium
  • disordered mineral metabolism
  • end-stage renal disease (ESRD)
  • fibroblast growth factor 23 (FGF-23)
  • incident kidney failure
  • kidney function
  • longitudinal trends
  • parathyroid hormone (PTH)
  • phosphate
  • serial measurements

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study'. Together they form a unique fingerprint.

Cite this