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 journalArticle

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)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2019

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Chronic Renal Insufficiency
Chronic Kidney Failure
Minerals
Cohort Studies
Parathyroid Hormone
Deceleration
Phosphates
Serum
Glomerular Filtration Rate
Vitamin D
Longitudinal Studies
Disease Progression
Retrospective Studies
Cross-Sectional Studies
fibroblast growth factor 23
Calcium

Keywords

  • biomarker
  • calcium
  • Chronic kidney disease (CKD)
  • CKD progression
  • 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

Cite this

@article{4ea6d3fd01344ab89d67af2230fe3f33,
title = "Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study",
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.",
keywords = "biomarker, calcium, Chronic kidney disease (CKD), CKD progression, 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",
author = "{CRIC Study Investigators} and Tamara Isakova and Xuan Cai and Jungwha Lee and Rupal Mehta and Xiaoming Zhang and Wei Yang and Lisa Nessel and Anderson, {Amanda Hyre} and Joan Lo and Anna Porter and Nunes, {Julie Wright} and Lavinia Negrea and Lee Hamm and Edward Horwitz and Jing Chen and Scialla, {Julia J.} and {de Boer}, {Ian H.} and Leonard, {Mary B.} and Feldman, {Harold I.} and Myles Wolf and Appel, {Lawrence J.} and Go, {Alan S.} and Jiang He and Lash, {James P.} and Akinlolu Ojo and Mahboob Rahman and Townsend, {Raymond R.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2019.07.022",
language = "English (US)",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD

T2 - The Chronic Renal Insufficiency Cohort (CRIC) Study

AU - CRIC Study Investigators

AU - Isakova, Tamara

AU - Cai, Xuan

AU - Lee, Jungwha

AU - Mehta, Rupal

AU - Zhang, Xiaoming

AU - Yang, Wei

AU - Nessel, Lisa

AU - Anderson, Amanda Hyre

AU - Lo, Joan

AU - Porter, Anna

AU - Nunes, Julie Wright

AU - Negrea, Lavinia

AU - Hamm, Lee

AU - Horwitz, Edward

AU - Chen, Jing

AU - Scialla, Julia J.

AU - de Boer, Ian H.

AU - Leonard, Mary B.

AU - Feldman, Harold I.

AU - Wolf, Myles

AU - Appel, Lawrence J.

AU - Go, Alan S.

AU - He, Jiang

AU - Lash, James P.

AU - Ojo, Akinlolu

AU - Rahman, Mahboob

AU - Townsend, Raymond R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - biomarker

KW - calcium

KW - Chronic kidney disease (CKD)

KW - CKD progression

KW - disordered mineral metabolism

KW - end-stage renal disease (ESRD)

KW - fibroblast growth factor 23 (FGF-23)

KW - incident kidney failure

KW - kidney function

KW - longitudinal trends

KW - parathyroid hormone (PTH)

KW - phosphate

KW - serial measurements

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UR - http://www.scopus.com/inward/citedby.url?scp=85074322716&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2019.07.022

DO - 10.1053/j.ajkd.2019.07.022

M3 - Article

C2 - 31668375

AN - SCOPUS:85074322716

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

ER -