Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease

Michel Chonchol, Berenice Gitomer, Tamara Isakova, Xuan Cai, Isidro Salusky, Renata Pereira, Kaleab Abebe, Vicente Torres, Theodor I. Steinman, Jared J. Grantham, Arlene B. Chapman, Robert W. Schrier, Myles Wolf

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and objectives Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. Design, setting, participants & measurements We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in theHALT-PKD Study A (n=540;mean eGFR =91617ml/min per 1.73m2) and B (n=462; mean eGFR =48612 ml/min per 1.73 m2). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in heightadjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Results Median (interquartile range) intact fibroblast growth factor 23 was 44 (33–56) pg/ml in HALT-PKD Study A and 69 (50–93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, 23.62; 95% confidence interval, 24.12 to 23.12 versus quartile 1, 22.51; 95% confidence interval, 22.71 to 22.30 ml/min per 1.73 m2; P for trend <0.001; Study B: quartile 4, 23.74; 95% confidence interval, 24.14 to 23.34 versus quartile 1, 22.78; 95% confidence interval, 22.92 to 22.63 ml/min per 1.73 m2; P for trend, <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m2 did not improve risk prediction. Conclusions Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.

Original languageEnglish (US)
Pages (from-to)1461-1469
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number9
DOIs
StatePublished - Sep 7 2017

Fingerprint

Autosomal Dominant Polycystic Kidney
Kidney Diseases
Disease Progression
Confidence Intervals
Kidney
fibroblast growth factor 23
Serum
Proportional Hazards Models
Chronic Kidney Failure

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease. / Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I.; Grantham, Jared J.; Chapman, Arlene B.; Schrier, Robert W.; Wolf, Myles.

In: Clinical Journal of the American Society of Nephrology, Vol. 12, No. 9, 07.09.2017, p. 1461-1469.

Research output: Contribution to journalArticle

Chonchol, M, Gitomer, B, Isakova, T, Cai, X, Salusky, I, Pereira, R, Abebe, K, Torres, V, Steinman, TI, Grantham, JJ, Chapman, AB, Schrier, RW & Wolf, M 2017, 'Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease', Clinical Journal of the American Society of Nephrology, vol. 12, no. 9, pp. 1461-1469. https://doi.org/10.2215/CJN.12821216
Chonchol, Michel ; Gitomer, Berenice ; Isakova, Tamara ; Cai, Xuan ; Salusky, Isidro ; Pereira, Renata ; Abebe, Kaleab ; Torres, Vicente ; Steinman, Theodor I. ; Grantham, Jared J. ; Chapman, Arlene B. ; Schrier, Robert W. ; Wolf, Myles. / Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease. In: Clinical Journal of the American Society of Nephrology. 2017 ; Vol. 12, No. 9. pp. 1461-1469.
@article{bd36c2dcfff2425ba2bead190ea2f6d1,
title = "Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease",
abstract = "Background and objectives Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. Design, setting, participants & measurements We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in theHALT-PKD Study A (n=540;mean eGFR =91617ml/min per 1.73m2) and B (n=462; mean eGFR =48612 ml/min per 1.73 m2). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in heightadjusted total kidney volume, and composite of time to 50{\%} reduction in eGFR, onset of ESRD, or death. Results Median (interquartile range) intact fibroblast growth factor 23 was 44 (33–56) pg/ml in HALT-PKD Study A and 69 (50–93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, 23.62; 95{\%} confidence interval, 24.12 to 23.12 versus quartile 1, 22.51; 95{\%} confidence interval, 22.71 to 22.30 ml/min per 1.73 m2; P for trend <0.001; Study B: quartile 4, 23.74; 95{\%} confidence interval, 24.14 to 23.34 versus quartile 1, 22.78; 95{\%} confidence interval, 22.92 to 22.63 ml/min per 1.73 m2; P for trend, <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95{\%} confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95{\%} confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95{\%} confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m2 did not improve risk prediction. Conclusions Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.",
author = "Michel Chonchol and Berenice Gitomer and Tamara Isakova and Xuan Cai and Isidro Salusky and Renata Pereira and Kaleab Abebe and Vicente Torres and Steinman, {Theodor I.} and Grantham, {Jared J.} and Chapman, {Arlene B.} and Schrier, {Robert W.} and Myles Wolf",
year = "2017",
month = "9",
day = "7",
doi = "10.2215/CJN.12821216",
language = "English (US)",
volume = "12",
pages = "1461--1469",
journal = "Clinical Journal of the American Society of Nephrology",
issn = "1555-9041",
publisher = "American Society of Nephrology",
number = "9",

}

TY - JOUR

T1 - Fibroblast growth factor 23 and kidney disease progression in autosomal dominant polycystic kidney disease

AU - Chonchol, Michel

AU - Gitomer, Berenice

AU - Isakova, Tamara

AU - Cai, Xuan

AU - Salusky, Isidro

AU - Pereira, Renata

AU - Abebe, Kaleab

AU - Torres, Vicente

AU - Steinman, Theodor I.

AU - Grantham, Jared J.

AU - Chapman, Arlene B.

AU - Schrier, Robert W.

AU - Wolf, Myles

PY - 2017/9/7

Y1 - 2017/9/7

N2 - Background and objectives Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. Design, setting, participants & measurements We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in theHALT-PKD Study A (n=540;mean eGFR =91617ml/min per 1.73m2) and B (n=462; mean eGFR =48612 ml/min per 1.73 m2). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in heightadjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Results Median (interquartile range) intact fibroblast growth factor 23 was 44 (33–56) pg/ml in HALT-PKD Study A and 69 (50–93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, 23.62; 95% confidence interval, 24.12 to 23.12 versus quartile 1, 22.51; 95% confidence interval, 22.71 to 22.30 ml/min per 1.73 m2; P for trend <0.001; Study B: quartile 4, 23.74; 95% confidence interval, 24.14 to 23.34 versus quartile 1, 22.78; 95% confidence interval, 22.92 to 22.63 ml/min per 1.73 m2; P for trend, <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m2 did not improve risk prediction. Conclusions Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.

AB - Background and objectives Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. Design, setting, participants & measurements We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in theHALT-PKD Study A (n=540;mean eGFR =91617ml/min per 1.73m2) and B (n=462; mean eGFR =48612 ml/min per 1.73 m2). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in heightadjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Results Median (interquartile range) intact fibroblast growth factor 23 was 44 (33–56) pg/ml in HALT-PKD Study A and 69 (50–93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, 23.62; 95% confidence interval, 24.12 to 23.12 versus quartile 1, 22.51; 95% confidence interval, 22.71 to 22.30 ml/min per 1.73 m2; P for trend <0.001; Study B: quartile 4, 23.74; 95% confidence interval, 24.14 to 23.34 versus quartile 1, 22.78; 95% confidence interval, 22.92 to 22.63 ml/min per 1.73 m2; P for trend, <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m2 did not improve risk prediction. Conclusions Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.

UR - http://www.scopus.com/inward/record.url?scp=85029601874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029601874&partnerID=8YFLogxK

U2 - 10.2215/CJN.12821216

DO - 10.2215/CJN.12821216

M3 - Article

C2 - 28705885

AN - SCOPUS:85029601874

VL - 12

SP - 1461

EP - 1469

JO - Clinical Journal of the American Society of Nephrology

JF - Clinical Journal of the American Society of Nephrology

SN - 1555-9041

IS - 9

ER -