Risk of ESRD and Mortality Associated With Change in Filtration Markers

Casey M. Rebholz; Lesley A. Inker; Yuan Chen; Menglu Liang; Meredith C. Foster; John H. Eckfeldt; Paul L. Kimmel; Ramachandran S. Vasan; Harold I. Feldman; Mark J. Sarnak; Chi yuan Hsu; Andrew S. Levey; Josef Coresh

doi:10.1053/j.ajkd.2017.04.025

Risk of ESRD and Mortality Associated With Change in Filtration Markers

Casey M. Rebholz
, Lesley A. Inker
, Yuan Chen
, Menglu Liang
, Meredith C. Foster
, John H. Eckfeldt
, Paul L. Kimmel
, Ramachandran S. Vasan
, Harold I. Feldman
, Mark J. Sarnak
, Chi yuan Hsu
, Andrew S. Levey
, Josef Coresh

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of 2 clinical trials. Setting & Participants Participants in the MDRD (Modification of Diet in Renal Disease; n = 317) Study and AASK (African American Study of Kidney Disease and Hypertension; n = 373). Predictors Creatinine, cystatin C, β-trace protein (BTP), and β₂-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality. Measurements Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. Results 1-year decline in mGFR, eGFR_cr, eGFR_BTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P ≤ 0.02). Compared to mGFR, only decline in eGFR_BTP was statistically significantly more strongly associated with ESRD risk in both studies (both P ≤ 0.03). Decline in eGFR_cr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P < 0.001), but this association was not significantly different from decline in mGFR (P = 0.2). Limitations Small sample size. Conclusions Declines in mGFR, eGFR_cr, eGFR_BTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

Original language	English (US)
Pages (from-to)	551-560
Number of pages	10
Journal	American Journal of Kidney Diseases
Volume	70
Issue number	4
DOIs	https://doi.org/10.1053/j.ajkd.2017.04.025
State	Published - Oct 2017

Bibliographical note

Publisher Copyright:
© 2017 National Kidney Foundation, Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Beta-2-microglobulin (B2M)
beta trace protein (BTP)
creatinine
cystatin C
death
end-stage renal disease (ESRD)
estimated GFR
filtration markers
glomerular filtration rate (GFR)
incident ESRD
kidney function decline
measured GFR
mortality

Publisher link

10.1053/j.ajkd.2017.04.025

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610931

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@article{342bdb48e1134533b81e855f8902bf09,

title = "Risk of ESRD and Mortality Associated With Change in Filtration Markers",

abstract = "Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of 2 clinical trials. Setting \& Participants Participants in the MDRD (Modification of Diet in Renal Disease; n = 317) Study and AASK (African American Study of Kidney Disease and Hypertension; n = 373). Predictors Creatinine, cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality. Measurements Poisson regression was used to estimate incidence rate ratios and 95\% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30\% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. Results 1-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P ≤ 0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both P ≤ 0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30\% decline, 4.17; 95\% CI, 1.78-9.74; P < 0.001), but this association was not significantly different from decline in mGFR (P = 0.2). Limitations Small sample size. Conclusions Declines in mGFR, eGFRcr, eGFRBTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.",

keywords = "Beta-2-microglobulin (B2M), beta trace protein (BTP), creatinine, cystatin C, death, end-stage renal disease (ESRD), estimated GFR, filtration markers, glomerular filtration rate (GFR), incident ESRD, kidney function decline, measured GFR, mortality",

author = "Rebholz, \{Casey M.\} and Inker, \{Lesley A.\} and Yuan Chen and Menglu Liang and Foster, \{Meredith C.\} and Eckfeldt, \{John H.\} and Kimmel, \{Paul L.\} and Vasan, \{Ramachandran S.\} and Feldman, \{Harold I.\} and Sarnak, \{Mark J.\} and Hsu, \{Chi yuan\} and Levey, \{Andrew S.\} and Josef Coresh",

note = "Publisher Copyright: {\textcopyright} 2017 National Kidney Foundation, Inc.",

year = "2017",

month = oct,

doi = "10.1053/j.ajkd.2017.04.025",

language = "English (US)",

volume = "70",

pages = "551--560",

journal = "American Journal of Kidney Diseases",

issn = "0272-6386",

publisher = "W.B. Saunders",

number = "4",

}

TY - JOUR

T1 - Risk of ESRD and Mortality Associated With Change in Filtration Markers

AU - Rebholz, Casey M.

AU - Inker, Lesley A.

AU - Chen, Yuan

AU - Liang, Menglu

AU - Foster, Meredith C.

AU - Eckfeldt, John H.

AU - Kimmel, Paul L.

AU - Vasan, Ramachandran S.

AU - Feldman, Harold I.

AU - Sarnak, Mark J.

AU - Hsu, Chi yuan

AU - Levey, Andrew S.

AU - Coresh, Josef

PY - 2017/10

Y1 - 2017/10

N2 - Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of 2 clinical trials. Setting & Participants Participants in the MDRD (Modification of Diet in Renal Disease; n = 317) Study and AASK (African American Study of Kidney Disease and Hypertension; n = 373). Predictors Creatinine, cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality. Measurements Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. Results 1-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P ≤ 0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both P ≤ 0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P < 0.001), but this association was not significantly different from decline in mGFR (P = 0.2). Limitations Small sample size. Conclusions Declines in mGFR, eGFRcr, eGFRBTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

AB - Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of 2 clinical trials. Setting & Participants Participants in the MDRD (Modification of Diet in Renal Disease; n = 317) Study and AASK (African American Study of Kidney Disease and Hypertension; n = 373). Predictors Creatinine, cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality. Measurements Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. Results 1-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P ≤ 0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both P ≤ 0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P < 0.001), but this association was not significantly different from decline in mGFR (P = 0.2). Limitations Small sample size. Conclusions Declines in mGFR, eGFRcr, eGFRBTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

KW - Beta-2-microglobulin (B2M)

KW - beta trace protein (BTP)

KW - creatinine

KW - cystatin C

KW - death

KW - end-stage renal disease (ESRD)

KW - estimated GFR

KW - filtration markers

KW - glomerular filtration rate (GFR)

KW - incident ESRD

KW - kidney function decline

KW - measured GFR

KW - mortality

UR - https://www.scopus.com/pages/publications/85021088339

UR - https://www.scopus.com/pages/publications/85021088339#tab=citedBy

U2 - 10.1053/j.ajkd.2017.04.025

DO - 10.1053/j.ajkd.2017.04.025

M3 - Article

C2 - 28648303

AN - SCOPUS:85021088339

SN - 0272-6386

VL - 70

SP - 551

EP - 560

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

IS - 4

ER -

Risk of ESRD and Mortality Associated With Change in Filtration Markers

Abstract

Bibliographical note

UN SDGs

Keywords

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