Risk of ESRD and Mortality Associated With Change in Filtration Markers

Casey 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Dec 18 2016

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Chronic Kidney Failure
Mortality
Cystatin C
Creatinine
Glomerular Filtration Rate
Chronic Renal Insufficiency
Clinical Trials
Diet Therapy
Incidence
Kidney Diseases
African Americans
Sample Size
Observational Studies
Hypertension
Kidney
Serum
Population
Proteins

Keywords

  • Beta trace protein (BTP)
  • Beta-2-microglobulin (B2M)
  • 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

ASJC Scopus subject areas

  • Nephrology

Cite this

Risk of ESRD and Mortality Associated With Change in Filtration Markers. / Rebholz, Casey; Inker, Lesley A.; Chen, Yuan; Liang, Menglu; Foster, Meredith C.; Eckfeldt, John H.; Kimmel, Paul L.; Vasan, Ramachandran S.; Feldman, Harold I.; Sarnak, Mark J.; Hsu, Chi yuan; Levey, Andrew S.; Coresh, Josef.

In: American Journal of Kidney Diseases, 18.12.2016.

Research output: Contribution to journalArticle

Rebholz, C, Inker, LA, Chen, Y, Liang, M, Foster, MC, Eckfeldt, JH, Kimmel, PL, Vasan, RS, Feldman, HI, Sarnak, MJ, Hsu, CY, Levey, AS & Coresh, J 2016, 'Risk of ESRD and Mortality Associated With Change in Filtration Markers', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2017.04.025
Rebholz, Casey ; Inker, Lesley A. ; Chen, Yuan ; Liang, Menglu ; Foster, Meredith C. ; Eckfeldt, John H. ; Kimmel, Paul L. ; Vasan, Ramachandran S. ; Feldman, Harold I. ; Sarnak, Mark J. ; Hsu, Chi yuan ; Levey, Andrew S. ; Coresh, Josef. / Risk of ESRD and Mortality Associated With Change in Filtration Markers. In: American Journal of Kidney Diseases. 2016.
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keywords = "Beta trace protein (BTP), Beta-2-microglobulin (B2M), 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",
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T1 - Risk of ESRD and Mortality Associated With Change in Filtration Markers

AU - Rebholz, Casey

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 - 2016/12/18

Y1 - 2016/12/18

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 trace protein (BTP)

KW - Beta-2-microglobulin (B2M)

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

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