TY - JOUR
T1 - Change in novel filtration markers and risk of ESRD
AU - Rebholz, Casey M.
AU - Grams, Morgan E.
AU - Matsushita, Kunihiro
AU - Selvin, Elizabeth
AU - Coresh, Josef
N1 - Funding Information:
Support: The ARC Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute (NHLBI) contracts ( HHSN268201100005C , HHSN268201100006C , HHSN268201100007C , HHSN268201100008C , HHSN268201100009C , HHSN268201100010C , HHSN268201100011C , and HHSN268201100012C ).
Funding Information:
Additional support was provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01 DK076770 (Principal Investigator: B. Astor/L. Kao) and R01 DK089174 (Principal Investigator: E. Selvin). Dr Rebholz is supported in part by NHLBI grant T32 HL007024 . Dr Coresh is partially supported by NIDDK grant U01 DK085689 (CKD Biomarkers Consortium).
Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Background Chronic kidney disease progression is a risk factor for end-stage renal disease (ESRD). A 57% decline in creatinine-based estimated glomerular filtration rate (eGFRcr) is an established surrogate outcome for ESRD in clinical trials, and a 30% decrease recently has been proposed as a surrogate end point. However, it is unclear whether change in novel filtration marker levels provides additional information for ESRD risk to change in eGFRcr. Study Design Cohort study. Setting & Participants Atherosclerosis Risk in Communities (ARIC) Study participants from 4 US communities. Predictors Percent change in levels of filtration markers (eGFRcr, cystatin C-based eGFR [eGFRcys], the inverse of β2-microglobulin concentration [1/B2M]) over a 6-year period. Outcome Incident ESRD. Measurements Cox proportional hazards regression with adjustment for demographics, kidney disease risk factors, and first measurement of eGFRcr. Results During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFRcr, eGFRcys, and 1/B2M were associated significantly with ESRD compared with stable concentrations of filtration markers (HRs of 19.96 [95% CI, 11.73-33.96], 16.67 [95% CI, 10.27-27.06], and 22.53 [95% CI, 13.20-38.43], respectively). Using the average of declines in the 3 markers, >30% decline conferred higher ESRD risk than that for eGFRcr alone (HR, 31.97 [95% CI, 19.40-52.70; P = 0.03] vs eGFRcr). Limitations Measurement error could influence estimation of change in filtration marker levels. Conclusions A >30% decline in kidney function assessed using novel filtration markers is associated strongly with ESRD, suggesting the potential utility of measuring change in cystatin C and B2M levels in settings in which improved outcome ascertainment is needed, such as clinical trials.
AB - Background Chronic kidney disease progression is a risk factor for end-stage renal disease (ESRD). A 57% decline in creatinine-based estimated glomerular filtration rate (eGFRcr) is an established surrogate outcome for ESRD in clinical trials, and a 30% decrease recently has been proposed as a surrogate end point. However, it is unclear whether change in novel filtration marker levels provides additional information for ESRD risk to change in eGFRcr. Study Design Cohort study. Setting & Participants Atherosclerosis Risk in Communities (ARIC) Study participants from 4 US communities. Predictors Percent change in levels of filtration markers (eGFRcr, cystatin C-based eGFR [eGFRcys], the inverse of β2-microglobulin concentration [1/B2M]) over a 6-year period. Outcome Incident ESRD. Measurements Cox proportional hazards regression with adjustment for demographics, kidney disease risk factors, and first measurement of eGFRcr. Results During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFRcr, eGFRcys, and 1/B2M were associated significantly with ESRD compared with stable concentrations of filtration markers (HRs of 19.96 [95% CI, 11.73-33.96], 16.67 [95% CI, 10.27-27.06], and 22.53 [95% CI, 13.20-38.43], respectively). Using the average of declines in the 3 markers, >30% decline conferred higher ESRD risk than that for eGFRcr alone (HR, 31.97 [95% CI, 19.40-52.70; P = 0.03] vs eGFRcr). Limitations Measurement error could influence estimation of change in filtration marker levels. Conclusions A >30% decline in kidney function assessed using novel filtration markers is associated strongly with ESRD, suggesting the potential utility of measuring change in cystatin C and B2M levels in settings in which improved outcome ascertainment is needed, such as clinical trials.
KW - chronic kidney disease (CKD)
KW - creatinine
KW - cystatin C
KW - disease progression
KW - end-stage renal disease (ESRD)
KW - filtration marker
KW - kidney disease outcome
KW - surrogate endpoint
KW - β-Microglobulin (B2M)
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U2 - 10.1053/j.ajkd.2014.11.009
DO - 10.1053/j.ajkd.2014.11.009
M3 - Article
C2 - 25542414
AN - SCOPUS:84937428111
SN - 0272-6386
VL - 66
SP - 47
EP - 54
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 1
ER -