Change in novel filtration markers and risk of ESRD

Casey M Rebholz, Morgan E Grams, Kunihiro Matsushita, Elizabeth Selvin, Josef Coresh
American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 2015, 66 (1): 47-54

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.


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.

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