Change in novel filtration markers and risk of ESRD

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 (eGFR_cr) 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 eGFR_cr. 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 (eGFR_cr, cystatin C-based eGFR [eGFR_cys], 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 eGFR_cr. Results During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFR_cr, eGFR_cys, 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 eGFR_cr alone (HR, 31.97 [95% CI, 19.40-52.70; P = 0.03] vs eGFR_cr). 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.