Risk of ESRD and Mortality Associated With Change in Filtration Markers

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.

Observational analysis of 2 clinical trials.

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).

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.

ESRD and all-cause mortality.

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.

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).

Small sample size.

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.