Past Decline Versus Current eGFR and Subsequent ESRD Risk

Abstract

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).

Keywords: end-stage renal disease; epidemiology and outcomes; glomerular filtration rate; progression of chronic renal failure.

Figure 1.

Adjusted HR of ESRD associated with slope of eGFR during a 3-year baseline period and a histogram of the slope of eGFR in CKD cohorts. Values were trimmed at a −15-ml slope (0.3%) and a 10-ml slope (1.1%). Black dots indicate statistical significance compared with the reference (diamond) slope of eGFR=0 ml/min per 1.73 m² per year. Open circles show slope of eGFR=−6 and −3 ml/min per 1.73 m² per year.

Figure 2.

Adjusted relative HRs of ESRD for a 6-ml/min per 1.73 m² per year decline and a 3-ml/min per 1.73 m² per year decline in eGFR (compared with a decline of 0 ml/min per 1.73 m2 per year) during a 3-year baseline period in CKD cohorts. The left panel shows adjusted relative HRs for a 6-ml/min per 1.73 m² per year decline and the right panel shows adjusted relative HRs for a 3-ml/min per 1.73 m² per year decline. AASK, African American Study of Kidney Disease and Hypertension; BC CKD, British Columbia CKD Study; CCF, Cleveland Clinic CKD Registry Study; Geisinger, Geisinger CKD Study; GLOMMS1, Grampian Laboratory Outcomes, Morbidity and Mortality Studies 1; MASTERPLAN, Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner; MDRD, Modification of Diet in Renal Disease Study; NephroTest, NephroTest Study; Sunnybrook, Sunnybrook Cohort; VA CKD, Veterans Administration CKD Study.

Figure 3.

Adjusted HRs (95% CIs; reference: patients with eGFR=50 ml/min per 1.73 m² and slope of 0 ml/min per 1.73 m² per year) and absolute risks of ESRD associated with slope of eGFR and different levels of last eGFR during a 3-year baseline period in CKD cohorts. Panel A shows the adjusted HRs and panel B shows the absolute risks.