Despite the high prevalence of chronic kidney disease (CKD), relatively few individuals with CKD progress to ESRD. A better understanding of the risk factors for progression could improve the classification system of CKD and strategies for screening. We analyzed data from 65,589 adults who participated in the Nord-Trøndelag Health (HUNT 2) Study (1995 to 1997) and found 124 patients who progressed to ESRD after 10.3 yr of follow-up. In multivariable survival analysis, estimated GFR (eGFR) and albuminuria were independently and strongly associated with progression to ESRD: Hazard ratios for eGFR 45 to 59, 30 to 44, and 15 to 29 ml/min per 1.73 m(2) were 6.7, 18.8, and 65.7, respectively (P < 0.001 for all), and for micro- and macroalbuminuria were 13.0 and 47.2 (P < 0.001 for both). Hypertension, diabetes, male gender, smoking, depression, obesity, cardiovascular disease, dyslipidemia, physical activity and education did not add predictive information. Time-dependent receiver operating characteristic analyses showed that considering both the urinary albumin/creatinine ratio and eGFR substantially improved diagnostic accuracy. Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min per 1.73 m(2)) would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referral based on our classification system would include 1.4% of the general population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to ESRD). In conclusion, all levels of reduced eGFR should be complemented by quantification of urinary albumin to predict optimally progression to ESRD.