Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion

Background. The Kidney Disease Outcomes Quality Initiative guidelines aim to define chronic kidney disease (CKD) and classify its stages. Stage 3 CKD generally receives more attention than stage 1 or 2, because the more impaired glomerular filtration rate (GFR) in stage 3 suggests a higher cardiovascular and renal risk. In this study we evaluated cardiovascular and renal outcome in subjects with stage 1 and 2 CKD. For comparison, we also studied these outcomes in stage 3 CKD. Methods. We used data of 8495 subjects of the PREVEND study, a prospective community-based cohort study, with data on urinary albumin excretion (UAE) and serum creatinine available. As measure of cardiovascular outcome, combined cardiovascular morbidity and mortality was used. As renal outcome, mean annual change of estimated GFR (eGFR) was used. Results. 6905 subjects had no CKD; 243, 856 and 491 subjects had stage 1, 2 and 3 CKD, respectively. During a median follow-up of 7.5 years 565 cardiovascular events occurred. Incidence rates of cardiovascular events were higher (P < 0.001 for all groups) in subjects with stage 1-3 CKD (17.2, 22.2 and 20.9 events/1000 person-years, respectively) than in subjects without CKD (7.0 events/1000 person-years). Using subjects without CKD as reference, age- and sex-adjusted hazard ratios [HR (95% CI)] were 2.2 (1.5-3.3), 1.6 (1.3-2.0) and 1.3 (1.0-1.7), respectively. Compared to subjects without CKD but similar baseline eGFR, subjects with stage 1 or 2 CKD showed a larger decline in eGFR (-1.1 versus -1.5 and -0.2 versus -0.6 ml/min/1.73 m(2)/year, respectively, both P < 0.01). When subjects with stage 3 CKD were stratified according to the absence or presence of a UAE > 30 mg/24 h, age- and sex-adjusted HRs for CVD were 1.0 (0.7-1.4) and 1.6 (1.1-2.3) and the change in eGFR was 0.2 versus -0.3 ml/min/1.73 m(2)/year, respectively. Conclusion. Subjects with stage 1 or 2 CKD have an increased risk for adverse cardiovascular and renal outcome and should receive equal attention as subjects with stage 3 CKD. Subdividing stage 3 CKD according to the presence or absence of a UAE > 30 mg/24 h improves risk stratification within this stage.