End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined.

We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization.

The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m² of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m² (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m² (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m² (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m² (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern.

An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency.