Relation Between Kidney Function, Proteinuria, and Adverse Outcomes

CONTEXT: The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. OBJECTIVE: To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction, and progression to kidney failure. RESULTS: The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 95% CI, 6.6-7.8 vs 2.9 95% CI, 2.7-3.0 per 1000 person-years, respectively; rate ratio, 2.5 95% CI, 2.3-2.7). Similar results were observed when proteinuria was measured by ACR (15.9 95% CI, 14.0-18.1 and 7.0 95% CI, 6.4-7.6 per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 95% CI, 2.0-2.6) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. CONCLUSION: The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.