title: Higher estimated glomerular filtration rates may be associated with increased risk of adverse outcomes, especially with concomitant proteinuria.
abstract: The estimated glomerular filtration rate (eGFR) is a powerful predictor of adverse outcomes, but most attention has focused on studies in the setting of reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9 ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further, we tested whether concomitant proteinuria further increases the risk of outcomes among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it does for those with reduced eGFR. Using data from a population-based outpatient laboratory data set of 1,526,437 patients, we measured adjusted associations between eGFR calculated by the modification of diet in renal disease equation, urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2) (referent) and increased at both lower and higher levels of eGFR. Specifically, the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the referent group. Similar results were seen when the CKD-EPI equation (sensitivity analyses) was used to assess eGFR. Higher levels of eGFR were not associated with the risk of kidney failure or myocardial infarction. Thus, the presence and severity of proteinuria was significantly associated with graded increases in the risk of clinical outcomes for both lower and higher eGFR. We do not know, however, whether the finding at higher eGFR could be due to inadequacies of the eGFR formula at low serum creatinine levels.
authors.affiliation: Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada. mtonelli-admin@med.ualberta.ca
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.forename: Scott W
authors.initials: SW
authors.lastname: Klarenbach
authors.forename: Anita M
authors.initials: AM
authors.lastname: Lloyd
authors.forename: Matthew T
authors.initials: MT
authors.lastname: James
authors.forename: Aminu K
authors.initials: AK
authors.lastname: Bello
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Manns
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010045:Outpatients; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D011934:Reagent Strips; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation; D016482:Urinalysis / Q000295:instrumentation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011934:Reagent Strips; D003404:Creatinine