title: Outcomes associated with microalbuminuria: effect modification by chronic kidney disease.
abstract: OBJECTIVE
  This study sought to compare the association of microalbuminuria with outcomes in patients with different comorbidities.
  
  
  BACKGROUND
  The risk of adverse outcomes associated with lower levels proteinuria has been found to be linearly decreasing with even low-normal levels of microalbuminuria. It is unclear whether comorbid conditions change these associations.
  
  
  METHODS
  We examined the association of urine microalbumin-creatinine ratio (UACR) with mortality and the slopes of estimated glomerular filtration rate (eGFR) in a nationally representative cohort of 298,875 U.S. veterans. Associations of UACR with all-cause mortality overall and in subgroups of patients with and without diabetes mellitus, hypertension, cardiovascular disease, congestive heart failure, and advanced chronic kidney disease (CKD) were examined in Cox models, and with the slopes of eGFR in linear and logistic regression models.
  
  
  RESULTS
  Very low levels of UACR were linearly associated with decreased mortality and less progression of CKD overall: adjusted mortality hazard ratio and estimated glomerular filtration rate slope (95% confidence interval [CI]) associated with UACR ≥200 μg/mg, compared to <5 μg/mg were 1.53 (95% CI: 1.38 to 1.69, p < 0.001) and -1.59 (95% CI: -1.83 to -1.35, p < 0.001). Similar linearity was present in all examined subgroups, except in patients with CKD in whom a U-shaped association was present and in whom a UACR of 10 to 19 was associated with the best outcomes.
  
  
  CONCLUSIONS
  The association of UACR with mortality and with progressive CKD is modified in patients with CKD, who experience higher mortality and worse progression of CKD with the lowest levels of UACR. Proteinuria-lowering interventions in patients with advanced CKD should be implemented cautiously, considering the potential for adverse outcomes.
authors.affiliation: Division of Nephrology, Memphis Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA. csaba.kovesdy@va.gov
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.forename: Evan H
authors.initials: EH
authors.lastname: Lott
authors.forename: Jun Ling
authors.initials: JL
authors.lastname: Lu
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Malakauskas
authors.forename: Jennie Z
authors.initials: JZ
authors.lastname: Ma
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000652:urine; D002423:Cause of Death; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000652:urine; D018450:Disease Progression; D015987:Effect Modifier, Epidemiologic; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000503:physiopathology / Q000652:urine; D012307:Risk Factors; D014481:United States