Influence of urine creatinine on the relationship between the albumin-to-creatinine ratio and cardiovascular events

Clin J Am Soc Nephrol. 2012 Apr;7(4):595-603. doi: 10.2215/CJN.09300911. Epub 2012 Mar 1.

Abstract

Background and objectives: In the albumin-to-creatinine ratio (spot-ACR), urine creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass is associated with cardiovascular disease (CVD). We hypothesized that the spot-ACR would be higher in women, lower-weight persons, and older individuals, independent of timed urine albumin excretion (24hr-UAE), and accordingly, that spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these subgroups.

Design, setting, participants, & methods: 2627 PREVEND (Prevention of Renal and Vascular End-stage Disease) participants with 24hr-UAE <30 mg/d were followed for CVD events for 11 years. Cox regression evaluated associations of spot-ACR and 24hr-UAE with CVD events by sex, weight, and age.

Results: Female sex (26%), lower weight (2% per 5 kg), and older age (4% per 5 years) were associated with higher spot-ACR independent of 24hr-UAE (P<0.001). Spot urine albumin concentration (hazard ratio [HR], 1.26 per ln-SD higher) and 1/spot urine creatinine concentration (HR, 1.16 per ln-SD higher) were associated with CVD events. Spot-ACR was more strongly associated with CVD events than either component of the ratio (HR, 1.41 per ln-SD higher). Associations of spot-ACR ≥10 mg/g versus less (HR, 2.33) and 24hr-UAE ≥10 mg/d versus less (HR, 2.09) with CVD events were similar, and there were no significant differences across subgroups (P for interactions >0.06).

Conclusions: In community-living individuals with 24hr-UAE <30 mg/d, spot-ACR is higher in women, older persons, and lower-weight persons, independent of 24hr-UAE. Low spot urine creatinine is associated with CVD risk, but high urine albumin is a stronger determinant of the association of spot-ACR with CVD than is low urine creatinine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Albuminuria / diagnosis
  • Albuminuria / epidemiology*
  • Albuminuria / urine*
  • Biomarkers / urine
  • Body Weight
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / urine
  • Chi-Square Distribution
  • Creatinine / urine*
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Diseases / diagnosis
  • Kidney Diseases / epidemiology*
  • Kidney Diseases / urine*
  • Linear Models
  • Male
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Netherlands / epidemiology
  • Organ Size
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Time Factors

Substances

  • Biomarkers
  • Creatinine